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Sample records for trolox ameliorates 3-nitropropionic

  1. The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats.

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    Mahdy, Heba M; Tadros, Mariane G; Mohamed, Mohamed R; Karim, Amr M; Khalifa, Amani E

    2011-11-01

    3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase enzyme (SDH), induces neurodegeneration similar to that observed in Huntington's disease (HD). Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity, bilateral striatal lesions as well as brain oxidative stress are major features of HD. The present study was designed to investigate neuroprotective effect of Ginkgo biloba extract (EGb 761) on 3-NP induced neurobehavioral changes and striatal lesions. Rats administered 3-NP (20mg/kg, s.c.) for five consecutive days exhibited PPI deficits and locomotor hypoactivity whereas, pretreatment of animals with EGb 761 (100mg/kg, i.p. for 15 days) ahead of and during the induction of HD by 3-NP (20mg/kg for 5 days starting at day 8) ameliorated 3-NP-induced neurobehavioral deficits. Administration of 3-NP increased the level of striatal malondialdehyde (MDA). This effect was prevented in animals pre-treated with EGb 761. Changes in the level of apoptotic regulatory gene expressions, following 3-NP treatment, were demonstrated as both an up-regulation and a down-regulation of the expression levels of striatal Bax and Bcl-xl genes, respectively. In addition, an up-regulation of the expression level of striatal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also observed. Pre-treatment with EGb 761 caused a down-regulation in striatal GAPDH and Bax together with an up-regulation of striatal Bcl-xl expression level as compared to the 3-NP treated group. Histochemical examination of striatal tissue showed that EGb 761 significantly prevented 3-NP induced inhibition of SDH activity. Histopathological examination further affirmed the neuroprotective effect of EGb 761 against 3-NP toxicity. Taken together, these results suggest that EGb 761 has a neuroprotective role in the current HD paradigm, which may be related to improvement of energy metabolism, antioxidant properties and antiapoptotic effects. Copyright

  2. Beneficial effect of rice bran extract against 3-nitropropionic acid induced experimental Huntington's disease in rats

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    Navneet Kaur

    2015-01-01

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, characterized by progressive motor and non-motor dysfunction due to degeneration of medium spiny neurons in striatum. 3-Nitropropionic acid is commonly used to induce the animal model of HD. Rice bran is supposed to have beneficial effects on mitochondrial function. The present study has been designed to explore the effect of rice bran extract against 3-Nitropropionic acid induced neurotoxicity in rats. 3-Nitropropionic acid (10 mg/kg, i.p was administered systemically for 21 days. Hexane and ethanol extract of rice bran were prepared using Soxhlation. Hexane (250 mg/kg and ethanol extract (250 mg/kg were administered per os for 21 days in 3-NP treated groups. Behavioral parameters (body weight, grip strength, motor coordination, locomotion were conducted on 7th, 14th and 21st day. Animals were sacrificed on 22nd day for biochemical, mitochondrial dysfunction (Complex II, neuroinflammatory and neurochemical estimation in striatum. This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration and decreased glutathione, mitochondrial function (decreased Complex II enzyme activity, pro-inflammatory mediators and neurochemical levels in 3-nitropropionic acid treated animals. Administration of hexane and ethanol extract prevented the behavioral, biochemical, neuroinflammatory (increased TNF-α, IL-1β and IL-6 and neurochemical alterations (decreased dopamine, norepinephrine, serotonin, 5-hydroxy indole acetic acid, GABA and increased 3,4-dihydro phenyl acetaldehyde, homovanillic acid and glutamate levels induced by 3-nitropropionic acid. The outcomes of present study suggest that rice bran extract is beneficial and might emerge as an adjuvant or prophylactic therapy for treatment of HD like symptoms.

  3. 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate

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    Storgaard, J; Kornblit, B T; Zimmer, J

    2000-01-01

    Mitochondrial inhibition by 3-nitropropionic acid (3-NPA) causes striatal degeneration reminiscent of Huntington's disease. We studied 3-NPA neurotoxicity and possible indirect excitotoxicity in organotypic striatal and corticostriatal slice cultures. Neurotoxicity was quantified by assay...

  4. Raw data of the effects of Chlorogenic acid in 3-Nitropropionic acid induced toxicity and genotoxicity

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    Alarcón-Herrera Norberto

    2017-10-01

    Full Text Available The raw data showed in this article comes from the published research article entitled “Protective effects of Chlorogenic acid in 3-Nitropropionic acid induced toxicity and genotoxicity” Food Chem Toxicol. 2017 May 3. pii: S0278-6915(1730226-0. DOI:10.1016/j.fct.2017.04.048. [1]. Data illustrates antitoxic and antigenotoxic effects of Chlorogenic acid (CGA on toxicity and genotoxicity produced by the in vivo treatment with mitochondria toxin 3-Nitropropionic acid (3-NP in mice. Toxicity and genotoxicity was evaluated in erythrocytes of peripheral blood through the micronuclei assay. Data was share at the Elsevier repository under the reference number FCT9033.

  5. Metabolic alterations produced by 3-nitropropionic acid in rat striata and cultured astrocytes: quantitative in vitro 1H nuclear magnetic resonance spectroscopy and biochemical characterization

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    Chang, C.; Wan, Y.L.; Goh, C.C.; Tsai, M.J.

    1997-01-01

    Quantitative high resolution in vitro 1 H nuclear magnetic resonance spectroscopy was employed to study the metabolic effects of 3-nitropropionic acid associated with aging from perchloric acid extracts of rat striata. Systemic injection of 3-nitropropionic acid in rats at a dose of 10 mg/kg/day for seven consecutive days significantly impaired energy metabolism in rats one, four and eight months of age, as evidenced by a marked elevation of succinate and lactate levels. However, a significant decrease in N-acetyl-l-aspartate level, a neuronal marker, was observed in four- and eight-month-old rats but not in one-month-old rats. This would indicate that rats at four to eight months are more susceptible to 3-nitropropionic acid than those at one month. A significant decrease in GABA level was observed in four-month-old 3-nitropropionic acid-treated rats, which is consistent with the literature that GABAergic neurons are particularly vulnerable to 3-nitropropionic acid treatment. In addition, glutamine and glutamate levels were markedly decreased at four and eight months in 3-nitropropionic acid-treated rats. Since glutamine is synthesized predominantly in glia, the observation above suggests that 3-nitropropionic acid intoxication may involve perturbation of energy metabolism, glial injury and consequent neuronal damage. Astrocytes which are essential in the metabolism of glutamate and glutamine were used to further assess 3-nitropropionic acid-induced toxicity. Glial proliferation, mitochondrial metabolism and glutamine synthetase activity were all reduced by 3-nitropropionic acid treatment with a concomitant increase, in a dose-dependent manner, of lactate levels, suggesting that 3-nitropropionic acid is also detrimental to astrocytes in vivo and thus may affect metabolic interaction between neurons and glia.These results not only imply that 3-nitropropionic acid blocks energy metabolism prior to exerting neurotoxic damage but also demonstrate that the degree of

  6. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

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    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

  7. Hyperactivity and hypoactivity in a rat model of Huntington's disease: the systemic 3-nitropropionic acid model.

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    Borlongan, C V; Koutouzis, T K; Freeman, T B; Hauser, R A; Cahill, D W; Sanberg, P R

    1997-08-01

    The present study proposes the use of systemic 3-nitropropionic acid (3-NP) treatment in rats as a model of Huntington's disease (HD). The systemic 3-NP model involves chronic injection of low dose intraperitoneal (i.p.) injections of 3-NP to rats once every 4 days over a period of time. Evidence from our experimental studies suggests that manipulating the number of injections can result in either increased nocturnal spontaneous locomotor activity (hyperactivity) or nocturnal akinesia (hypoactivity) [1]. For example, two injections of 3-NP (using the treatment of one injection every 4 days) result in hyperactivity, while four injections or more of 3-NP lead to hypoactivity [1]. The locomotor activity is recorded by Digiscan locomotor activity monitors [11]. The observation of these two types of locomotor activity is unique since no excitotoxin model has replicated a two-stage progression of a HD-like behavioral alteration. Most studies using excitotoxins like quinolinic acid (QA) and kainic acid (KA) have only reproduced the hyperactivity stage [4,5,7]. With the systemic 3-NP model, investigations into at least two stages of the disease are made possible. This allows for better assessment of intervention strategies such as neural transplants across different stages of the disease. The systemic 3-NP rat model is believed to be an improved animal model of HD.

  8. Neuroprotective potential of antioxidant potent fractions from Convolvulus pluricaulis Chois. in 3-nitropropionic acid challenged rats.

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    Kaur, Mandeep; Prakash, Atish; Kalia, Ajudhia Nath

    2016-01-01

    To isolate the neuroprotective component from Convolvulus pluricaulis Chois. (Convolvulaceae) which can be used as a lead molecule in the treatment of Huntington's disease (HD). The methanolic extract of whole plant was fractionated into four fractions; chloroform, ethyl acetate, n-butanol, and aqueous fraction. The chloroform and ethyl acetate fractions were pooled on the basis of antioxidant activity and TLC profile and charged into silica gel column. Four subfractions were collected from column (FrA, FrB, FrC, and FrD) and further assessed for antioxidant potential by 2,2-diphenyl-1-picrylhydrazyl in vitro assay. 3-Nitropropionic acid (3-NP) was administered to Wister rats for induction of HD. Different fractions were administered for 14 days. Different behavioral alterations were assessed in between study period. Animals were euthanized immediately following the last behavioral session, and biochemical parameters were measured. Systemic administration of 3-NP showed marked motor deficits and oxidative damage in rats. Only FrB showed significant antioxidant activity and on further purification gave pure compound (scopoletin). Our study showed that FrB (20 mg/kg) pre-treatment significantly attenuated the loss in body weight, improved the locomotor activity, grip strength, and gait abnormalities. It also has attenuated the increased malondialdehyde and nitrite levels, and restored superoxide dismutase and reduced GSH enzyme activity in the striatum and cortex in 3-NP-treated groups. These results suggest that C. pluricaulis Chois. exhibits a neuroprotective effect by accelerating brain antioxidant defense mechanisms in 3-NP-treated rats.

  9. Lithium chloride could aggravate brain injury caused by 3-nitropropionic acid

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    Aleksandra Milutinović

    2016-11-01

    Full Text Available Lithium, a well-known drug for the treatment of bipolar disorder, may also have the ability to reduce neurodegeneration and stimulate cell proliferation. Systemic injection of mitochondrial toxin 3-nitropropionic acid (3NPA is known to induce a relatively selective, Huntington disease-like brain injury. The aim of this study was to determine the effect of lithium chloride (LiCl on brain injury caused by 3NPA. Female adult Wistar rats were pre-treated with LiCl (127 mg/kg 1 day before the first injection of 3NPA (28 mg/kg, and then for 8 days with the same treatment but receiving LiCl 1 hour before 3NPA. Control groups were pre-treated accordingly, with LiCl or with normal saline, but were not treated with 3NPA. Staining for cytochrome c oxidase activity and in situ hybridization autoradiography of synaptotagmin-4 and -7 mRNAs were used to evaluate brain injury caused by 3NPA. There was a significant reduction of body weight in the 3NPA+LiCl group (79% compared to the 3NPA group (90%, p = 0.031 and both control groups (100%, p = 0.000. Densitometric evaluation of cytochrome c oxidase staining and in situ hybridization autoradiograms revealed that the pre-treatment with LiCl caused an increase in striatal lesion for about 40% (p = 0.049. Moreover, the lesion was observed also in the hippocampus of three animals from the 3NPA+LiCl group and in two animals from the 3NPA group. However, there were no differences between the LiCl and saline group in any of the measured parameters. We concluded that the pre-treatment with a relatively nontoxic dose of LiCl could aggravate brain injury caused by 3NPA.

  10. Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

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    Alejandro Silva-Palacios

    2017-08-01

    Full Text Available The brain is a very susceptible organ to structural and functional alterations caused by oxidative stress and its vulnerability increases with age. Understanding the antioxidant response activated by the transcription factor Nrf2 has become very important in the aging field in order to activate cellular protection. However, the role of Nrf2 inducers during old age has not been completely understood. Our aim was to activate the Nrf2 pathway by pre-treating old rats with a widely used Nrf2-inducer, tert-buthylhydroquinone (tBHQ, prior to 3-nitropropionic acid (3-NP insult, in order to evaluate its effects at a behavioral, morphological and biochemical levels. 3-NP has been used to reproduce the biochemical and pathophysiological characteristics of Huntington's disease due to an oxidative effect. Our results suggest that tBHQ confers an important protective effect against 3-NP toxicity; nevertheless, Nrf2 seems not to be the main protective pathway associated to neuroprotection. Hormetic responses include the activation of more than one transcription factor. Nrf2 and NFκB are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NFκB nuclear accumulation was also evaluated. Keywords: Aging, Nrf2 signaling, Tert-Buthylhydroquinone, Oxidative stress, 3-Nitropropionic acid

  11. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

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    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

  12. Protective effect of Calendula officinalis Linn. flowers against 3-nitropropionic acid induced experimental Huntington's disease in rats.

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    Shivasharan, B D; Nagakannan, Pandian; Thippeswamy, Boreddy Shivanandappa; Veerapur, Veeresh Prabakar; Bansal, Punit; Unnikrishnan, Mazhuvancherry K

    2013-10-01

    Oxidative stress (OS) and nitric oxide mechanisms have been recently proposed in 3-nitropropionic acid (3-NP)-induced neurotoxicity. The compounds, having antioxidant, anti-inflammatory and estrogenic effects, have been suggested for neuroprotection in different experimental models. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant, anti-inflammatory, estrogenic and neuroprotective activities. Hence, the present study was designed to evaluate the neuroprotective effect of COE on 3-NP-induced neurotoxicity in rats by observing behavioral changes, OS and striatal damage in rat brain. Adult female Wistar rats were pretreated with vehicle or COE (100 and 200 mg/kg) for 7 days, followed by cotreatment with 3-NP (15 mg/kg, intraperitoneally) for the next 7 days. At the end of the treatment schedule, rats were evaluated for alterations in sensory motor functions and short-term memory. Animals were sacrificed and brain homogenates were used for the estimation of lipid peroxidation (LPO), glutathione, total thiols, glutathione S-transferase, catalase and nitrite. A set of brain slices was used for the evaluation of neuronal damage in the striatal region of the brain. 3-NP caused significant alterations in animal behavior, oxidative defense system evidenced by raised levels of LPO and nitrite concentration, and depletion of antioxidant levels. It also produced a loss of neuronal cells in the striatal region. Treatment with COE significantly attenuated behavioral alterations, oxidative damage and striatal neuronal loss in 3-NP-treated animals. The present study shows that COE is protective against 3-NP-induced neurotoxicity in rats. The antioxidant, anti-inflammatory and estrogenic properties of COE may be responsible for its neuroprotective action.

  13. Protective effect of Convolvulus pluricaulis standardized extract and its fractions against 3-nitropropionic acid-induced neurotoxicity in rats.

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    Malik, Jai; Choudhary, Sunayna; Kumar, Puneet

    2015-01-01

    Convolvulus pluricaulis Chois. (Convolvulaceae), a well-known Ayurvedic "Medhya Rasayana" (nervine tonic), is extensively used for different central nervous system (CNS) disorders. The objective of this study was to evaluate the protective effect of standardized hydro-methanol extract of C. pluricaulis (CPE) and its fractions, namely ethyl acetate (EAE), butanol (BE), and aqueous (AE), against 3-nitropropionic acid (3-NP) induced neurotoxicity in rats. The extract of the whole plant was standardized on the basis of scopoletin content (0.014%) using thin layer chromatography densitometric analysis. CPE (100 and 200 mg/kg) and its fractions, namely EAE (15 and 30 mg/kg), BE (25 and 50 mg/kg), and AE (50 and 100 mg/kg) were administered orally for 20 d. Their protective effect against 3-NP (10 mg/kg, i.p. for 14 d) was assessed by the effect on various behavioral parameters, namely body weight, locomotor activity, grip strength, gait pattern, and the effect on cognitive dysfunction. Biochemical parameters for oxidative damage were also assessed in the striatum and cortex regions of the brain. Administration of 3-NP induced HD-like symptoms that were indicated by reduced body weight, locomotor activity, memory, grip strength, and oxidative defense. CPE (200 mg/kg), EAE (30 mg/kg), and BE (50 mg/kg) significantly (p < 0.001) attenuated 3-NP induced reduction in locomotor activity, grip strength, memory, body weight, and oxidative defense in comparison with 3-NP-treated animals on 10 and 15 d. The present study suggested that CPE has a protective action against 3-NP-induced neurotoxicity and can be further explored for its efficacy against Huntington's disease.

  14. Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity

    International Nuclear Information System (INIS)

    Ahuja, Manuj; Bishnoi, Mahendra; Chopra, Kanwaljit

    2008-01-01

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of the electron transport enzyme succinate dehydrogenase, a mitochondrial Complex II enzyme. Minocycline is a semi-synthetic second-generation tetracycline with neuroprotective activity and has the capability to effectively cross the blood-brain barrier. We investigated the effects of minocycline on behavioral, biochemical, inflammation related and neurochemical alterations induced by the sub-chronic administration of 3-nitropropionic acid to rats. Chronic pre-administration of minocycline (50 and 100 mg/kg) dose dependently prevented 3-NP-induced dysfunction behavioral (hypoactivity, memory retention, locomotor and rota-rod activity). In addition, 3-NP produced a marked increase in lipid peroxidation levels whereas decreased the activities of catalase and succinate dehydrogenase. In contrast, pretreatment of 3-NP injected rats with minocycline resulted in the attenuation of all these alterations. A marked increase in an inflammatory cytokine TNF-α by 3-NP was also decreased by minocycline treatment. Neurochemically, the administration of 3-NP significantly decreased the levels of catecholamines in the brain homogenates (dopamine, norepinephrine and serotonin) which were reversed by pretreatment of minocycline. The present finding explains the neuroprotective effect of minocycline against 3-NP toxicity by virtue of its antioxidant and anti-inflammatory activity

  15. Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells.

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    Kulasekaran, Gopinath; Ganapasam, Sudhandiran

    2015-11-01

    Oxidative stress and mitochondrial dysfunction are implicated in neuronal apoptosis associated with Huntington's disease. Naringin is the flavanone present in grapefruit and related citrus species possess diverse pharmacological and therapeutic properties including antioxidant, anti-apoptotic, and neuroprotective properties. The aim of this study was to investigate the protective effect of naringin on 3-nitropropionic acid (3-NP)-induced neurotoxicity in pheochromocytoma cells (PC12) cells and to explore its mechanism of action. Naringin protects PC12 cells from 3-NP neurotoxicity, as evaluated the by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione. The increase in levels of reactive oxygen species and lipid peroxidation induced by 3-NP were significantly decreased by naringin. PC12 cells induced with 3-NP showed decrease in the mitochondrial membrane potential and mitochondrial respiratory complex enzymes, succinate dehydrogenase and cytochrome c oxidase activities, and it was significantly altered to near normal upon naringin treatment. Naringin reduced the 3-NP-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 and Bcl-2-associated X protein. Further, naringin enhances the nuclear translocation of Nrf2 and induces the quinone oxidoreductase-1 and Heme oxygenase-1 expressions through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Taken together, the above findings suggest that naringin augments cellular antioxidant defense capacity and reduces the 3-NP-induced neurotoxicity in PC12 cells through the PI-3K/Akt-dependent Nrf2 activation in PC12 cells.

  16. Pomegranate seed oil: Effect on 3-nitropropionic acid-induced neurotoxicity in PC12 cells and elucidation of unsaturated fatty acids composition.

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    Al-Sabahi, Bushra N; Fatope, Majekodunmi O; Essa, Musthafa Mohamed; Subash, Selvaraju; Al-Busafi, Saleh N; Al-Kusaibi, Fatma S M; Manivasagam, Thamilarasan

    2017-01-01

    Seed oils are used as cosmetics or topical treatment for wounds, allergy, dandruff, and other purposes. Natural antioxidants from plants were recently reported to delay the onset or progress of various neurodegenerative conditions. Over one thousand cultivars of Punica granatum (Punicaceae) are known and some are traditionally used to treat various ailments. The effect of pomegranate oil on 3-nitropropionic acid- (3-NP) induced cytotoxicity in rat pheochromocytoma (PC12) neuronal cells was analyzed in this study. Furthermore, the analysis of unsaturated fatty acid composition of the seed oil of pomegranate by gas chromatography-electron impact mass spectrometry (GC-MS) was done. GC-MS study showed the presence of 6,9-octadecadiynoic acid (C18:2(6,9)) as a major component (60%) as 4,4-dimethyloxazoline derivative. The total extractable oil with light petroleum ether by Soxhlet from the dry seed of P. granatum was 4-6%. The oil analyzed for 48.90 ± 1.50 mg gallic acid equivalents/g of oil, and demonstrated radical-scavenging-linked antioxidant activities in various in vitro assays like the DPPH (2,2-diphenyl-l-picrylhydrazyl, % IP = 35.2 ± 0.9%), ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), % IP 2.2 ± 0.1%), and β-carotene bleaching assay (% IP = 26 ± 3%), respectively, which could be due the possible role of one methylene interrupted diynoic acid system for its radical-scavenging/antioxidant properties of oil. The oil also reduced lipid peroxidation, suppressed reactive oxygen species, extracellular nitric oxide, lactate/pyruvate ratio, and lactase dehydrogenase generated by 3-NP- (100 mM) induced neurotoxicity in PC12 cells, and enhanced the levels of enzymatic and non-enzymatic antioxidants at 40 μg of gallic acid equivalents. The protective effect of pomegranate seed oil might be due to the ability of an oil to neutralize ROS or enhance the expression of antioxidant gene and the exact mechanism of action yet to be elucidated.

  17. Systemic radical scavenger treatment of a mouse model of Rett syndrome: merits and limitations of the vitamin E derivative Trolox

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    Oliwa Alicja Janc

    2016-11-01

    Full Text Available Rett syndrome (RTT is a severe neurodevelopmental disorder typically arising from spontaneous mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2 gene. The almost exclusively female Rett patients show an apparently normal development during their first 6-18 months of life. Subsequently, cognitive- and motor-impairment, hand stereotypies, loss of learned skills, epilepsy, and irregular breathing manifest. Early mitochondrial impairment and oxidative challenge are considered to facilitate disease progression. Along this line, we recently confirmed in vitro that acute treatment with the vitamin E-derivative Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, ameliorates cellular redox balance, and improves hypoxia tolerance in male MeCP2-deficient (Mecp2-/y mouse hippocampus. Pursuing these promising findings, we performed a preclinical study to define the merit of systemic Trolox administration. Blinded, placebo-controlled in vivo treatment of male mice started at postnatal day 10-11 and continued for ~40 days. Compounds (vehicle only, 10 mg/kg or 40 mg/kg Trolox were injected intraperitoneally every 48h. Detailed phenotyping revealed that in Mecp2-/y mice, blood glucose levels, lipid peroxidation, synaptic short-term plasticity, hypoxia tolerance, and certain forms of environmental exploration were improved by Trolox. Yet, body weight and size, motor function, and the rate and regularity of breathing did not improve. In conclusion, in vivo Trolox treatment partially ameliorated a subset of symptoms of the complex Rett phenotype, thereby confirming a partial merit of the vitamin E-derivative based pharmacotherapy. Yet, it also became evident that frequent animal handling and the route of drug administration are critical issues to be optimized in future trials.

  18. Moderate Dose of Trolox Preventing the Deleterious Effects of Wi-Fi Radiation on Spermatozoa In vitro through Reduction of Oxidative Stress Damage.

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    Ding, Shang-Shu; Sun, Ping; Zhang, Zhou; Liu, Xiang; Tian, Hong; Huo, Yong-Wei; Wang, Li-Rong; Han, Yan; Xing, Jun-Ping

    2018-02-20

    The worsening of semen quality, due to the application of Wi-Fi, can be ameliorated by Vitamin E. This study aimed to demonstrate whether a moderate dose of trolox, a new Vitamin E, inhibits oxidative damage on sperms in vitro after exposure to Wi-Fi radiation. Each of the twenty qualified semen, gathered from June to October 2014 in eugenics clinic, was separated into four aliquots, including sham, Wi-Fi-exposed, Wi-Fi plus 5 mmol/L trolox, and Wi-Fi plus 10 mmol/L trolox groups. At 0 min, all baseline parameters of the 20 samples were measured in sequence. Reactive oxygen species, glutathione, and superoxide dismutase were evaluated in the four aliquots at 45 and 90 min, as were sperm DNA fragments, sperm mitochondrial potential, relative amplification of sperm mitochondrial DNA, sperm vitality, and progressive and immotility sperm. The parameters were analyzed by one-way analysis of variance and Tukey's posttest. Among Wi-Fi plus 5 mmol/L trolox, Wi-Fi-exposed and Wi-Fi plus 10 mmol/L trolox groups, reactive oxygen species levels (45 min: 3.80 ± 0.41 RLU·10 -6 ·ml -1 vs. 7.50 ± 0.35 RLU·10 -6 ·ml -1 vs. 6.70 ± 0.47 RLU·10 -6 ·ml -1 , P electromagnetic radiation-induced oxidative stress.

  19. 3-Nitropropionic Acid is a Suicide Inhibitor of MitochondrialRespiration that, Upon Oxidation by Complex II, Forms a Covalent AdductWith a Catalytic Base Arginine in the Active Site of the Enzyme

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    Huang, Li-shar; Sun, Gang; Cobessi, David; Wang, Andy C.; Shen,John T.; Tung, Eric Y.; Anderson, Vernon E.; Berry, Edward A.

    2005-12-01

    We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. 1.3.5.1) at up to 2.1 {angstrom} resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg297 as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg297. The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg 297 to be increased by 83 Da and to have potential of losing 44 Da, consistent with decarboxylation, during fragmentation.

  20. Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3-Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse Model of Huntington's Disease.

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    Skillings, Elizabeth A; Morton, A Jennifer

    2016-01-01

    Impairments in energy metabolism are implicated in Huntington's disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of HD patients, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients. Chemical preconditioning with 3-nitropropionic acid (3-NP), an irreversible inhibitor of SDH, has been shown to increase tolerance against experimental hypoxia in both heart and brain. Here we studied the effect of chronic preconditioning in the R6/2 mouse model of HD using mice carrying CAG repeat lengths of either 250 or 400 repeats. Both are transgenic fragment models, with 250CAG mice having a more rapid disease progression than 400CAG mice. Low doses of 3-NP (24 mg/kg) were administered via the drinking water and the effect on phenotype progression and cognition function assessed. After 3-NP treatment there were significant improvements in all aspects of the behavioural phenotype, apart from body weight, with timing and magnitude of improvements dependent on both CAG repeat length and sex. Specifically, a delay in the deterioration of general health (as shown by delayed onset of glycosuria and increased survival) was seen in both male and female 400CAG mice and in female 250CAG mice and was consistent with improved appearance of 3-NP treated R6/2 mice. Male 250CAG mice showed improvements but these were short term, and 3-NP treatment eventually had deleterious effects on their survival rate. When cognitive performance of 250CAG mice was assessed using a two-choice discrimination touchscreen task, we found that female mice showed significant improvements. Together, our results support the idea that energy metabolism contributes to the pathogenesis of HD, and suggest that improving energy deficits might be a therapeutically useful target.

  1. Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation: A multivariate approach.

    Science.gov (United States)

    Çelik, Ecem Evrim; Rubio, Jose Manuel Amigo; Andersen, Mogens L; Gökmen, Vural

    2017-12-15

    The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively and Trolox were used for this purpose. Experimental studies were carried out in autoxidizing liposome medium by monitoring the development of fluorescent products formed by lipid oxidation. Chemometric methods were used both at experimental design and multivariate data analysis stages. Comparison of the simple addition effects of Trolox and bound antioxidants with measured values on lipid oxidation revealed synergetic interactions for DF and refined olive oil-bound antioxidants, and antagonistic interactions for protein and extra virgin olive oil-bound antioxidants with Trolox. A generalized version of logistic function was successfully used for modelling the oxidation curve of liposomes. Principal component analysis revealed two separate phases of liposome autoxidation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Synthesis, structure, antioxidant activity, and water solubility of trolox ion conjugates

    Directory of Open Access Journals (Sweden)

    Yuliya V. Yushkova

    2018-01-01

    Full Text Available The interaction of trolox with ammonia, alkylamines of different classes, and amino derivatives of heterocyclic compounds, including nitroxyl radicals and alkaloids, led to the production of ammonium salts called ion conjugates (ICs. Five ICs were characterised by X-ray diffraction. This is the first time a wide range of ICs were made from trolox with amines, and ESI-MS data demonstrated they have the potential to generate pseudomolecular [(A−B+ + H]+ ions. For all obtained trolox ICs, a significant increase (1–3 orders of magnitude in water solubility was achieved while retaining high antioxidant activity. ICs synthesised from two biologically active fragments may be used to create polyfunctional agents with varying solubility and bioavailability.

  3. Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation

    DEFF Research Database (Denmark)

    Celik, Ecem Evrim; Amigo Rubio, Jose Manuel; Andersen, Mogens Larsen

    2017-01-01

    The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively...... of the simple addition effects of Trolox and bound antioxidants with measured values on lipid oxidation revealed synergetic interactions for DF and refined olive oil-bound antioxidants, and antagonistic interactions for protein and extra virgin olive oil-bound antioxidants with Trolox. A generalized version...

  4. Effect of trolox C on cardiac contracture induced by hydrogen peroxide

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    Belló-Klein A.

    1997-01-01

    Full Text Available Hydrogen peroxide (H2O2 perfused into the aorta of the isolated rat heart induces a positive inotropic effect, with cardiac arrhythmia such as extrasystolic potentiation or cardiac contractures, depending on the dose. The last effect is similar to the "stone heart" observed in reperfusion injury and may be ascribed to lipoperoxidation (LPO of the membrane lipids, to protein damage, to reduction of the ATP level, to enzymatic alterations and to cardioactive compounds liberated by LPO. These effects may result in calcium overload of the cardiac fibers and contracture ("stone heart". Hearts from male Wistar rats (300-350 g were perfused at 31oC with Tyrode, 0.2 mM trolox C, 256 mM H2O2 or trolox C + H2O2. Cardiac contractures (baseline elevation of the myograms obtained were observed when hearts were perfused with H2O2 (Tyrode: 5.9 ± 3.2; H2O2: 60.5 ± 13.9% of the initial value; perfusion with H2O2 increased the LPO of rat heart homogenates measured by chemiluminescence (Tyrode: 3,199 ± 259; H2O2: 5,304 ± 133 cps mg protein-1 60 min-1, oxygen uptake (Tyrode: 0.44 ± 0.1; H2O2: 3.2 ± 0.8 nmol min-1 mg protein-1 and malonaldehyde (TBARS formation (Tyrode: 0.12 ± 0; H2O2: 0.37 ± 0.1 nmol/ml. Previous perfusion with 0.2 mM trolox C reduced the LPO (chemiluminescence: 4,098 ± 531, oxygen uptake (0.51 ± 0 and TBARS (0.13 ± 0 but did not prevent the H2O2-induced contractures (33.3 ± 16%. ATP (Tyrode: 2.84 ± 0; H2O2: 0.57 ± 0 and glycogen levels (Tyrode: 0.46 ± 0; H2O2: 0.26 ± 0 were reduced by H2O2. Trolox did not prevent these effects (ATP: 0.84 ± 0 and glycogen: 0.27 ± 0. Trolox C is known to be more effective than a -tocopherol or g -tocopherol in reducing LPO though it lacks the phytol portion of vitamin E to be fixed to the cell membranes. Trolox C, unlike vitamin A, did not prevent the glycogen reduction induced by H2O2. Trolox C induced a positive chronotropic effect that resulted in higher energy consumption. The reduction of

  5. Quantitative and antioxidative behavior of Trolox in rats' blood and brain by HPLC-UV and SMFIA-CL methods.

    Science.gov (United States)

    Wada, Mitsuhiro; Wada, Misato; Ikeda, Rie; Fuchigami, Yuki; Koyama, Hironari; Ohkawara, Susumu; Kawakami, Shigeru; Kuroda, Naotaka; Nakashima, Kenichiro

    2016-03-01

    Trolox, a water-soluble vitamin E analogue has been used as a positive control in Trolox equivalent antioxidant capacity and oxygen radical antioxidant capacity assays due to its high antioxidative effect. In this study, the ex vivo antioxidative effects of Trolox and its concentration in blood and brain microdialysates from rat after administration were evaluated by newly established semi-microflow injection analysis, chemiluminescence detection and HPLC-UV. In the administration test, the antioxidative effect of Trolox in blood and brain microdialysates after a single administration of 200 mg/kg of Trolox to rats could be monitored. The antioxidative effects in blood (12.0 ± 2.1) and brain (8.4 ± 2.1, × 10(3) antioxidative effect % × min) also increased. Additionally, the areas under the curve (AUC)s0-360 (n = 3) for blood and brain calculated with quantitative data were 10.5 ± 1.2 and 9.7 ± 2.5 mg/mL × min, respectively. This result indicates that Trolox transferability through the blood-brain barrier is high. The increase in the antioxidative effects caused by Trolox in the blood and brain could be confirmed because good correlations between concentration and antioxidative effects (r ≥ 0.702) were obtained. The fact that Trolox can produce an antioxidative effect in rat brain was clarified. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Vitamin E (Trolox) addition to Tris-egg yolk extender preserves ram spermatozoon structure and kinematics after cryopreservation.

    Science.gov (United States)

    Silva, Sildivane Valcácia; Soares, Adriana Trindade; Batista, André Mariano; Almeida, Felipe Costa; Nunes, José Ferreira; Peixoto, Christina Alves; Guerra, Maria Madalena Pessoa

    2013-02-01

    Several studies reveal that vitamin E acts as a cellular stabilizer of unsaturated lipids against oxidative deterioration, thus maintaining structural and functional integrity at the subcellular level. The objective of this study was to evaluate Vitamin E (Trolox) addition to freezing extender for ram spermatozoa. Semen samples were diluted in Tris-yolk egg medium without antioxidant (control group) and with Trolox in different concentrations (30, 60 and 120μM). After thawing (37°C/30s), samples were subjected to analysis for plasma membrane integrity (PMi), acrosome integrity (Aci), mitochondrial membrane potential (MMP), sperm kinematics, and ultrastructural integrity. The Trolox 60 and 120μM groups showed higher percentages of iPMs (Pspermatozoon head plasma membranes, while for the spermatozoon tail, plasma membrane preservation at 60μM was higher (P<0.05) than the other groups. The Trolox 60 and 120μM groups presented more mitochondrial ultrastructural preservation than the other groups (P<0.05). These results indicate that Trolox addition to Tris-egg yolk at 60 and 120μM provides greater structural integrity (plasma membrane and mitochondria) and kinematics for ram spermatozoa after cryopreservation. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. 3-nitropropionic acid neurotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noer, Helle; Kristensen, Bjarne W; Noraberg, Jens

    2002-01-01

    : CA1 > CA3 > fascia dentata. In low glucose much lower concentrations of 3-NP (25 microM) triggered neurotoxicity. One-week-old cultures were less susceptible to 3-NP toxicity than 3-week-old cultures, but the dentate granule cells were relatively more affected in the immature cultures. We found...

  8. The predictive value of the antioxidant capacity of structurally related flavonoids using the Trolox equivalent antioxidant capacity (TEAC) assay

    NARCIS (Netherlands)

    Berg, R. van den; Haenen, G.R.M.M.; Berg, H. van den; Vijgh, W. van der; Bast, A.

    2000-01-01

    The antioxidant capacity of a series of structurally related flavonoids is quantified by the amount of ABTS [2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate)] radical anions (ABTS(.)-) that is able to react with the flavonoid and expressed as the Trolox equivalent antioxidant capacity (TEAC). To

  9. Applicability of an improved Trolox equivalent antioxidant capacity (TEAC) assay for evaluation of antioxidant capacity measurements of mixtures

    NARCIS (Netherlands)

    Berg, R. van den; Haenen, G.R.M.M.; Berg, H. van den; Bast, A.

    1999-01-01

    The TEAC (Trolox equivalent antioxidant capacity) assay is based on scavenging of 2,2'-azinobis-(3- ethylbenzothiazoline-6-sulfonate) radical anions (ABTS(.-)). In this report we describe a modification based on pre-generation of the ABTS radical anions with a thermolabile azo compound, 2,2'-azobis-

  10. Inclusion of bovine lipoproteins and the vitamin E analogue, Trolox, during in vitro culture of bovine embryos changes both embryo and fetal development.

    Science.gov (United States)

    Rooke, J A; Watt, R G; Ashworth, C J; McEvoy, T G

    2012-01-01

    This experiment investigated effects of lipoproteins and Trolox (vitamin E analogue) on bovine embryo and fetal development. The treatments were: in vitro culture (IVC) in synthetic oviducal fluid alone (SOF); with bovine lipoproteins (2% v/v; SOFLP); with Trolox (100μM; SOFT); and with lipoproteins and Trolox (SOFLPT). In vitro culture with lipoproteins increased fatty acid content of blastocysts (Peffect (P>0.05). Whereas lipoproteins reduced zygote development to blastocysts (P=0.03), Trolox facilitated increased development (P0.05) had no effect on blastocyst morphological grade. Pregnancy rates resulting from synchronous transfer of IVP embryos were not affected by IVC treatment. At Day 70 of pregnancy, compared with SOF, fetal weight was lower in SOFLP but not SOFLPT (interaction, Pembryo grades were also associated with increased numbers of placentomes (P=0.024). In conclusion, the interactive effects of lipoprotein and Trolox inclusion on in vitro embryo development were also evident in fetal development at Day 70.

  11. Thermochemistry of 2,2,5,7,8-pentamethylchroman-6-ol (PMC) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox)

    International Nuclear Information System (INIS)

    Bernardes, Carlos E.S.; Simões, Ricardo G.; Diogo, Hermínio P.; Minas da Piedade, Manuel E.

    2014-01-01

    Highlights: • We measured C p,m o (cr/g), Δ f H m o (cr/g), Δ fus H m o and Δ sub H m o for 2,2,5,7,8-pentamethylchroman-6-ol (PMC). • We measured C p,m o (cr/g), Δ f H m o (cr/g), Δ fus H m o and Δ sub H m o for 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox). • We found that, if present, an intramolecular hydrogen bond in trolox must be weak. • We found that the replacement of a CH 3 group in PMC by a COOH group in trolox approximately conforms to group additivity. - Abstract: 2,2,5,7,8-Pentamethylchroman-6-ol (PMC, CAS number 950-99-2) and 6-hydroxy-2,5,7,8-tetramethyl chroman-2-carboxylic acid (trolox, CAS number 53188-07-1) are perhaps the two most widely used model compounds for α-tocoferol, the main active antioxidant form of vitamin E. Because the antioxidant activity of α-tocoferol, and of phenol derivatives (ArOH) in general (such as PMC and trolox), is intimately related to the breaking of the ArO-H bond, considerable efforts have been made to investigate how the energetics of that bond is linked to the structure and energetics of both the ArO · radical and the ArOH parent compound, which are reflected by the corresponding enthalpies of formation. In this work the standard molar enthalpies of formation of crystalline PMC (triclinic, space group P1 ¯ phase) and trolox (monoclinic, space group P2 1 /c phase), at T = 298.15 K, were obtained as Δ f H m o (PMC,cr) = −(513.7 ± 3.4) kJ · mol −1 and Δ f H m o (trolox,crI) = −(892.5 ± 4.1) kJ · mol −1 by combustion calorimetry. The results of drop-sublimation Calvet microcalorimetry experiments and vapor pressure vs. temperature measurements by the Knudsen effusion method, combined with C p,m o (cr) and C p,m o (g) data obtained by differential scanning calorimetry and calculated at the B3LYP/6-31+G(d, p) level of theory, respectively, led to Δ sub H m o (PMC) = (107.4 ± 0.8) kJ · mol −1 and Δ sub H m o (trolox) = (136.9 ± 2.5) kJ · mol −1 at T = 298.15 K

  12. The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Oliwia Alicja Janc

    2014-02-01

    Full Text Available Rett syndrome (RS causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2-deficient mouse (Mecp2-/y hippocampus, confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance. As these changes may contribute to the manifestation of symptoms and disease progression, we now evaluated whether free radical scavengers are capable of improving neuronal and mitochondrial function in RS. Acute hippocampal slices of adult mice were incubated with the vitamin E derivative Trolox for 3-5 h. In Mecp2-/y slices this treatment dampened neuronal hyperexcitability, improved short-term plasticity, and fully restored synaptic long-term potentiation. Furthermore, Trolox specifically attenuated the increased hypoxia susceptibility of Mecp2-/y slices. Also, the anticonvulsive effects of Trolox were assessed, but the severity of 4-aminopyridine provoked seizure-like discharges was not significantly affected. Adverse side effects of Trolox on mitochondria can be excluded, but clear indications for an improvement of mitochondrial function were not found. Since several ion-channels and neurotransmitter receptors are redox modulated, the mitochondrial alterations and the associated oxidative burden may contribute to the neuronal dysfunction in RS. We confirmed in Mecp2-/y hippocampus that Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance. Therefore, radical scavengers are promising compounds for the treatment of neuronal dysfunction in RS and deserve further detailed evaluation.

  13. The Antioxidant Trolox Enhances the Oxidation of 2’,7’-Dichlorofluorescin to 2’, 7’-Dichlorofluorrescein

    Science.gov (United States)

    1997-01-01

    e.g., uric acid, TEMPOL ) either dichlorofluorescein (DCF). The formation of DCF have no effect or can increase levels of DCF. These can be followed...Radiobiology Research Institute’s 60 Co Chemical Co. (St. Louis, MO) with the exception of gamma radiation source at room temperature TEMPOL , which was obtained...oxi- dized DCFH-DA, although to a much lesser DISCUSSION extent than Trolox. Compounds that are free radicals (e.g., TEMPOL ) or can form stable radi

  14. Adição de piruvato de sódio e trolox ao diluidor utilizado para congelação de sêmen de garanhões férteis e subférteis Effect of pyruvate and trolox added to the extender used for freezing fertile and subfertile stallion semen

    Directory of Open Access Journals (Sweden)

    Karen Mascaro Gonçalves da Silva

    2008-11-01

    Full Text Available O objetivo deste trabalho foi avaliar o efeito do piruvato e trolox (forma solúvel da vitamina E sobre a qualidade espermática pós-descongelamento. Assim, com o intuito de proteger as células espermáticas dos efeitos deletérios da criopreservação,foram considerados os seguintes tratamentos: T1 (Controle= INRA82-HEPES sem antioxidantes; T2= INRA82-HEPES + 2mM de piruvato e T3= INRA82-HEPES + 120mM de trolox. As amostras de sêmen descongeladas foram avaliadas quanto à motilidade total (MT e progressiva (MP,a integridades de membrana plasmática e acrossômica, integridade do DNA, à estabilidade de membrana e ao potencial de membrana mitocondrial (Δψm. A adiηγo de piruvato proporcionou resultados superiores (PThe objective of this research was to evaluate the effect of pyruvate and trolox on the thawed sperm quality. For freezing, antioxidants were added to INRA 82-HEPES extender to protect sperm from the deleterious effects of oxidative stress, according to the treatments: T1= INRA82-HEPES without antioxidants; T2= INRA82-HEPES + 2mM of pyruvate and T3= INRA82-HEPES + 120 mM de trolox. The thawed semen samples were evaluated according to the total (MT and progressive (MP motility, integrity of plasma and acrossomal membrane, DNA integrity, membrane stability and mitochondrial membrane potential (Δψm. It was observed that the addition of pyruvate resulted in a significantly higher total sperm motility (P<0.05 to those obtained with trolox (9.17 and 14.5%, respectively. It can be concluded that the addition of pyruvate improves sperm motility (18.92 and 19.0%, respectively in samples from fertile and sub-fertile stallions submitted to freezing.

  15. EFEITO DA ADIÇÃO DE TROLOX E GLUTATIONA REDUZIDA NA VIABILIDADE in vitro DE ESPERMATOZOIDES DE CÃES

    Directory of Open Access Journals (Sweden)

    Paulo César Vasco de Albuquerque Peixoto

    2013-12-01

    Full Text Available In order to evaluate the effect of adding Trolox and Glutathione reduced antioxidants on the in vitro viability of dog cryopreserved sperm, semen samples were harvested from animals of French Bulldog (n=1, Basset Hound (n=2 and Rottweiler (n=1 breeds, through digital manipulation. After macroscopic and microscopic evaluation, the volume of semen was divided in aliquots, according to the experiments and experimental groups, using different concentrations of Trolox (200 and 300 mM/L or GSH (2 and 5 mM/L. The samples were packaged in straws (0.25 mL, cryopreserved in freezing machine and stored in liquid nitrogen. After thawing at 37 ºC (60 sec and incubation during 60 minutes, we verified that motility, vigor and sperm with intact acrosomes showed significant difference (P<0.05 only among incubation times, on the three experiments. In Exp. 2, the addition of 2 and 5 mM/L of GSH (G2 and G3 determined higher (P<0.05 percentage of sperm without oxidative stress. Therefore, we could conclude that GSH, on the concentration of 2 and 5 mM/L, can be added to diluent of dog semen cryopreservation.

  16. Efeito da adição de trolox e pentoxifilina na motilidade, integridade do acrossoma e do DNA de espermatozoides equinos após descongelação Effect of trolox and pentoxifylline on motility and integrity of, acrossome and DNA of equine spermatozoa after thawing

    Directory of Open Access Journals (Sweden)

    K.M.G. Silva

    2009-02-01

    Full Text Available Três garanhões foram utilizados para estudar o efeito da adição de trolox e pentoxifilina na motilidade, integridade do acrossoma e DNA de espermatozoides pós-descongelação. Para congelação, utilizou-se Tris-gema com glicerol (5% em máquina de congelação de sêmen. As amostras foram descongeladas a 37ºC durante 30 segundos e tratadas com: T1= 150µL de sêmen + 150µL de Tris; T2= 150µL de sêmen + 150µL de Tris + 120µM/mL de trolox; T3= 150µL de sêmen + 150µL de Tris + 3,5mM de pentoxifilina e T4= 150µL de sêmen + 150µL de Tris + 3,5mM de pentoxifilina + 120µM/mL de trolox. Após 0, 60 e 120 minutos de incubação (37ºC, as amostras foram analisadas quanto à motilidade, vigor, integridade de acrossoma e DNA. Não houve diferença (P>0,05 entre tratamentos após 0 e 60 minutos de incubação em todos os parâmetros estudados. Após 120 minutos de incubação, verificou-se maior porcentual (PThree stallions were used to study the effect of trolox and pentoxifylline addition on the motility and integrity of acrossome and DNA equine spermatozoa after thawing. Tris-egg-yolg diluent with glycerol (5% were used to freeze the semen samples in a freezing machine. The samples were thawed at 37ºC during 30 seconds and treated with: T1=150µL of semen + 150µL of Tris; T2= 150µL of semen + 150µL of Tris +150mM/mL of trolox; T3= 150µL of semen + 150µL Tris +3.5mM of pentoxifylline; and T4= 150µL of semen + 150µL of Tris + 3.5mM of pentoxifylline + 150mM of trolox. After 0, 60, and 120 minutes of incubation (37ºC, the samples were analyzed to motility, vigor, and integrity of acrossome and DNA. There was no difference (P>0.05 among treatments considering 0 and 60 minutes of incubation in all studied parameters. After 120 minutes of incubation, it was observed higher percentage (P<0.05 of cells with total and progressive motility in the samples of T2. It can be concluded that the trolox addition after thawing of equine semen

  17. Racemic crystals of trolox derivatives compared to their chiral counterparts: Structural studies using solid-state NMR, DFT calculations and X-ray diffraction

    Science.gov (United States)

    Wałejko, P.; Paradowska, K.; Szeleszczuk, Ł.; Wojtulewski, S.; Baj, A.

    2018-03-01

    Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) is a water-soluble vitamin E analogue that is available in enantiomeric forms R or S. Enantiomerically pure Trolox 1, its derivatives 2, 3 (R and S enantiomers) and racemic forms 1-3 were studied using solid-state 13C cross-polarisation (CP) magic angle spinning (MAS) NMR (13C CPMAS NMR). Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations of the shielding constants supported the assignment of 13C resonances in the solid-state NMR spectra. For the 13C CPMAS NMR spectra of 1, resonances of pure enantiomers were significantly broader than those of the racemic R/S form. In order to explain these effects, five of the available crystal structures were analysed (1R/S, 3R/S, 2S and the newly measured 2R/S and 3S). Cyclic dimers with one R and one S enantiomer linked by two OHsbnd Odbnd C2b hydrogen bonds were formed in 1R/S. Similar hydrogen-bonded dimers were present in 3S but not in 3R/S, in which interactions are water-mediated. A comparison of X-ray diffraction, CPMAS NMR data and the DFT GIPAW calculations of racemic forms and pure enantiomers was conducted for the first time. Our results, particularly the solid-state NMR data, were discussed in relation to Wallach's rule, that the racemic crystal appears as more ordered than its chiral counterpart.

  18. Polysulfides and products of H2S/S-nitrosoglutathione in comparison to H2S, glutathione and antioxidant Trolox are potent scavengers of superoxide anion radical and produce hydroxyl radical by decomposition of H2O2.

    Science.gov (United States)

    Misak, Anton; Grman, Marian; Bacova, Zuzana; Rezuchova, Ingeborg; Hudecova, Sona; Ondriasova, Elena; Krizanova, Olga; Brezova, Vlasta; Chovanec, Miroslav; Ondrias, Karol

    2018-06-01

    Exogenous and endogenously produced sulfide derivatives, such as H 2 S/HS - /S 2- , polysulfides and products of the H 2 S/S-nitrosoglutathione interaction (S/GSNO), affect numerous biological processes in which superoxide anion (O 2 - ) and hydroxyl (OH) radicals play an important role. Their cytoprotective-antioxidant and contrasting pro-oxidant-toxic effects have been reported. Therefore, the aim of our work was to contribute to resolving this apparent inconsistency by studying sulfide derivatives/free radical interactions and their consequent biological effects compared to the antioxidants glutathione (GSH) and Trolox. Using the electron paramagnetic resonance (EPR) spin trapping technique and O 2 - , we found that a polysulfide (Na 2 S 4 ) and S/GSNO were potent scavengers of O 2 - and cPTIO radicals compared to H 2 S (Na 2 S), GSH and Trolox, and S/GSNO scavenged the DEPMPO-OH radical. As detected by the EPR spectra of DEPMPO-OH, the formation of OH in physiological solution by S/GSNO was suggested. All the studied sulfide derivatives, but not Trolox or GSH, had a bell-shaped potency to decompose H 2 O 2 and produced OH in the following order: S/GSNO > Na 2 S 4  ≥ Na 2 S > GSH = Trolox = 0, but they scavenged OH at higher concentrations. In studies of the biological consequences of these sulfide derivatives/H 2 O 2 properties, we found the following: (i) S/GSNO alone and all sulfide derivatives in the presence of H 2 O 2 cleaved plasmid DNA; (ii) S/GSNO interfered with viral replication and consequently decreased the infectivity of viruses; (iii) the sulfide derivatives induced apoptosis in A2780 cells but inhibited apoptosis induced by H 2 O 2 ; and (iv) Na 2 S 4 modulated intracellular calcium in A87MG cells, which depended on the order of Na 2 S 4 /H 2 O 2 application. We suggest that the apparent inconsistency of the cytoprotective-antioxidant and contrasting pro-oxidant-toxic biological effects of sulfide derivatives results from their time

  19. An alternative standard for Trolox-equivalent antioxidant-capacity estimation based on thiol antioxidants. Comparative 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] decolorization and rotational viscometry study regarding hyaluronan degradation.

    Science.gov (United States)

    Hrabárová, Eva; Valachová, Katarína; Rapta, Peter; Soltés, Ladislav

    2010-09-01

    Comparison of the effectiveness of antioxidant activity of three thiol compounds, D-penicillamine, reduced L-glutathione, and 1,4-dithioerythritol, expressed as a radical-scavenging capacity based on the two independent methods, namely a decolorization 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] assay and a rotational viscometry, is reported. Particular concern was focused on the testing of potential free-radical scavenging effects of thiols against hyaluronan degradation, induced by hydroxyl radicals. A promising, solvent-independent, antioxidative function of 1,4-dithioerythritol, comparable to that of a standard compound, Trolox(®), was confirmed by the 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] assay. The new potential antioxidant 1,4-dithioerythritol exhibited very good solubility in a variety of solvents (e.g., H(2)O, EtOH, and DMSO) and could be widely accepted and used as an effective antioxidant standard instead of a routinely used Trolox(®) on 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] assay.

  20. Black ginseng extract ameliorates hypercholesterolemia in rats

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    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  1. Fucoidan Extracts Ameliorate Acute Colitis.

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available Inflammatory bowel diseases (IBD, such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy and depyrogenated fucoidan (DPF was evaluated in the dextran sulphate sodium (DSS mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF or intraperitoneal administration (DPF. Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could

  2. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

    Directory of Open Access Journals (Sweden)

    Meryam Debbabi

    2016-11-01

    Full Text Available Lipid peroxidation products, such as 7-ketocholesterol (7KC, may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA. Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

  3. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

    Science.gov (United States)

    Debbabi, Meryam; Nury, Thomas; Zarrouk, Amira; Mekahli, Nadia; Bezine, Maryem; Sghaier, Randa; Grégoire, Stéphane; Martine, Lucy; Durand, Philippe; Camus, Emmanuelle; Vejux, Anne; Jabrane, Aymen; Bretillon, Lionel; Prost, Michel; Moreau, Thibault; Ammou, Sofien Ben; Hammami, Mohamed; Lizard, Gérard

    2016-01-01

    Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases. PMID:27897980

  4. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    Science.gov (United States)

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC. Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  5. 27 CFR 24.178 - Amelioration.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Amelioration. 24.178 Section 24.178 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation and...

  6. Ameliorative effects of selenium and zinc

    African Journals Online (AJOL)

    Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. ... In contrast, reduced glutathione level (GSH), and the activities of catalase (CAT), superoxide dismutase (SOD), and the glutathione peroxidase (GPx) content of hepatic tissue decreased ...

  7. Ameliorative effect of Lentinus squarrosulus mycomeat against ...

    African Journals Online (AJOL)

    Ameliorative effect of Lentinus squarrosulus mycomeat against Pseudomonas aeruginosa infection using albino rat as animal model. ... The increasing awareness of inherent therapeutic and prophylactic benefits of some higher fungi and their products has been the recent trend for improving a healthy vigour. Mycomeat is a ...

  8. Amelioration of radiation nephropathy by acetylsalicylic acid

    NARCIS (Netherlands)

    Verheij, M.; Stewart, F. A.; Oussoren, Y.; Weening, J. J.; Dewit, L.

    1995-01-01

    This investigation was carried out to assess the amelioration by two antithrombotic drugs of radiation nephropathy in mice. Mouse kidneys were given split-dose irradiation to total doses between 17 and 22 Gy. A first group of animals was given acetylsalicylic acid (ASA) in drinking water, a second

  9. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  10. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress.

  11. The performance of maize crop during acid amelioration with ...

    African Journals Online (AJOL)

    Tanzania Journal of Science ... This study evaluated acid ameliorative potential and their effects on maize growth of four organic residues namely wild spikenard, cordia, cowpea and pigeon peas ... The finding suggests different acid ameliorating potential of residues, pigeon peas and cordia being the most effective.

  12. Use of Coffee Pulp and Minerals for Natural Soil Ameliorant

    Directory of Open Access Journals (Sweden)

    Pujiyanto Pujiyanto

    2007-05-01

    Full Text Available In coffee plantation, solid waste of coffee pulp is usually collected as heap nearby processing facilities for several months prior being used as compost. The practice is leading to the formation of odor and liquid which contaminate the environment. Experiments to evaluate the effect of natural soil ameliorant derived from coffee pulp and minerals were conducted at The Indonesian Coffee and Cocoa Research Institute in Jember, East Java. The experiments were intended to optimize the use of coffee pulp to support farming sustainability and minimize negative impacts of solid waste disposal originated from coffee cherry processing. Prior to applications, coffee pulp was hulled to organic paste. The paste was then mixed with 10% minerals (b/b. Composition of the minerals was 50% zeolite and 50% rock phosphate powder. The ameliorant was characterized for their physical and chemical properties. Agronomic tests were conducted on coffee and cocoa seedling. The experiments were arranged according to Randomized Completely Design with 2 factors, consisted of natural ameliorant and inorganic fertilizer respectively. Natural ameliorant derived from coffee pulp was applied at 6 levels: 0, 30, 60, 90, 120 and 150 g dry ameliorant/seedling of 3 kg soil, equivalent to 0, 1, 2, 3, 4 and 5% (b/b of ameliorant respectively. Inorganic fertilizer was applied at 2 levels: 0 and 2 g fertilizer/application of N-P-K compound fertilizer of 15-15-15 respectively. The inorganic fertilizer was applied 4 times during nursery of coffee and cocoa. The result of the experiment indicated that coffee pulp may be used as natural soil ameliorant. Composition of ameliorant of 90% coffee pulp and 10% of minerals has good physical and chemical characteristics for soil amelioration. The composition has high water holding capacity; cations exchange capacity, organic carbon and phosphorus contents which are favorable to increase soil capacity to support plant growth. Application of

  13. Improvement for Amelioration Inventory Model with Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Han-Wen Tuan

    2017-01-01

    Full Text Available Most inventory models dealt with deteriorated items. On the contrary, just a few papers considered inventory systems under amelioration environment. We study an amelioration inventory model with Weibull distribution. However, there are some questionable results in the amelioration paper. We will first point out those questionable results in the previous paper that did not derive the optimal solution and then provide some improvements. We will provide a rigorous analytical work for different cases dependent on the size of the shape parameter. We present a detailed numerical example for different ranges of the sharp parameter to illustrate that our solution method attains the optimal solution. We developed a new amelioration model and then provided a detailed analyzed procedure to find the optimal solution. Our findings will help researchers develop their new inventory models.

  14. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

    Directory of Open Access Journals (Sweden)

    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  15. Black ginseng extract ameliorates hypercholesterolemia in rats.

    Science.gov (United States)

    Saba, Evelyn; Jeon, Bo Ra; Jeong, Da-Hye; Lee, Kija; Goo, Youn-Kyoung; Kim, Seung-Hyung; Sung, Chang-Keun; Roh, Seong-Soo; Kim, Sung Dae; Kim, Hyun-Kyoung; Rhee, Man-Hee

    2016-04-01

    Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  16. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  17. The ameliorative effects of Moringa oleifera leaf extract on ...

    African Journals Online (AJOL)

    ADEYEYE

    2017-03-13

    Mar 13, 2017 ... *Correspondence: Tel.: +2348033858362; E-mail: misibisol@yahoo.com. Abstract. The present study was aimed at evaluating the ameliorating effects of Moringa oleifera extract compared to ... At the end of the exposure, 0.2ml of blood samples obtained from individual rat in each group were suspended in ...

  18. Ameliorative effect of ethanolic extract of leaves of Momordica ...

    African Journals Online (AJOL)

    Mormodica charantia has been shown to possess antioxidant, hepatoprotective and anticancer effects while the kidneys have been shown to be the second largest repository of lead in lead poisoining. This study assessed the ameliorative effect of ethanolic leaf extract of Momordica charantia on lead nitrate induced kidney ...

  19. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  20. Designing urban parks that ameliorate the effects of climate change

    NARCIS (Netherlands)

    Brown, R.D.; Vanos, J.; Kenny, N.; Lenzholzer, S.

    2015-01-01

    Many inhabitants of cities throughout the world suffer from health problems and discomfort that are caused by overheating of urban areas, and there is compelling evidence that these problems will be exacerbated by global climate change. Most cities are not designed to ameliorate these effects

  1. Bacterial mediated amelioration of drought stress in drought tolerant ...

    African Journals Online (AJOL)

    Bacterial mediated amelioration of drought stress in drought tolerant and susceptible cultivars of rice (Oryza sativa L.) YS Gusain, US Singh, AK Sharma. Abstract. In the present study, plant growth promoting rhizobacterial (PGPR) strains Pseudomonas fluorescence strain P2, Pseudomonas jessenii R62, Pseudomonas ...

  2. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in ...

    African Journals Online (AJOL)

    Md. Sultan Ahmad

    2015-06-10

    Jun 10, 2015 ... ORIGINAL ARTICLE. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in vitro studies against. Aflatoxin B1 toxicity. Md. Sultan Ahmad *, Sultana Bano, Shafaat Anwar. Department of Zoology, Shibli National (P.G) College, Azamgarh, U.P. 276001, India. Received 17 April 2015; accepted 14 ...

  3. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  4. Salvianolic Acid B Ameliorates Motor Dysfuntion in Spinal Cord ...

    African Journals Online (AJOL)

    Salvianolic Acid B Ameliorates Motor Dysfuntion in Spinal. Cord Injury Rats. Chong Xun, Shouyu Wang, Guang Chen, Yang Hu, Jiaqi Xie and Decheng Lv*. Department of ... Purpose: To evaluate the effect of salvianolic acid B (Sal B) treatment on the motor function of spinal ... China. All the animals were housed at 25 °C in.

  5. Dose-Dependent Amelioration of Gentamicin-Induced ...

    African Journals Online (AJOL)

    increase in serum urea and creatine while 3ml/kg of the same drug completely prevented the increase in serum urea and creatine in this model. Conclusion: Vitamin B-complex dose-dependently ameliorated gentamicin-induced nephrotoxicity in adult Swiss albino rats when given intramuscularly. This finding may have ...

  6. The Effect of Vitamin E on Ameliorating Primary Dysmenorrhea: A ...

    African Journals Online (AJOL)

    Dysmenorrhea or painful menstruation is one of the most common problems of women. Using systematic review and meta‑analysis, this study aimed to determine the effect of vitamin E on ameliorating the intensity of pain of primary dysmenorrhea. Available databases comprising PubMed, Google Scholar, ISI, Science ...

  7. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and changes in osmotic fragility, deformability ...

  8. Ameliorative effects of salt resistance on physiological parameters in ...

    African Journals Online (AJOL)

    Ameliorative effects of salt resistance on physiological parameters in the halophyte Salicornia bigelovii torr. with plant growth-promoting rhizobacteria. Edgar Omar Rueda-Puente, R Prabhaharan, B Murillo-Amador, F Ruiz-Espinoza, M Puente, RD Valdez-Cepeda ...

  9. Ameliorative effect of the hydroethanolic whole plant extract of ...

    African Journals Online (AJOL)

    At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined. Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), ...

  10. Erratum: Unripe Musa paradisiaca Fruit Diet Ameliorates Impaired ...

    African Journals Online (AJOL)

    In the article “Unripe Musa paradisiaca Fruit Diet Ameliorates Impaired Glucose Regulation Caused by Iron-Induced Oxidative Stress” by Ige A.O, Oyekunle A.O, Olaoye M. O and Adewoye E.O which appeared on pages 301-308 of the September 2017 issue, it has been observed that the name of the second author was ...

  11. Using innovation platforms to scale out soil acidity- ameliorating ...

    African Journals Online (AJOL)

    Dr V.Kabambe

    2012-01-10

    Jan 10, 2012 ... ameliorating technologies in Dedza district in central. Malawi. V. H. Kabambe1* ... end of the project support in 2008, the participating farmers were willing to invest in the technology and raised funds for purchase ..... Engineering Commodity Group Project Meeting held at Mzuzu Hotel,. 10-15 August 1996.

  12. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... Accepted 28 April, 2008. This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and ...

  13. The ameliorative effects of Moringa oleifera leaf extract on ...

    African Journals Online (AJOL)

    The present study was aimed at evaluating the ameliorating effects of Moringa oleifera extract compared to captopril and candesartan cilexetil on cardiovascular functions and osmotic fragility of rats exposed to petrol vapour. Twenty five adult male Wistar rats (130g-200g) were randomly grouped to five with five rats in a ...

  14. Viabilidade espermática e geração de metabólicos reativos do oxigênio(ROS) no sêmen ovino criopreservado em diluidor aditivado de lauril de sódio (OE), trolox-C e catalase

    OpenAIRE

    Maia, Marciane da Silva [UNESP

    2006-01-01

    O Objetivo deste estudo foi determinar o efeito da adição do surfactante lauril sulfato de sódio (Orvus es Paste OEP) e dos antioxidantes Trolox-C (6- hidroxi-2, 5,7,8-tetrametilcroman-2-acido carboxílico) e catalase ao meio diluidor, na motilidade espermática, integridade de membrana plasmática, acrossomal e mitocondrial, estádio de capacitação e geração de radicais livres no espermatozóide ovino pós-descongelação. Para isso, foram realizados dois experimentos. No Experimento 1, avaliou-se o...

  15. Biochar from commercially cultivated seaweed for soil amelioration

    OpenAIRE

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum ? brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma ? red seaweeds). While there is some variability in biochar properties as ...

  16. Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

    Science.gov (United States)

    Jeon, Se Jin; Kim, Boseong; Ryu, Byeol; Kim, Eunji; Lee, Sunhee; Jang, Dae Sik; Ryu, Jong Hoon

    2017-01-01

    To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems. PMID:27829270

  17. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum – brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma – red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity. PMID:25856799

  18. Administration of red ginseng ameliorates memory decline in aged mice.

    Science.gov (United States)

    Lee, Yeonju; Oh, Seikwan

    2015-07-01

    It has been known that ginseng can be applied as a potential nutraceutical for memory impairment; however, experiments with animals of old age are few. To determine the memory enhancing effect of red ginseng, C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12% red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4 mo and 21 mo old, respectively) were used as the control group. The effect of red ginseng, which ameliorated memory impairment in aged mice, was quantified using Y-maze test, novel objective test, and Morris water maze. Red ginseng ameliorated age-related declines in learning and memory in older mice. In addition, red ginseng's effect on the induction of inducible nitric oxide synthase and proinflammatory cytokines was investigated in the hippocampus of aged mice. Red ginseng treatment suppressed the production of age-processed inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-1β expressions. Moreover, it was observed that red ginseng had an antioxidative effect on aged mice. The suppressed glutathione level in aged mice was restored with red ginseng treatment. The antioxidative-related enzymes Nrf2 and HO-1 were increased with red ginseng treatment. The results revealed that when red ginseng is administered over long periods, age-related decline of learning and memory is ameliorated through anti-inflammatory activity.

  19. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  20. Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

    2017-12-01

    This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

  1. Biochar from commercially cultivated seaweed for soil amelioration.

    Science.gov (United States)

    Roberts, David A; Paul, Nicholas A; Dworjanyn, Symon A; Bird, Michael I; de Nys, Rocky

    2015-04-09

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum--brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma--red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  2. A note on inventory model for ameliorating items with time dependent second order demand rate

    Directory of Open Access Journals (Sweden)

    Gobinda Chandra Panda

    2013-03-01

    Full Text Available Background: This paper is concerned with the development of ameliorating inventory models. The ameliorating inventory is the inventory of goods whose utility increases over the time by ameliorating activation. Material and Methods: This study is performed according to two areas: one is an economic order quantity (EOQ model for the items whose utility is ameliorating in accordance with Weibull distribution, and the other is a partial selling quantity (PSQ model developed for selling the surplus inventory accumulated by ameliorating activation with linear demand. The aim of this paper was to develop a mathematical model for inventory type concerned in the paper. Numerical examples were presented show the effect of ameliorating rate on inventory polices.  Results and Conclusions:  The inventory model for items with Weibull ameliorating is developed. For the case of small ameliorating rate (less than linear demand rate, EOQ model is developed, and for the case where ameliorating rate is greater than linear demand rate, PSQ model is developed.  .  

  3. Incremental Beliefs About Ability Ameliorate Self-Doubt Effects

    Directory of Open Access Journals (Sweden)

    Qin Zhao

    2015-12-01

    Full Text Available Past research has typically shown negative effects of self-doubt on performance and psychological well-being. We suggest that these self-doubt effects largely may be due to an underlying assumption that ability is innate and fixed. The present research investigated the main hypothesis that incremental beliefs about ability might ameliorate negative effects of self-doubt. We examined our hypotheses using two lab tasks: verbal reasoning and anagram tasks. Participants’ self-doubt was measured and beliefs about ability were measured after participants read articles advocating either for incremental or entity theories of ability. American College Testing (ACT scores were obtained to index actual ability level. Consistent with our hypothesis, for participants who believed ability was relatively fixed, higher self-doubt was associated with increased negative affect and lower task performance and engagement. In contrast, for participants who believed that ability was malleable, negative self-doubt effects were ameliorated; self-doubt was even associated with better task performance. These effects were further moderated by participants’ academic ability. These findings suggest that mind-sets about ability moderate self-doubt effects. Self-doubt may have negative effects only when it is interpreted as signaling that ability is immutably low.

  4. Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

    Science.gov (United States)

    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2014-01-17

    Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. © 2013.

  5. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  6. Phytoceramide shows neuroprotection and ameliorates scopolamine-induced memory impairment.

    Science.gov (United States)

    Jung, Jae-Chul; Lee, Yeonju; Moon, Sohyeon; Ryu, Jong Hoon; Oh, Seikwan

    2011-10-28

    The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease.

  7. Arginase Inhibition Ameliorates Hepatic Metabolic Abnormalities in Obese Mice

    Science.gov (United States)

    Moon, Jiyoung; Do, Hyun Ju; Cho, Yoonsu; Shin, Min-Jeong

    2014-01-01

    Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function. PMID:25057910

  8. Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice.

    Science.gov (United States)

    Choi, Seung Hee; Leem, Jaechan; Park, Sungmi; Lee, Chong-Kee; Park, Keun-Gyu; Lee, In-Kyu

    2017-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.

  9. Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

    Science.gov (United States)

    Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D.; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J.; Orban, Csaba; Passetti, Filippo; Paterson, Louise M.; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M.; Bullmore, Edward T.; Lingford‐Hughes, Anne R.; Deakin, Bill; Nutt, David J.; Sahakian, Barbara J.; Robbins, Trevor W.; Voon, Valerie

    2017-01-01

    Abstract Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50‐mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly‐drug‐dependent individuals compared with 36 healthy volunteers. Graph theoretic and network‐based statistical analysis of resting‐state functional magnetic resonance imaging (MRI) data revealed that alcohol‐dependent subjects had reduced functional connectivity of a dispersed network compared with both poly‐drug‐dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol‐dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly‐substance‐dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology. PMID:28247526

  10. 75 FR 58415 - Prospective Grant of Exclusive License: Prevention, Prophylaxis, Cure, Amelioration, and/or...

    Science.gov (United States)

    2010-09-24

    ... Exclusive License: Prevention, Prophylaxis, Cure, Amelioration, and/or Treatment of Infection and/or the... dengue virus, characterized by rash, high fever, and severe, sometimes persistent arthritis. The field of use may be limited to ``Prevention, prophylaxis, cure, amelioration, and/or treatment of infection and...

  11. Mitigation of NADH: ubiquinone oxidoreductase deficiency by chronic Trolox treatment.

    NARCIS (Netherlands)

    Koopman, W.J.H.; Verkaart, S.A.J.; Emst-de Vries, S.E. van; Grefte, S.; Smeitink, J.A.M.; Nijtmans, L.G.J.; Willems, P.H.G.M.

    2008-01-01

    Deficiency of mitochondrial NADH:ubiquinone oxidoreductase (complex I), is associated with a variety of clinical phenotypes such as Leigh syndrome, encephalomyopathy and cardiomyopathy. Circumstantial evidence suggests that increased reactive oxygen species (ROS) levels contribute to the

  12. Quercetin Treatment Ameliorates Systemic Oxidative Stress in Cirrhotic Rats

    Science.gov (United States)

    Vieira, Emanuelle Kerber; Bona, Silvia; Di Naso, Fábio Cangeri; Porawski, Marilene; Tieppo, Juliana; Marroni, Norma Possa

    2011-01-01

    Our aim was to investigate whether the antioxidant quercetin protects against liver injury and ameliorates the systemic oxidative stress in rats with common bile duct ligation. Secondary biliary cirrhosis was induced through 28 days of bile duct obstruction. Animals received quercetin (Q) after 14 days of obstruction. Groups of control (CO) and cirrhotic (CBDL) animals received a daily 50 mg/kg body weight i.p. injection of quercetin (CO + Q; CBDL + Q) or vehicle (CO; CBDL). Quercetin corrected the reduction in superoxide dismutase (SOD), catalase CAT, and glutathione peroxidase GPx activities and prevented the increase of thiobarbituric acid reactive substances (TBARS), aminotransferases, and alkaline phosphatase in cirrhotic animals. Quercetin administration also corrected the reduced total nitrate concentration in the liver and prevented liver fibrosis and necrosis. These effects suggest that quercetin might be a useful agent to preserve liver function and prevent systemic oxidative stress. PMID:21991520

  13. Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Junya Kawai

    2014-01-01

    Full Text Available Pleurotus eryngii (P. eryngii is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI. Intranasal instillation of lipopolysaccharide (LPS (10 μg/site/mouse induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

  14. Ameliorating the effects of global crisis on human resources

    Directory of Open Access Journals (Sweden)

    Wilfred UKPERE

    2011-06-01

    Full Text Available Capitalist globalisation has produced certain negative consequences for human resources, industrial democracy and humanity in general. Globalisation is a powerful force that cannot be denied, however, conversely, it has also threatened life, in a broader sense. Globalisation was perceived by globalisers as a worldwide remedy for worldwide problems, but is viewed with great pessimism amongst proletariat (workers. In fact, current globalisation has an enormous negative impact on human resources, industrial democracy and humanity, at large. Hence, the aim of this paper is to proffer mechanisms, which can ameliorate negative impacts of globalisation on human resources, industrial democracy and humanity. It is the author’s belief that if current postulates are considered, globalisation might present a different picture, which could have positive effects on human resources, industrial democracy and humanity, in general.

  15. Biochar Ameliorate Drought and Salt Stress in Plants

    DEFF Research Database (Denmark)

    Saleem Akhtar, Saqib

    . Drought and salinity are the two most crucial abiotic stresses that limit crops production worldwide. In this PhD project, it was hypothesized that biochar could be used to effectively mitigate drought and salinity stresses in crop plants due to its putative physiochemical properties. The overall...... objectives of the present PhD project were to reveal the mechanisms by which biochar addition mitigates negative effect of drought and salinity stress on plants and to test the efficacy of biochar when applied in combination with already existing drought (like DI and PRD) and salt management (inoculation...... of plant with halophytic plant growth promoting bacteria) approaches. The results showed that: - Biochar mitigated drought stress in plants by enhancing soil moisture availability due to its high porosity and large surface area - Biochar ameliorated salinity stress in plant by a high transient Na+ binding...

  16. Flemingia macrophylla Extract Ameliorates Experimental Osteoporosis in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Hui-Ya Ho

    2011-01-01

    Full Text Available Flemingia macrophylla (Leguminosae, a native plant of Taiwan, is used as folk medicine. An in vitro study showed that a 75% ethanolic extract of F. macrophylla (FME inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A, was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME.

  17. Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.

    Science.gov (United States)

    Liu, Ting Ting; Zeng, Yi; Tang, Kun; Chen, XueMeng; Zhang, Wei; Xu, Xiao Le

    2017-07-01

    Dihydromyricetin, the most abundant flavonoid in Ampelopsis grossedentata, exerts numerous pharmacological activities, including anti-inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities; however, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of dihydromyricetin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr -/- ) mice. Blood samples were collected for determination of serum lipid profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology, hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation were performed on liver and aorta samples by molecular biology methods. The effects of dihydromyricetin on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation were further studied. (1) Dihydromyricetin ameliorated hyperlipidemia, reduced serum ox-LDL, IL-6 and TNF-α levels in HFD-fed LDLr -/- mice. Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and increased protein expressions of PPARα, LXRα and ABCA1. (3) It inhibited atherosclerotic lesion formation and favoured features of plaque stability. (4) Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the reduced IL-6 and TNF-α mRNA expression; (5) it prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in the liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation and enhanced cholesterol efflux. These findings suggest that dihydromyricetin could reduce atherosclerosis via its pleiotropic effects, including improvement of endothelial dysfunction, inhibition of macrophage foam cell formation

  18. Elm bark extract improves immunomodulation and ameliorates oxidative stress in irradiated mice

    Directory of Open Access Journals (Sweden)

    You-Suk Lee

    2017-03-01

    Conclusion: Our results indicate that EB extract (50 mg/kg body weight protects against radiation damage, at least in part, by improving immunomodulation and ameliorating oxidative stress in irradiated mice.

  19. Nitric oxide synthase inhibition ameliorates nicotine-induced sperm function decline in male rats

    Directory of Open Access Journals (Sweden)

    Ibukun P. Oyeyipo

    2015-09-01

    Conclusion: Taken together, the present data indicate the abilities of l-NAME to ameliorate nicotine-induced spermatotoxic effects in male rats via a mechanism dependent on the circulating testosterone level.

  20. Ameliorative Effect of Allopurinol on Vascular Complications of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hany M. El-Bassossy

    2015-01-01

    Full Text Available The aim of the current study was to evaluate the possible protective effect of allopurinol (Allo on experimentally induced insulin resistance (IR and vascular complications. Rats were divided into four groups: control, IR, allopurinol-treated IR (IR-Allo, and allopurinol-treated control (Allo. IR was induced by adding fructose and high fat, high salt diet for 12 weeks. The results showed that Allo has alleviated the increased level of TNF-α and the systolic, diastolic, mean, and notch pressure observed in IR with no change in pulse pressure. In addition, Allo decreased the heart rate in the treated group compared to IR rats. On the other hand, it has no effect on increased levels of insulin, glucose, fructosamine, or body weight gain compared to IR group, while it increased significantly the insulin level and body weight without hyperglycemia in the control group. Moreover, Allo treatment ameliorated increased level of 4HNE, Ang II, and Ang R1. In conclusion, the results of the current study show that Allo has a protective effect on vascular complications of IR which may be attributed to the effect of Allo on decreasing the TNF-α, 4HNE, Ang II, and Ang R1 as well as increasing the level of insulin secretion.

  1. Insulin sensitizer prevents and ameliorates experimental type 1 diabetes.

    Science.gov (United States)

    Valitsky, Michael; Hoffman, Amnon; Unterman, Terry; Bar-Tana, Jacob

    2017-12-01

    Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthyl-substituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D. Copyright © 2017 the American Physiological Society.

  2. use of tolerant plants for environmental amelioration of saline soils

    International Nuclear Information System (INIS)

    Salem, S.M.

    2007-01-01

    the objectives of this work are to use halophyte plants as suitable means for ameliorating salt-affected soils and to evaluate the use of saline water in irrigation halophyte plants as well as to determine the impact of saline irrigation on different properties of the salt -affected soil. two halophyte plants (i.e Atriplex nummularia and leptochloa fusca ( kallar grass)) were grown for 120 days during growth seasons of 2004 (first season) and 2005 ( second season)in lysimeters of 250 k gs capacity, which were filled with 180 k gs soil. the experiment was a randomized complete block factorial, involving two factors. the first factor was halophyte type (two halophytes were used, kallar grass and atriplex).the investigated data point to Ca accumulation in soil profile was increased with the increase in salinity level of irrigation water. increasing salinity of irrigation water sharply increased Mg accumulation in soil profile, especially with the cultivation of atriplex, where Mg accumulation by kallar grass was dramatically more than those occurred by atriplex.. kallar grass appears to have a good ability to reduce R Na C from the three soil layers under different saline irrigation waters rather than atriplex. R Na C (under using fresh water) was the lowest in the three soil layers rather the rest of the saline irrigation waters in both case of the two plants. a high residual sodium concentration recorded in soil cultivated by atriplex rather than kallar grass

  3. Coniferyl Aldehyde Ameliorates Radiation Intestine Injury via Endothelial Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ye Ji; Jung, Myung Gu; Lee, Yoonjin; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yunsil [Ewha Woman' s Univ., Seoul (Korea, Republic of); Ko, Younggyu [Korea Univ., Seoul (Korea, Republic of)

    2014-05-15

    Cancer treatments related gastrointestinal toxicity has also been recognized as a significant economic burden. Especially, extensive apoptosis of microvascular endothelial cell of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Coniferyl aldehyde (CA) is phenolic compounds isolated from cork stoppers, and one of the major pyrolysis products of lignin. Shi H. was support for the empirical use of CA as a medicinal food for cardiovascular diseases. CA has positive effect in broad way but there is no consequence in radiation induced intestine damage. Here, we investigate effect of CA on small intestine after abdominal IR to mice in this study. In this study, CA increased the survival rate in C3H mice against 13.5 Gy abdominal IR. We found CA protects small intestine via preventing endothelial cell apoptosis and enhancing their angiogenic activity. CA also showed protective effect on crypt cell survival. Endothelial cell survival may affect crypt cell protection against IR. From this data, we concluded that CA is effective for protection against abdominal radiation injury. CA could ameliorate side-effect of radiation therapy.

  4. Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Xuan Du

    2018-01-01

    Full Text Available Background. To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods. 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups. Adipose distribution was quantified with computerized tomography according to anatomy, dividing into visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT, adding up to total adipose tissue (TAT. Results. The 6-month exenatide treatment dramatically ameliorated the glucose and lipid profile, improved insulin sensitivity, and mainly decreased VAT and also the ratio of VAT/SAT (RVS. The following 6-month glargine treatment increased VAT. The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters. Conclusion. Exenatide is an ideal treatment for obese type 2 diabetic patients in the aspect of adipose tissue distribution. Sequential treatment of exenatide and glargine could be an alternative for low-income patients who cannot afford GLP-1 agonist for long time. This trial is registered with ChiCTR-OOC-17013679.

  5. Levetiracetam ameliorates ovarian function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Akman, Levent; Erbas, Oytun; Akdemir, Ali; Yavasoglu, Altug; Taskiran, Dilek; Kazandi, Mert

    2015-01-01

    Diabetes mellitus can adversely affect gonadal function. In the present study, we aimed to investigate the protective effects and mechanism of action of levetiracetam (LEV) on the ovaries in a streptozotocin (STZ)-induced diabetes model in rats. Twenty-one adult female rats were assigned to three groups as control, diabetes group treated with 1 mL/kg/d saline (STZ + SP) and diabetes group treated with 600 mg/kg/d LEV (STZ + LEV). Following 4 weeks treatment, blood samples were collected for biochemical analysis and ovariectomy was performed for histopathological examination. Plasma anti-Mullerian hormone (AMH), glutathione and total anti-oxidant capacity values were significantly lower whereas lipid peroxides and transforming growth factor-β (TGF-β) values were significantly higher in STZ + SP group compared to control. LEV treatment successfully decreased lipid peroxidation and TGF-β levels, and also increased anti-oxidant parameters and AMH levels in diabetic rats. Saline-treated rats significantly displayed ovarian degeneration and decreased counts of follicles. However, treatment of diabetic rats with LEV effectively prevented the degenerative changes and follicle loss. Also, LEV suppressed ovarian nuclear factor-kappa B (NF-kB) immunoexpression in diabetic rats. Taken together, we propose that LEV can ameliorate the adverse effects of diabetes on ovarian function via decreasing NF-kB expression and oxidative stress and increasing anti-oxidant status in rats.

  6. Cannabidiol treatment ameliorates ischemia/reperfusion renal injury in rats.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2012-09-17

    To investigate the protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, against renal ischemia/reperfusion injury in rats. Bilateral renal ischemia was induced for 30 min followed by reperfusion for 24h. Cannabidiol (5mg/kg, i.v.) was given 1h before and 12h following the procedure. Ischemia/reperfusion caused significant elevations of serum creatinine and renal malondialdehyde and nitric oxide levels, associated with a significant decrease in renal reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters induced by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced kidney damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in ischemic/reperfused kidney tissue. Cannabidiol, via its antioxidant and anti-inflammatory properties, may represent a potential therapeutic option to protect against ischemia/reperfusion renal injury. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Listening to classical music ameliorates unilateral neglect after stroke.

    Science.gov (United States)

    Tsai, Pei-Luen; Chen, Mei-Ching; Huang, Yu-Ting; Lin, Keh-Chung; Chen, Kuan-Lin; Hsu, Yung-Wen

    2013-01-01

    OBJECTIVE. We determined whether listening to excerpts of classical music ameliorates unilateral neglect (UN) in stroke patients. METHOD. In this within-subject study, we recruited and separately tested 16 UN patients with a right-hemisphere stroke under three conditions within 1 wk. In each condition, participants were asked to complete three subtests of the Behavioral Inattention Test while listening to classical music, white noise, or nothing. All conditions and the presentation of the tests were counterbalanced across participants. Visual analog scales were used to provide self-reported ratings of arousal and mood. RESULTS. Participants generally had the highest scores under the classical music condition and the lowest scores under the silence condition. In addition, most participants rated their arousal as highest after listening to classical music. CONCLUSION. Listening to classical music may improve visual attention in stroke patients with UN. Future research with larger study populations is necessary to validate these findings. Copyright © 2013 by the American Occupational Therapy Association, Inc.

  8. Cellulose Supplementation Early in Life Ameliorates Colitis in Adult Mice

    Science.gov (United States)

    Nagy-Szakal, Dorottya; Hollister, Emily B.; Luna, Ruth Ann; Szigeti, Reka; Tatevian, Nina; Smith, C. Wayne; Versalovic, James; Kellermayer, Richard

    2013-01-01

    Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC]) where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS) colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001]), and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]). Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation. PMID:23437211

  9. Yangjing Capsule Ameliorates Spermatogenesis in Male Mice Exposed to Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Hongle Zhao

    2015-01-01

    Full Text Available Yangjing capsule (YC, a traditional Chinese compound herbal preparation, has been proven as an effective drug to improve spermatogenesis in clinical practice. However, its pharmacological mechanisms were not fully clarified. This study was designed to investigate the protective effects of YC on spermatogenesis in the mouse model of spermatogenesis dysfunction induced by cyclophosphamide (CP. The administration of YC significantly increased the epididymal index, sperm count, and sperm motility of model mice. Histopathological changes demonstrated that CP caused obvious structural damage to testis, which were reversed by the administration of YC. Results from TUNEL assay showed that treatment with YC dramatically decreased the apoptosis of spermatogenic cell induced by CP. Moreover, YC treatment could inhibit the mRNA and protein expression of Bax to Bcl-2 and also raised expression of AR at both mRNA and protein levels. These data suggest that YC might ameliorate spermatogenesis in male mice exposed to CP through inhibiting the apoptosis of spermatogenic cell and enhancing the actions of testosterone in spermatogenesis.

  10. Stopping the error cascade: a report on ameliorators from the ASIPS collaborative

    Science.gov (United States)

    Parnes, Bennett; Fernald, Douglas; Quintela, Javán; Araya‐Guerra, Rodrigo; Westfall, John; Harris, Daniel; Pace, Wilson

    2007-01-01

    Objective To present a novel examination of how error cascades are stopped (ameliorated) before they affect patients. Design Qualitative analysis of reported errors in primary care. Setting Over a three‐year period, clinicians and staff in two practice‐based research networks voluntarily reported medical errors to a primary care patient safety reporting system, Applied Strategies for Improving Patient Safety (ASIPS). The authors found a number of reports where the error was corrected before it had an adverse impact on the patient. Results Of 754 codeable reported events, 60 were classified as ameliorated events. In these events, a participant stopped the progression of the event before it reached or affected the patient. Ameliorators included doctors, nurses, pharmacists, diagnostic laboratories and office staff. Additionally, patients or family members may be ameliorators by recognising the error and taking action. Ameliorating an event after an initial error requires an opportunity to catch the error by systems, chance or attentiveness. Correcting the error before it affects the patient requires action either directed by protocols and systems or by vigilance, power to change course and perseverance on the part of the ameliorator. Conclusion Despite numerous individual and systematic methods to prevent errors, a system to prevent all potential errors is not feasible. However, a more pervasive culture of safety that builds on simple acts in addition to more costly and complex electronic systems may improve patient outcomes. Medical staff and patients who are encouraged to be vigilant, ask questions and seek solutions may correct otherwise inevitable wrongs. PMID:17301195

  11. Amelioration and reforestation of sulfurous mine soils in Lusatia (eastern Germany)

    International Nuclear Information System (INIS)

    Katzur, J.; Haubold-Rosar, M.

    1996-01-01

    In Germany nearly 1.550 km 2 have been claimed by brown coal mining until now. Mine soils formed of carboniferous and sulfurous overburden are classified as sulfurous mine soils. They remain vegetation-free for decades and may be cultivated only after soil amelioration. The objective of amelioration is a sustained improvement of soil reaction. Lime requirement for the achievement of a certain pH-value is calculated from acid-base-balance (SBB). Lime fertilizers and base-rich brown coal ashes are used for amelioration. As ashes have several advantages, their application is recommended. The ameliorative application of lime fertilizer or brown coal ash should be incorporated intensively into the soil to a depth of 60 cm, better 100 cm. Amelioration includes a mineral fertilization with N, P and K. Afforestation with Pinus sylvestris, Pinus nigra, Larix decidua, Larix eurolepis. Tilia cordata, Quercus rubra and Quercus petraea on ameliorated mine soils show surprising good results. Multi-species stands have very positive effects on soil formation. Raw humus is formed under pine and larch, and under deciduous trees moder and mull with higher bioactivity and better development of water and nutrient balance in the topsoil are found. 55 refs., 6 figs., 4 tabs

  12. Carvacrol Ameliorates Ligation-Induced Periodontitis in Rats.

    Science.gov (United States)

    Kuo, Po-Jan; Hung, Tsung-Fu; Lin, Chi-Yu; Hsiao, Hsiang-Yin; Fu, Min-Wen; Hong, Po-Da; Chiu, Hsien-Chung; Fu, Earl

    2017-07-01

    This study aims to evaluate the ameliorative effect of carvacrol, an anti-inflammatory monoterpenoid phenol and a major component of Plectranthus amboinicus, on periodontal damage in an experimental rat model of periodontitis. Forty Sprague-Dawley rats were divided into ligation (Lig), non-ligation (n-Lig), and two ligation plus carvacrol (Lig+C) groups. Carvacrol (17.5 or 35.0 mg/kg body weight/day) was administered intragastrically from 1 day before ligation. On day 8, dental alveolar bone loss and gingival inflammation in periodontal specimens were examined by dental radiography, microcomputed tomography, and histology. Expressions of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase messenger (m)RNAs, and levels of matrix metalloproteinase (MMP)-2 and MMP-9 in gingiva were examined by reverse transcription-polymerase chain reaction and zymography. Dental radiography revealed periodontal bone-supporting ratios in Lig and Lig+C groups were lower than the n-Lig group, with Lig group ratios being lowest. Compared with the n-Lig group, the cemento-enamel junction-bone distance was significantly longer in Lig and Lig+C groups, with Lig+C groups showing shorter distances regardless of radiographic methods used. Histology and histometry showed less inflammatory area and stronger connective tissue attachment in Lig+C groups than in the Lig group. Cytokine/mediator mRNA expression and MMP-9 levels were reduced in the Lig+C groups. Carvacrol reduced tissue damage and bone loss caused by ligation-induced periodontitis. The present results indicate that carvacrol might reduce tissue destruction by downregulating expression of proinflammatory mediators and MMP-9.

  13. Orthosiphon stamineus (Misai Kucing) ameliorated postmenopausal osteoporosis in rat model.

    Science.gov (United States)

    Bokhari, Rubiatul Adawiyah; Lau, Seng Fong; Mohamed, Suhaila

    2018-02-01

    Orthosiphon stamineus (OS) or Misai Kucing (Java tea) is a popular herbal supplement from Southeast Asia for various metabolic, age-related diseases. This study investigated the potential use of OS leaf extracts to ameliorate osteoporosis in ovariectomized rats. Fifty-six female Sprague-Dawley rats were randomly allocated into eight groups (n = 7): SHAM (healthy sham control); OVX (ovarietomized) nontreated rats (negative control); OVX + Remifemin (100 mg/kg body weight), and 2% green tea extract (positive controls); OVX + OS 50% ethanolic and aqueous extracts, both at either 150 or 300 mg/kg. After 16 weeks, the rats' bones and blood were evaluated for osteoporosis indicators (protein and mRNA expressions), micro-computed tomography for bone histomorphometry, and three-point bending test for tibia mechanical strength. The extracts dose-dependently and significantly (P < 0.05) improved bone strength and flexibility, bone mineral density, bone formation protein markers (P1NP), and bone histomorphometry. All extracts reduced the inflammation biomarker (interleukin-6). The extracts up-regulated osteoblastogenesis (bone morphogenetic protein-2) and collagen-1 synthesis (collagen type 1 alpha-1) mRNA expressions, and down-regulated bone resorption (TNFSF11 and nuclear factor-kappa B) mRNA expressions. Both the water and 50% ethanolic extract were effective. The effective dose is equivalent to 25 to 50 mg/kg extract for humans. The extract showed bone-protective and antiosteoporotic effects (improving bone strength, flexibility, bone density, and bone morphometry) by reducing inflammation and the bone resorption biomarkers, while enhancing bone formation biomarkers and collagen synthesis.

  14. Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis.

    Science.gov (United States)

    Yu, Hong-Jing; Liu, Wei; Chang, Zhen; Shen, Hui; He, Li-Juan; Wang, Sha-Sha; Liu, Lu; Jiang, Yuan-Ying; Xu, Guo-Tong; An, Mao-Mao; Zhang, Jun-Dong

    2015-06-07

    To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1β, IL-10, IL-6, G-CSF and MIP-2 (P pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-κB and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-κB subunit p65 and in the phosphorylation of IκB-α, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-α, G-CSF and GM-CSF (P pylori in the stomach was also significantly reduced following BIFICO treatment (P pylori-induced gastritis by inhibiting the inflammatory response in gastric epithelial cells.

  15. Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.

    Science.gov (United States)

    Slattery, Patrick; Frölich, Stefanie; Goren, Itamar; Nüsing, Rolf M

    2017-06-01

    Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2 -/- mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg·g -1 ·day -1 ) for the first 10 days after birth ameliorated impaired kidney development in COX-2 -/- pups resulting in an increase in glomerular size and fewer immature superficial glomeruli. However, impaired renal subcortical growth was not corrected. Increasing renal tubular flow by volume load or injections of KCl did not relieve the renal histomorphological damage. Administration of torsemide and spironolactone also affected nephrogenesis resulting in diminished glomeruli and cortical thinning. Treatment of COX-2 -/- pups with NaCl/DOCA caused a stronger mitigation of glomerular size and induced a slight but significant growth of cortical tissue mass. After birth, renal mRNA expression of NHE3, NKCC2, ROMK, NCCT, ENaC, and Na + /K + -ATPase increased relative to postnatal day 2 in wild-type mice. However, in COX-2 -/- mice, a significantly lower expression was observed for NCCT, whereas NaCl/DOCA treatment significantly increased NHE3 and ROMK expression. Long-term effects of postnatal NaCl/DOCA injections indicate improved kidney function with normalization of pathologically enhanced creatinine and urea plasma levels; also, albumin excretion was observed. In summary, we present evidence that salt supplementation during the COX-2-dependent time frame of nephrogenesis partly reverses renal morphological defects in COX-2 -/- mice and improves kidney function. Copyright © 2017 the American Physiological Society.

  16. NAD+ biosynthesis ameliorates a zebrafish model of muscular dystrophy.

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    Michelle F Goody

    Full Text Available Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction

  17. Aedes aegypti salivary gland extract ameliorates experimental inflammatory bowel disease.

    Science.gov (United States)

    Sales-Campos, Helioswilton; de Souza, Patricia Reis; Basso, Paulo José; Ramos, Anderson Daniel; Nardini, Viviani; Chica, Javier Emílio Lazo; Capurro, Margareth Lara; Sá-Nunes, Anderson; de Barros Cardoso, Cristina Ribeiro

    2015-05-01

    Current therapies for inflammatory bowel disease (IBD) are not totally effective, resulting in persistent and recurrent disease for many patients. Mosquito saliva contains immunomodulatory molecules and therein could represent a novel therapy for IBD. Here, we demonstrated the therapeutic activity of salivary gland extract (SGE) of Aedes aegypti on dextran sulfate sodium (DSS)-induced colitis. For this purpose, C57BL/6 male mice were exposed to 3% DSS in drinking water and treated with SGE at early (days 3-5) or late (days 5-8) time points, followed by euthanasia on days 6 and 9, respectively, for sample collection. The results showed an improvement in clinical disease outcome and postmortem scores after SGE treatment, accompanied by the systemic reduction in peripheral blood lymphocytes, with no impact on bone marrow and mesenteric lymph nodes cellularity or macrophages toxicity. Moreover, a local diminishment of IFN-γ, TNF-α, IL-1β and IL-5 cytokines together with a reduction in the inflammatory area were observed in the colon of SGE-treated mice. Strikingly, early treatment with SGE led to mice protection from a late DSS re-challenging, as observed by decreased clinical and postmortem scores, besides reduced circulating lymphocytes, indicating that the mosquito saliva may present components able to prevent disease relapse. Indeed, high performance liquid chromatography (HPLC) experiments pointed to a major SGE pool fraction (F3) able to ameliorate disease signs. In conclusion, SGE and its components might represent a source of important immunomodulatory molecules with promising therapeutic activity for IBD. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Economic recession and suicidal behaviour: Possible mechanisms and ameliorating factors.

    Science.gov (United States)

    Haw, Camilla; Hawton, Keith; Gunnell, David; Platt, Stephen

    2015-02-01

    A growing body of research evidence from countries around the world indicates that economic recession is associated with increases in suicide, particularly in males of working age. To explore contributory and ameliorating factors associated with economic recession and suicide and thereby stimulate further research in this area and encourage policy makers to consider how best to reduce the impact of recession on mental health and suicidal behaviour. We conducted a selective review of the worldwide literature focusing on possible risk factors, mechanisms and preventative strategies for suicidal behaviour linked to economic recession. A model of how recession might affect suicide rates is presented. A major and often prolonged effect of recession is on unemployment and job insecurity. Other important effects include those exerted by financial loss, bankruptcy and home repossession. It is proposed these factors may lead directly or indirectly to mental health problems such as depression, anxiety and binge drinking and then to suicidal behaviour. Countries with active labour market programmes and sustained welfare spending during recessions have less marked increases in suicide rates than those that cut spending on welfare and job-search initiatives for the unemployed. Other measures likely to help include targeted interventions for unemployed people, membership of social organisations and responsible media reporting. Good primary care and mental health services are needed to cope with increased demand in times of economic recession but some governments have in fact reduced healthcare spending as an austerity measure. The research evidence linking recession, unemployment and suicide is substantial, but the evidence for the other mechanisms we have investigated is much more tentative. We describe the limitations of the existing body of research as well as make suggestions for future research into the effects of economic recession on suicidal behaviour. © The Author

  19. Caloric restriction ameliorates acrolein-induced neurotoxicity in rats.

    Science.gov (United States)

    Huang, Ying-Juan; Zhang, Li; Shi, Lan-Ying; Wang, Yuan-Yuan; Yang, Yu-Bin; Ke, Bin; Zhang, Ting-Ying; Qin, Jian

    2018-03-01

    Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and oxidative damage induced by acrolein is hypothesized to involve in the etiology of Alzheimer's disease (AD). Calorie restriction (CR) is the only non-genetic intervention that has consistently been verified to retard aging by ameliorating oxidative stress. Therefore, we investigated the effects of CR on acrolein-induced neurotoxicity in Sprague-Dawley (SD) rats. A total of 45 weaned and specific-pathogen-free SD rats (male, weighing 180-220 g) were gavage-fed with acrolein (2.5 mg/kg/day) and fed ab libitum of 10 g/day or 7 g/day (representing 30% CR regimen), or gavage-fed with same volume of tap water and fed al libitum as vehicle control for 12 weeks. After behavioral test conducted by Morris Water Maze, SD rats were sacrificed and brain tissues were prepared for histochemical evaluation and Western blotting to detect alterations in oxidative stress, BDNF/TrkB pathway and key enzymes involved in amyloid precursor protein (APP) metabolism. Treatment with 30% CR in SD rats significantly attenuated acrolein-induced cognitive impairment. Oxidative damage including deletion of glutathione and superoxide dismutase and sharp rise in malondialdehyde were notably improved by 30% CR. Further study suggested that 30% CR showed protective effects against acrolein by modulating BDNF/TrkB signaling pathways. Moreover, 30% CR restored acrolein-induced changes of APP, β-secretase, α-secretase and receptor for advanced glycation end products. These findings suggest that CR may provide a promising approach for the treatment of AD, targeting acrolein. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia.

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    J Pedro Fernández-Murray

    2016-01-01

    Full Text Available Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation. The function of SLC25A38 is not known. Here we report that the SLC25A38 protein, and its yeast homolog Hem25, are mitochondrial glycine transporters required for the initiation of heme synthesis. To do so, we took advantage of the fact that mitochondrial glycine has several roles beyond the synthesis of heme, including the synthesis of folate derivatives through the glycine cleavage system. The data were consistent with Hem25 not being the sole mitochondrial glycine importer, and we identify a second SLC25 family member Ymc1, as a potential secondary mitochondrial glycine importer. Based on these findings, we observed that high levels of exogenous glycine, or 5-aminolevulinic acid (5-Ala a metabolite downstream of Hem25 in heme biosynthetic pathway, were able to restore heme levels to normal in yeast cells lacking Hem25 function. While neither glycine nor 5-Ala could ameliorate SLC25A38 congenital sideroblastic anemia in a zebrafish model, we determined that the addition of folate with glycine was able to restore hemoglobin levels. This difference is likely due to the fact that yeast can synthesize folate, whereas in zebrafish folate is an essential vitamin that must be obtained exogenously. Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia.

  1. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Xianchu Liu

    2016-04-01

    Full Text Available Objective(s:Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD. In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Materials and Methods:Diabetic rats were treated with naringin (100 mg/kg/d for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD and malondialdehyde (MDA] and inflammatory cytokines (TNF-a, IL-1β, and IL-6 were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT-PCR and Western blot analysis. Results:The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD.

  2. Cisplatin-induced renal inflammation is ameliorated by cilastatin nephroprotection.

    Science.gov (United States)

    Humanes, Blanca; Camaño, Sonia; Lara, Jose Manuel; Sabbisetti, Venkatta; González-Nicolás, María Ángeles; Bonventre, Joseph V; Tejedor, Alberto; Lázaro, Alberto

    2017-10-01

    Cisplatin is a potent chemotherapeutic drug whose nephrotoxic effect is a major complication and a dose-limiting factor for antitumoral therapy. There is much evidence that inflammation contributes to the pathogenesis of cisplatin-induced nephrotoxicity. We found that cilastatin, a renal dehydropeptidase-I inhibitor, has protective effects in vitro and in vivo against cisplatin-induced renal damage by inhibiting apoptosis and oxidation. Here, we investigated the potential use of cilastatin to protect against cisplatin-induced kidney injury and inflammation in rats. Male Wistar rats were divided into four groups: control, cilastatin-control, cisplatin and cilastatin-cisplatin. Nephrotoxicity was assessed 5 days after administration of cisplatin based on blood urea nitrogen, creatinine, glomerular filtration rate (GFR), kidney injury molecule (KIM)-1 and renal morphology. Inflammation was measured using the electrophoretic mobility shift assay, immunohistochemical studies and evaluation of inflammatory mediators. Compared with the control rats, cisplatin-administered rats were affected by significant proximal tubule damage, decreased GFR, increased production of inflammatory mediators and elevations in urea, creatinine and tissue KIM-1 levels. Cilastatin prevented these changes in renal function and ameliorated histological damage in cisplatin-administered animals. Cilastatin also reduced pro-inflammatory cytokine levels, activation of nuclear factor-κB and CD68-positive cell concentrations. Cilastatin reduces cisplatin-induced nephrotoxicity, which is associated with decreased inflammation in vivo. Although the exact role of decreased inflammation in nephroprotection has not been fully elucidated, treatment with cilastatin could be a novel strategy for the prevention of cisplatin-induced acute kidney injury. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  3. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

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    Wei Hu

    Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  4. Amelioration of acidic soil using various renewable waste resources.

    Science.gov (United States)

    Moon, Deok Hyun; Chang, Yoon-Young; Ok, Yong Sik; Cheong, Kyung Hoon; Koutsospyros, Agamemnon; Park, Jeong-Hun

    2014-01-01

    In this study, improvement of acidic soil with respect to soil pH and exchangeable cations was attempted for sample with an initial pH of approximately 5. Acidic soil was amended with various waste resources in the range of 1 to 5 wt.% including waste oyster shells (WOS), calcined oyster shells (COS), Class C fly ash (FA), and cement kiln dust (CKD) to improve soil pH and exchangeable cations. Upon treatment, the soil pH was monitored for periods up to 3 months. The exchangeable cations were measured after 1 month of curing. After a curing period of 1 month, a maize growth experiment was conducted with selected-treated samples to evaluate the effectiveness of treatment. The treatment results indicate that in order to increase the soil pH to a value of 7, 1 wt.% of WOS, 3 wt.% of FA, and 1 wt.% of CKD are required. In the case of COS, 1 wt.% was more than enough to increase the soil pH value to 7 because of COS's strong alkalinity. Moreover, the soil pH increases after a curing period of 7 days and remains virtually unchanged thereafter up to 1 month of curing. Upon treatment, the summation of cations (Ca, Mg, K, and Na) significantly increased. The growth of maize is superior in the treated samples rather than the untreated one, indicating that the amelioration of acidic soil is beneficial to plant growth, since soil pH was improved and nutrients were replenished.

  5. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-08-08

    deficiency of SIRT2 ameliorates iNOS, NO expression and reactive oxygen species production with suppressing LPS-induced activation of NFκB in macrophages.

  6. Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury.

    Science.gov (United States)

    Takasu, Chie; Vaziri, Nosratola D; Li, Shiri; Robles, Lourdes; Vo, Kelly; Takasu, Mizuki; Pham, Christine; Farzaneh, Seyed H; Shimada, Mitsuo; Stamos, Michael J; Ichii, Hirohito

    2017-07-07

    To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). Rats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. Histological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. DMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.

  7. Amelioration of the irrigated lands of the Vakhsh valley

    Science.gov (United States)

    Ikromov, Islomkul; Mirzoev, Mm

    2015-04-01

    In the agro-industrial country like Tajikistan, the efficient use of irrigation of arable land is important because it contributes to the solution of the State Program of the Food independence of the country, by increasing the yield of agricultural production per unit of irrigated area. The irrigated area in the Republic of Tajikistan as of 1.01.2014g. equal to about 750 thousand. ha, per capita, on average, less than 0.10 hectares. and its share in relation to agricultural land is only 10.5%. However, more than 90% of crop production are grown on these lands. Given the demographic growth of the population of the republic specific area of irrigated land from year to year is becoming less and less of that call into question the successful solution of the above program. Therefore, in our view, to ensure food independence of the country in addition to the development of land from the reserve, should focus on the amelioration of existing irrigated areas, improve the culture of land and water, on modernization of reclamation systems contribute to a high degree of adaptability based on a high degree of water metering, water distribution, water and resource conservation, the use of the latest technology and irrigation techniques. Condition of the soil is their estimated figures is mainly determined by its productivity. It is determined by the degree of salinity of soils, the depth of the groundwater level and salinity, erosion and on stony ground. Vakhsh valley in Tajikistan is one of the main oases, ensuring production of agricultural products but, in recent years due to a number of man-made reasons: Adherence crop irrigation, low technical condition of irrigation systems and as a consequence their efficiency and utilization of irrigation water and farming, inoperable drainage system, or lack of them all, the virtual absence of vodouchёta on the field, no use of it modern technology and irrigation techniques, etc., the level of both fresh and saline groundwater rose

  8. CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

    Science.gov (United States)

    Yu, Xiao-Wen

    Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

  9. Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species.

    Science.gov (United States)

    Jena, Ashish Kumar; Vasisht, Karan; Sharma, Neetika; Kaur, Ramdeep; Dhingra, Mamta Sachdeva; Karan, Maninder

    2016-08-22

    Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species. In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents. The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC. The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH. These findings are

  10. Assessment of changes of some functions of Ukrainian acid soils after chemical amelioration

    Directory of Open Access Journals (Sweden)

    Zapko Yurij

    2014-09-01

    Full Text Available The objective of the article was to determine the effectiveness of lime of different origin for chemical amelioration of soils and examine its impact on soil functions such as productivity, habitat, regulation of water quality, and the protective buffer biogeocenotic screen. Limy ameliorants were applied in small local field experiment on Luvic Chernozem, and experiment with lysimeter columns was carried out on Albic Luvisol. The number of the main groups of microflora and enzymatic activity of soil was determined in soil samples taken for the analysis from the root zone. Research concerning the influence of natural and industrial origin ameliorants on soil as habitat showed the correlation of sugar beets productivity with soil biogenic. The increase of biomultiplicity of soil microbiota after addition of a cement dust and negative influence of red sludge on soil as habitat for living organisms was observed. Research involving the influence of ameliorants on soil by lime as the protective buffer biogeocenotic screen was carried out using lysimeter columns. It was stated that the addition of limy ameliorants reduces mobility of heavy metals.

  11. The Effectiveness of Ameliorant to Increase Carbon Stock of Oilpalm and Rubber Plantation on Peatland

    Directory of Open Access Journals (Sweden)

    Ai Dariah

    2015-05-01

    Full Text Available Application of peatland amelioration can improve soil quality, reduce GHG emissions, and increase carbon sequestration. The research aimed to study the effect of peatland amelioration on oil palm and rubber carbon stock improvement. Research was conducted from August 2013 until June 2014. The researches on oil palm were done in Arang-arang Village, Kumpeh Subdistrict, Muaro Jambi District, and in Lubuk Ogong Village, Bandar Seikijang Sub-district, Pelalawan District. Both sites are in Jambi and Riau Province. The research on rubber was done in Jabiren Village, Jabiren Raya Subdistrict, Pulang Pisau District, Central Kalimantan Province. The study used a Randomized Completely Block Design (RCBD, in four treatments and four replications. The treatments were pugam (peat fertilizer enriched by polyvalent cation, manure; empty fruit bunch compost, and control (no application. The measurement of C stock was performed 10 months after application using nondestructive methods. The results showed that peatland amelioration treatments had no significant effect to improve C stock on oil palm in 6 years old and 7 years old of rubber. After 10 months of amelioration application, the treatments increased C - stock of oil palm and rubber were 2.1-2.4 Mg ha-1 and 5-11 Mg ha-1, respectively. Longer time observation may be needed to study the effect of ameliorant on C-stock of annual crops.

  12. Lipid abnormalities in streptozotocin-diabetes: Amelioration by Morus indica L. cv Suguna leaves

    OpenAIRE

    Andallu, B.; Vinay Kumar, A. V.; Varadacharyulu, N. Ch.

    2009-01-01

    AIM: To observe the influence of mulberry (Morus indica L. cv Suguna) leaves on lipid abnormalities in STZ-diabetic rats. MATERIALS AND METHODS: Treatment with dried mulberry leaf powder for a period of 8 weeks in hyperglycemic and hyperlipidemic STZ-diabetic rats. RESULTS: Mulberry leaves regulated fasting blood glucose, ameliorated the abnormalities in lipid profile as indicated by significant (P

  13. Amelioration of Tamoxifen-Induced Oxidative Stress in Rats | El Deib ...

    African Journals Online (AJOL)

    This study was conducted to investigate the ameliorative effect of silymarin on the oxidative stress induced by tamoxifen (TAM) in female albino rats. ... β- galactosidase (β-GAL) were significantly decreased in TAM-treated animals while concomitant treatment by silymarin caused marked decrease in the activities of the three ...

  14. Clinical Aspects of Pregnancy-induced Amelioration of Rheumatoid Arthritis: PARA-study

    NARCIS (Netherlands)

    Y.A. de Man (Yael)

    2009-01-01

    textabstractIn this PhD thesis, embedded in the PARA (Pregnancy-induced Amelioration of Rheumatoid Arthritis) study, several clinical aspects of the spontaneously occurring pregnancy-induced improvement of rheumatoid arthritis (RA) are addressed. An overview is given of inflammatory rheumatic

  15. Economic efficiency of the use of the bush vegetation from slopes of the ameliorative canals

    International Nuclear Information System (INIS)

    Titov, V.N.

    2009-01-01

    The results of calculations of the economic efficiency of the use of the bush vegetation from slopes of the ameliorative canals for fuel and energy purposes has been presented. The two variants of disposal of bushes are considered burning and conversion into fuel chips. (authors)

  16. A systematic review of the efficacy of gum chewing for the amelioration of postoperative ileus

    NARCIS (Netherlands)

    de Castro, S. M. M.; van den Esschert, J. W.; van Heek, N. T.; Dalhuisen, S.; Koelemay, M. J. W.; Busch, O. R. C.; Gouma, D. J.

    2008-01-01

    BACKGROUND: Recent trials have shown promising results for the efficacy of gum chewing for the amelioration of postoperative ileus. This finding could have a major clinical impact since gum chewing is relatively harmless and cheap while postoperative ileus has a significant impact on healthcare.

  17. Sodium fusidate (fusidin) ameliorates the course of monophasic experimental allergic encephalomyelitis in the Lewis rat

    DEFF Research Database (Denmark)

    Di Marco, R; Puglisi, G; Papaccio, G

    2001-01-01

    We have evaluated the effect of the immunosuppressant sodium fusidate (fusidin) on the course of acute monophasic experimental encephalomyelitis (EAE) in male Lewis rats. Prophylactic treatment with fusidin, 80 or 120 mg/kg bd wt., markedly ameliorated the course of the disease in rats immunized...

  18. Amelioration of Anti-Nutritive Effects of Castor Oil Seed ( Ricinus ...

    African Journals Online (AJOL)

    Three hundred and twenty (320) day old male broilers were used to investigate the amelioration of anti-nutritive effects of castor oil seed (Ricinus communis) meal in broilers' ration using natural fermentation and DL-Methionine supplementation. The experimental designed was a 4 × 2 factorial arrangement of dietary ...

  19. Sodium fusidate (fusidin) ameliorates the course of monophasic experimental allergic encephalomyelitis in the Lewis rat

    DEFF Research Database (Denmark)

    Di Marco, R; Puglisi, G; Papaccio, G

    2001-01-01

    We have evaluated the effect of the immunosuppressant sodium fusidate (fusidin) on the course of acute monophasic experimental encephalomyelitis (EAE) in male Lewis rats. Prophylactic treatment with fusidin, 80 or 120 mg/kg bd wt., markedly ameliorated the course of the disease in rats immunized ...

  20. EFFECTS OF AMELIORANT COMPOSITIONS ON NITROGEN MINERALIZATION AND UPTAKE BY SWEET CORN IN DEGRADED PEATLAND

    Directory of Open Access Journals (Sweden)

    Eni Maftu’ah

    2014-04-01

    Full Text Available Peat soil is characterized by poor nitrogen (N availability. Ameliorants are expected to rectify this problem. This research  aimed to study the effect of ameliorant on N availability and N uptake by sweet corn plant in degraded peatland. The experiment was conducted in the greenhouse in May-July 2011 and on peatland of Kalampangan Village, Palangkaraya, Central Kalimantan in September-December 2011. Burnt peat soil of Kalampangan was used in the greenhouse experiment and sweet corn was used as an indicator plant. The treatments consisted of two factors, i.e. compositions of ameliorants by weight (A1 = 80% chicken manure + 20% dolomite; A2 = 80% local farm weed + 20% dolomite; A3 = 80% mineral soil + 20% dolomite; A4 = 20% chicken manure + 20% local farm weed + 20% residue of Chinese water chestnut (Eleocharis dulcis + 20% mineral soil + 20% dolomite; and A5 = 19% chicken manure + 71.5% mineral soil + 9.5% dolomite and rates of those ameliorants (5, 10, 15, 20 and 25 t ha-1. The experiment was arranged in a completely randomized block design with three replications. Data were collected every two weeks for five times. Observations were made on soil pH, available N (NH4+, NO3-, plant height, and N uptake in root and shoot. The results showed that  treatment A1 increased soil pH and availability of NH4+ and NO3-  in peat soils at the maximum vegetative stage. Treatment A1 provided the highest N availability and N uptake by the plant. Field experiment showed that N uptake increased  with the plant yield. Optimum yield of fresh corn cob was obtained from treatment A1 at the rate of 20 t ha-1. This research reconfirms the effectiveness of chicken manure and dolomite as peat soil ameliorant.

  1. Characteristics of biomass ashes from different materials and their ameliorative effects on acid soils.

    Science.gov (United States)

    Shi, Renyong; Li, Jiuyu; Jiang, Jun; Mehmood, Khalid; Liu, Yuan; Xu, Renkou; Qian, Wei

    2017-05-01

    The chemical characteristics, element contents, mineral compositions, and the ameliorative effects on acid soils of five biomass ashes from different materials were analyzed. The chemical properties of the ashes varied depending on the source biomass material. An increase in the concrete shuttering contents in the biomass materials led to higher alkalinity, and higher Ca and Mg levels in biomass ashes, which made them particularly good at ameliorating effects on soil acidity. However, heavy metal contents, such as Cr, Cu, and Zn in the ashes, were relatively high. The incorporation of all ashes increased soil pH, exchangeable base cations, and available phosphorus, but decreased soil exchangeable acidity. The application of the ashes from biomass materials with a high concrete shuttering content increased the soil available heavy metal contents. Therefore, the biomass ashes from wood and crop residues with low concrete contents were the better acid soil amendments. Copyright © 2016. Published by Elsevier B.V.

  2. Deltamethrin Induced Alteration of Biochemical Parameters in Channa punctata, Bloch and its Amelioration by Quercetin.

    Science.gov (United States)

    Bhattacharjee, Parmita; Das, Suchismita

    2017-06-01

    We tested the impacts of pyrethroid pesticide deltamethrin and its amelioration by a flavonoid, quercetin, using tissue macromolecules (protein, amino acid, carbohydrate and glycogen) and antioxidant enzymes (superoxide dismutase, catalase and peroxidase) as biomarkers, on fish, Channa punctata, gill and liver. Our study proved that quercetin supplement alone, in the absence of pesticide, might be detrimental to fish health, in terms of depletion of major tissue macromolecules, but, such supplement may be beneficial to fish with pesticide associated oxidative stress. Multivariate analyses predicted that the antioxidant enzymes and lipid peroxidation were closely associated biomarkers; whereas tissue macromolecules formed a different cluster. Hence, oxidative stress biomarkers in fish can be considered a valuable tool in assessment of deltamethrin stress and its amelioration by quercetin. The work can pave the way for further research in establishing quercetin as a probable curative agent.

  3. Synthesis of Zirconia Nanoparticles and Their Ameliorative Roles as Additives Concrete Structures

    Directory of Open Access Journals (Sweden)

    Masoud Negahdary

    2013-01-01

    Full Text Available We investigated synthesis of zirconia nanoparticles (Nps and their ameliorative roles as additives concrete structures. Synthesized Zirconia Nps were studied with X-ray diffraction (XRD, UV-visible spectrophotometer, and transmission electron microscope (TEM. We used standard Portland cement in related experiment Concrete Structures. The experimental or E series (E1–E4 mixtures were prepared with different amounts of ZrO2 Nps with an average particle size of 20 nm. The experimental mixtures were prepared 0.125, 0.25, 0.5 and 2.0% ZrO2 Nps/cement by weight. The modified cement with ZrO2 nanoparticles was studied with split tensile strength, flexural strength and setting time methods. Final results showed that Zirconia Nps could be used for their Ameliorative roles as Additives Concrete Structures.

  4. Amelioration of soils contaminated with industrial exhalations in the Chvaletice region

    Energy Technology Data Exchange (ETDEWEB)

    Kozel, J.

    1966-01-01

    In the area of the Chvaletice manganese and pyrite works, the pyrite fly dust decomposing into sulfuric acid causes considerable damage to agricultural production. Sulfuric acid is also formed from the escaping sulfur dioxide. The reaction of the affected soils is extremely acid and reaches from 4.5 to 6.5 pH, and in some cases it decreases to 2.5 pH. Soil devastation spreads to distant land in the direction of the predominating winds. Damage is caused to agricultural crops which decreases yields. It was decided to ameliorate the affected soils with high doses of calcareous composts of material obtained from fish-ponds and of marl. The purpose of the experiment, the partial results of which are described, was an operational checking of the suitability of the composts for the amelioration of contaminated soils and an estimation of the doses to be applied.

  5. Lagenaria siceraria ameliorates atheromatous lesions by modulating HMG–CoA reductase and lipoprotein lipase enzymes activity in hypercholesterolemic rats

    Directory of Open Access Journals (Sweden)

    Mithun Singh Rajput

    2014-01-01

    Conclusion: It can be concluded that ethanolic extract of fruits of L. siceraria contains active components which ameliorates the atheromatous lesions in rat aorta and lowers the risk of atherosclerosis in hypercholesterolemic rats.

  6. Comment ameliorer la selection et le traitement des messages verbaux? (How to Improve the Selection and Processing of Verbal Messages)

    National Research Council Canada - National Science Library

    Rivenez, Marie; Darwin, Chris; Guillaume, Anne

    2005-01-01

    L'objectif de cette recherche est d'ameliorer la selection des messages verbaux. Nous cherchons a determiner les facteurs influencant le traitement d'un message verbal lorsque l'attention est portee sur un autre message...

  7. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in vitro studies against Aflatoxin B1 toxicity

    Directory of Open Access Journals (Sweden)

    Md. Sultan Ahmad

    2015-10-01

    Conclusion: Ameliorating potential of P. amarus was dose and duration dependant. These extracts significantly reduced the mutagenicity and genotoxicity that were produced due to AFB1 treatment both in vitro and in vivo.

  8. Ameliorative effect of antioxidants (vitamins C and E against abamectin toxicity in liver, kidney and testis of male albino rats

    Directory of Open Access Journals (Sweden)

    B. Wilson Magdy

    2016-10-01

    In conclusion, it appears that vitamins C and E, or in combination (as antioxidants ameliorate the hepato-renal and testicular toxicity of abamectin, but are not completely protective, especially in liver tissue.

  9. Treadmill Exercise Ameliorates Short-Term Memory Disturbance in Scopolamine-Induced Amnesia Rats

    OpenAIRE

    Heo, Yu-Mi; Shin, Mal-Soon; Lee, Jae-Min; Kim, Chang-Ju; Baek, Sang-Bin; Kim, Khae-Hawn; Baek, Seung-Soo

    2014-01-01

    Purpose Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice. Methods To induce amnesia, 1 mg/kg scopolamine hydrobro...

  10. Ala42S100A8 Ameliorates Psychological-Stress Impaired Cutaneous Wound Healing

    Science.gov (United States)

    Sroussi, Herve Y.; Williams, Richard L.; Zhang, Qing. L.; Villines, Dana.; Marucha, Phillip. T.

    2009-01-01

    Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation sensitive repellent of human neutrophils in-vitro. Ala42S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild type and ala42S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala42S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing. PMID:19336252

  11. “The Mind Is Its Own Place”: Amelioration of Claustrophobia in Semantic Dementia

    OpenAIRE

    Clark, Camilla N.; Downey, Laura E.; Golden, Hannah L.; Fletcher, Phillip D.; de Silva, Rajith; Cifelli, Alberto; Warren, Jason D.

    2014-01-01

    Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the brain basis of phobic responses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical syndrome of semantic dementia led by selective (predominantly right-sided) temporal lobe atrophy, who showed striking amelioration of previously disabling claustrophobia following onset of her cognitive syndrome. We interpret our patient's new...

  12. Use of vegetation to ameliorate building microclimates: an assessment of energy-conservation potentials

    Energy Technology Data Exchange (ETDEWEB)

    Hutchison, B.A.; Taylor, F.G.; Wendt, R.L.

    1982-04-01

    The space-conditioning energy conservation potentials of landscapes designed to ameliorate building microclimates are evaluated. The physical bases for vegetative modifications of climate are discussed, and results of past study of the effects of vegetation on space-conditioning energy consumption in buildings are reviewed. The state-of-the-art of energy-conserving landscape designs is assessed and recommendations are presented for further research.

  13. Effect of sodium fluoride in maternal and offspring rats and its amelioration

    Directory of Open Access Journals (Sweden)

    Sneha Panchal

    2014-03-01

    Full Text Available High fluoride content is known to cause dental and skeletal abnormalities. In addition, present review indicates that sodium fluoride consumption caused increased number of r=esorptions and dead foetuses. Various skeletal anomalies such as wavy ribs, presence of 14th ribs, lacking 6th sternebrae and incompete ossification of skull occur. All these changes could be due to oxidative stress caused by fluoride consumption. Fluoride-induced changes could be successfully ameliorated by cotreatment with vitamins and calcium.

  14. Simvastatin ameliorates established pulmonary hypertension through a heme oxygenase-1 dependent pathway in rats

    Directory of Open Access Journals (Sweden)

    Lee Yung-Chie

    2009-05-01

    Full Text Available Abstract Background Simvastatin has been shown to ameliorate pulmonary hypertension by several mechanisms in experimental animal models. In this study, we hypothesized that the major benefits of simvastatin in pulmonary hypertension occur via the heme oxygenase-1 pathway. Methods Simvastatin (10 mg/kgw/day was tested in two rat models of pulmonary hypertension (PH: monocrotaline administration and chronic hypoxia. The hemodynamic changes, right heart hypertrophy, HO-1 protein expression, and heme oxygenase (HO activity in lungs were measured in both models with and without simvastatin treatment. Tin-protoporphyrin (SnPP, 20 μmol/kg w/day, a potent inhibitor of HO activity, was used to confirm the role of HO-1. Results Simvastatin significantly ameliorated pulmonary arterial hypertension from 38.0 ± 2.2 mm Hg to 22.1 ± 1.9 mm Hg in monocrotaline-induced PH (MCT-PH and from 33.3 ± 0.8 mm Hg to 17.5 ± 2.9 mm Hg in chronic hypoxia-induced PH (CH-PH rats. The severity of right ventricular hypertrophy was significantly reduced by simvastatin in MCT-PH and CH-PH rats. Co-administration with SnPP abolished the benefits of simvastatin. Simvastatin significantly increased HO-1 protein expression and HO activity in the lungs of rats with PH; however co-administration of SnPP reduced HO-1 activity only. These observations indicate that the simvastatin-induced amelioration of pulmonary hypertension was directly related to the activity of HO-1, rather than its expression. Conclusion This study demonstrated that simvastatin treatment ameliorates established pulmonary hypertension primarily through an HO-1-dependent pathway.

  15. Secreted calmodulin-like skin protein ameliorates scopolamine-induced memory impairment.

    Science.gov (United States)

    Hayashi, Masaaki; Tajima, Hirohisa; Hashimoto, Yuichi; Matsuoka, Masaaki

    2014-06-18

    Humanin, a short bioactive peptide, inhibits cell death in a variety of cell-based death models through Humanin receptors in vitro. In vivo, Humanin ameliorates both muscarinic receptor antagonist-induced memory impairment in normal mice and memory impairment in Alzheimer's disease (AD)-relevant mouse models including aged transgenic mice expressing a familial AD-linked gene. Recently, calmodulin-like skin protein (CLSP) has been shown to be secreted from skin tissues, contain a region minimally similar to the core region of Humanin, and inhibit AD-related neuronal death through the heterotrimeric Humanin receptor on the cell surface in vitro. As CLSP is much more potent than Humanin and efficiently transported through blood circulation across the blood-brain barrier to the central nervous system, CLSP is considered as a physiological agonist that binds to the heterotrimeric Humanin receptor and triggers the Humanin-induced signals in central nervous system. However, it remains unknown whether CLSP ameliorates memory impairment in mouse dementia models as Humanin does. In this study, we show that recombinant CLSP, administered intracerebroventricularly or intraperitoneally, ameliorates scopolamine-induced dementia in mice.

  16. Role of exogenous and endogenous silicon in ameliorating behavioural responses to aluminium in a freshwater snail

    Energy Technology Data Exchange (ETDEWEB)

    Dobranskyte, A. [School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT (United Kingdom); Jugdaohsingh, R. [The Rayne Institute, St Thomas' Hospital, London (United Kingdom); Stuchlik, E. [Department of Hydrobiology, Charles University, Prague (Czech Republic); Powell, J.J. [Departments of Nutrition and Medicine, King' s College London (United Kingdom); White, K.N. [School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT (United Kingdom); McCrohan, C.R. [School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT (United Kingdom)]. E-mail: cathy.mccrohan@man.ac.uk

    2004-12-01

    Aluminium accumulation by the freshwater snail Lymnaea stagnalis is correlated with behavioural depression which is ameliorated by addition of orthosilicic acid. We hypothesised that Si is relocated to the digestive gland in response to Al, leading to the formation of non-toxic hydroxyaluminosilicates (HAS). Exposure to 500 {mu}g l{sup -1} Al for 30 days was associated with an initial period of behavioural depression, followed by apparent tolerance and subsequent depression, suggesting saturation of the cellular detoxification pathway during prolonged exposure. Exogenous Si (7.77 mg l{sup -1}) completely ameliorated all behavioural effects of Al but did not prevent its accumulation. In the presence of added Al, significantly more of this Si was accumulated by the tissues, compared to controls and snails exposed to Si alone. In snails exposed to Al plus Si, Al and Si concentrations were significantly correlated, with a ratio around 3:1 Al:Si, consistent with the presence of the non-toxic HAS protoimogolite. - Capsule: Toxicity of aluminium to freshwater snails is ameliorated by orthosilicic acid.

  17. Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice

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    Zhong-he Liu

    2015-01-01

    Full Text Available Objective. The effects of Flos Puerariae extract (FPE on cognitive impairment associated with diabetes were assessed in C57BL/6J mice. Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA and total cholesterol (TCH in serum, malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px, and acetylcholinesterase (AChE activities in cerebral cortex and hippocampus were also measured. Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE. Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

  18. β-glycosphingolipids ameliorated non-alcoholic steatohepatitis in the Psammomys obesus model

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    Zigmond E

    2014-10-01

    Full Text Available Ehud Zigmond,1,* Oshrat Tayer-Shifman,1,* Gadi Lalazar,1 Ami Ben Ya'acov,1 Sarah Weksler-Zangen,2 David Shasha,1 Miriam Sklair-Levy,3 Lidya Zolotarov,1 Zvi Shalev,1 Rony Kalman,2 Ehud Ziv,2 Itamar Raz,2 Yaron Ilan1 1Liver Unit, 2Diabetes Unit, 3Department of Radiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel *These authors contributed equally to this workAbstract: Liver steatosis is a common characteristic of obesity and type 2 diabetes, and fatty liver disease is increasingly recognized as a major health burden. Accumulating evidence suggests that β-glycosphingolipids play an important role in insulin sensitivity and thus could affect hepatic steatosis. To determine the effect associated with β-glycosphingolipid-mediated amelioration of liver injury, seven groups of Psammomys obesus on a high-energy diet were studied. Animals were treated with daily injections of β-glucosylceramide, β-lactosylceramide, or a combination of both. β-glycosphingolipids ameliorated the hepatic injury manifested by decreased liver enzymes, liver weight, and hepatic fat, and improved liver histology. Administration of both β-glucosylceramide and β-lactosylceramide also decreased interferon (IFN-γ serum levels. These effects were associated with improved serum cholesterol and triglyceride levels. These data suggest that β-glycosphingolipids ameliorate liver injury in an animal model of nonalcoholic steatohepatitis.Keywords: NAFLD, glycolipids, STAT, NASH, insulin resistance, diabetes

  19. Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy

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    Da Rae Kim

    2017-01-01

    Full Text Available Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. Methods. Mice were treated with normal saline (control, gemigliptin (GM, adriamycin (ADR, or adriamycin combined with gemigliptin (ADR+GM. Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

  20. Statin ameliorates endothelial dysfunction and insulin resistance in Tibet women with polycystic ovary syndrome.

    Science.gov (United States)

    Yang, B; Sun, Z-J; Chen, B; Zhang, J; Zhao, H; Li, C-W; Cao, Y-K; Cao, F

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In Tibet population, little is known about the correlation between PCOS and endothelial function and insulin resistance. In this study, we investigated the efficacy of simvastatin on ameliorating endothelial dysfunction and insulin resistance in Tibet patients with PCOS. A group of 21 PCOS women was compared with 21 age-paired controls for blood pressure, body mass index (BMI), lipids, glucose and insulin levels. Plasma ET-1 was quantitated using a commercially available ELISA kits. The invasive vascular endothelial function was evaluated through the measurement of brachial artery flow-mediated dilation (FMD) in the fasting state using high-resolution B-mode ultrasound and ankle-brachial index (ABI) by using a blood pressure cuff and a Doppler instrument. PCOS women had higher BMI (p Tibet PCOS patients present a clustering of atherosclerosis risk factors (obesity, adverse lipid profile, hypertension and hyperglycemia) and more prevalent in insulin resistance and endothelial dysfunction than non-PCOS women. The endothelial function and insulin resistance of PCOS patients were ameliorated The endothelial function and insulin resistance of PCOS patients were ameliorated after statin administration.

  1. The Ameliorative Effects of L-2-Oxothiazolidine-4-Carboxylate on Acetaminophen-Induced Hepatotoxicity in Mice

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    Jun Ho Shin

    2013-03-01

    Full Text Available The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC on acetaminophen (APAP-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH production and glutathione peroxidase (GSH-px activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.

  2. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  3. Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis.

    Science.gov (United States)

    Zhai, Mengen; Li, Buying; Duan, Weixun; Jing, Lin; Zhang, Bin; Zhang, Meng; Yu, Liming; Liu, Zhenhua; Yu, Bo; Ren, Kai; Gao, Erhe; Yang, Yang; Liang, Hongliang; Jin, Zhenxiao; Yu, Shiqiang

    2017-09-01

    Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the sirtuin family that is localized primarily to the mitochondria and protects against oxidative stress-related diseases, including myocardial ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R injury by activating the SIRT3 signaling pathway. In this study, mice were pretreated with or without a selective SIRT3 inhibitor and then subjected to MI/R operation. Melatonin was administered intraperitoneally (20 mg/kg) 10 minutes before reperfusion. Melatonin treatment improved postischemic cardiac contractile function, decreased infarct size, diminished lactate dehydrogenase release, reduced the apoptotic index, and ameliorated oxidative damage. Notably, MI/R induced a significant decrease in myocardial SIRT3 expression and activity, whereas the melatonin treatment upregulated SIRT3 expression and activity, and thus decreased the acetylation of superoxide dismutase 2 (SOD2). In addition, melatonin increased Bcl-2 expression and decreased Bax, Caspase-3, and cleaved Caspase-3 levels in response to MI/R. However, the cardioprotective effects of melatonin were largely abolished by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP), suggesting that SIRT3 plays an essential role in mediating the cardioprotective effects of melatonin. In vitro studies confirmed that melatonin also protected H9c2 cells against simulated ischemia/reperfusion injury (SIR) by attenuating oxidative stress and apoptosis, while SIRT3-targeted siRNA diminished these effects. Taken together, our results demonstrate for the first time that melatonin treatment ameliorates MI/R injury by reducing oxidative stress and apoptosis via activating the SIRT3 signaling pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons

  4. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  5. Amelioration of scopolamine-induced amnesia by phosphatidylserine and curcumin in the day-old chick.

    Science.gov (United States)

    Barber, Teresa A; Edris, Edward M; Levinsky, Paul J; Williams, Justin M; Brouwer, Ari R; Gessay, Shawn A

    2016-09-01

    In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day-old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state-dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease.

  6. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  7. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

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    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  8. Blonanserin, an antipsychotic and dopamine D₂/D₃receptor antagonist, and ameliorated alcohol dependence.

    Science.gov (United States)

    Takaki, Manabu; Ujike, Hiroshi

    2013-01-01

    Blonanserin (BNS) is used for treatment of both positive and negative symptoms of schizophrenia in Japan and Korea. Because BNS has weak α1 receptor blocking activities and is almost devoid of histamine H1 and muscarinic M1 antagonist activity, BNS is better tolerated than other atypical antipsychotics. A high degree of D₃ receptor blockage is reported to be predictive of drug abuse and alcoholism, and BNS has strong D₃ receptor antagonism. Thus, BNS may be useful in the treatment of alcoholism. We present a case in which BNS ameliorated alcohol dependence.

  9. Amelioration of soil PAH and heavy metals by combined application of fly ash and biochar

    Science.gov (United States)

    Masto, Reginald; George, Joshy; Ansari, Md; Ram, Lal

    2016-04-01

    Generation of electricity through coal combustion produces huge quantities of fly ash. Sustainable disposal and utilization of these fly ash is a major challenge. Fly ash along with other amendments like biochar could be used for amelioration of soil. In this study, fly ash and biochar were used together for amelioration of polycyclic aromatic hydrocarbon (PAH) contaminated soil. Field experiment was conducted to investigate the effects of fly ash and biochar on the amelioration of soil PAH, and the yield of Zea mays. The treatments were control, biochar (4 t/ha), fly ash (4 t/ha), ash + biochar ( 2 + 2 t/ha). Soil samples were collected after the harvest of maize crop and analysed for chemical and biological parameters. Thirteen PAHs were analysed in the postharvest soil samples. Soil PAHs were extracted in a microwave oven at 120 °C using hexane : acetone (1:1) mixture. The extracted solutions were concentrated, cleaned and the 13 PAHs [Acenaphthene (Ace), fluorene (Flr), phenanthrene (Phn), anthracene(Ant), pyrene(Pyr), benz(a)anthracene (BaA), chrysene (Chy), benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF), benzo(a)pyrene, benzo(g,h,i)perylene (BghiP), dibenzo(a,h)anthracene, and indeno(1,2,3-cd)pyrene)(Inp)] were analysed using GC-MS. The mean pH increased from 6.09 in control to 6.64 and 6.58 at biochar and fly ash treated soils, respectively. N content was not affected, whereas addition of biochar alone and in combination with fly ash, has significantly increased the soil organic carbon content. P content was almost double in combined (9.06 mg/kg) treatment as compared to control (4.32 mg/kg). The increase in K due to biochar was 118%, whereas char + ash increased soil K by 64%. Soil heavy metals were decreased: Zn (-48.4%), Ni (-41.4%), Co (-36.9%), Cu (-35.7%), Mn (-34.3%), Cd (-33.2%), and Pb (-30.4%). Soil dehydrogenase activity was significantly increased by ash and biochar treatments and the maximum activity was observed for the combined

  10. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

    Science.gov (United States)

    Ono, Taisuke; Takada, Shingo; Kinugawa, Shintaro; Tsutsui, Hiroyuki

    2015-09-01

    What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative

  11. Low-dose spironolactone ameliorates insulin resistance and suppresses elevated plasminogen activator inhibitor-1 during gestational testosterone exposure.

    Science.gov (United States)

    Olatunji, Lawrence A; Usman, Taofeek O; Akinade, Aminat I; Adeyanju, Oluwaseun A; Kim, InKyeom; Soladoye, Ayodele O

    2017-12-01

    Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life. We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects. Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19. Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone. These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.

  12. Gastrodia elata Ameliorates High-Fructose Diet-Induced Lipid Metabolism and Endothelial Dysfunction

    Directory of Open Access Journals (Sweden)

    Min Chul Kho

    2014-01-01

    Full Text Available Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF diet animal model. Rats were fed the 65% HF diet with/without EGB 100 mg/kg/day for 8 weeks. Treatment with EGB significantly suppressed the increments of epididymal fat weight, blood pressure, plasma triglyceride, total cholesterol levels, and oral glucose tolerance, respectively. In addition, EGB markedly prevented increase of adipocyte size and hepatic accumulation of triglycerides. EGB ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1 and adhesion molecules in the aorta. Moreover, EGB significantly recovered the impairment of vasorelaxation to acetylcholine and levels of endothelial nitric oxide synthase (eNOS expression and induced markedly upregulation of phosphorylation AMP-activated protein kinase (AMPKα in the liver, muscle, and fat. These results indicate that EGB ameliorates dyslipidemia, hypertension, and insulin resistance as well as impaired vascular endothelial function in HF diet rats. Taken together, EGB may be a beneficial therapeutic approach for metabolic syndrome.

  13. Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Géraldine H Petit

    Full Text Available Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

  14. Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease.

    Science.gov (United States)

    Petit, Géraldine H; Berkovich, Elijahu; Hickery, Mark; Kallunki, Pekka; Fog, Karina; Fitzer-Attas, Cheryl; Brundin, Patrik

    2013-01-01

    Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

  15. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

    Science.gov (United States)

    Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

    2017-01-01

    Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

  16. Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment.

    Science.gov (United States)

    Hota, Sunil Kumar; Barhwal, Kalpana; Baitharu, Iswar; Prasad, Dipti; Singh, Shashi Bala; Ilavazhagan, Govindasamy

    2009-04-01

    Hypobaric hypoxia induced memory impairment has been attributed to several factors including increased oxidative stress, depleted mitochondrial bioenergetics, altered neurotransmission and apoptosis. This multifactorial response of the brain to hypobaric hypoxia limits the use of therapeutic agents that target individual pathways for ameliorating hypobaric hypoxia induced memory impairment. The present study aimed at exploring the therapeutic potential of a bacoside rich leaf extract of Bacopa monniera in improving the memory functions in hypobaric conditions. The learning ability was evaluated in male Sprague Dawley rats along with memory retrieval following exposure to hypobaric conditions simulating an altitude of 25,000 ft for different durations. The effect of bacoside administration on apoptosis, cytochrome c oxidase activity, ATP levels, and oxidative stress markers and on plasma corticosterone levels was investigated. Expression of NR1 subunit of N-methyl-d-aspartate receptors, neuronal cell adhesion molecules and was also studied along with CREB phosphorylation to elucidate the molecular mechanisms of bacoside action. Bacoside administration was seen to enhance learning ability in rats along with augmentation in memory retrieval and prevention of dendritic atrophy following hypoxic exposure. In addition, it decreased oxidative stress, plasma corticosterone levels and neuronal degeneration. Bacoside administration also increased cytochrome c oxidase activity along with a concomitant increase in ATP levels. Hence, administration of bacosides could be a useful therapeutic strategy in ameliorating hypobaric hypoxia induced cognitive dysfunctions and other related neurological disorders.

  17. Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude-induced memory impairment.

    Science.gov (United States)

    Zhou, Baozhu; Li, Maoxing; Cao, Xinyuan; Zhang, Quanlong; Liu, Yantong; Ma, Qiang; Qiu, Yan; Luan, Fei; Wang, Xianmin

    2016-04-01

    Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Treadmill exercise ameliorates short-term memory disturbance in scopolamine-induced amnesia rats.

    Science.gov (United States)

    Heo, Yu-Mi; Shin, Mal-Soon; Lee, Jae-Min; Kim, Chang-Ju; Baek, Sang-Bin; Kim, Khae-Hawn; Baek, Seung-Soo

    2014-03-01

    Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice. To induce amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once per day for 14 days. A step-down avoidance test for short-term memory was conducted. AChE histochemistry, immunohistochemistry for collagen IV, and doublecortin were performed. Short-term memory deteriorated in the mice with scopolamine-induced amnesia, concomitant with enhanced AChE expression and suppression of angiogenesis in the hippocampus. Critically, treadmill exercise ameliorated short-term memory impairment, suppressed AChE expression, and enhanced angiogenesis in the mice with scopolamine-induced amnesia. Overexpression of AChE is implicated in both brain and renal disease. The findings of our study indicate that treadmill exercise may be of therapeutic value in neurodegenerative and renal diseases by suppressing the effects of AChE expression.

  19. Ameliorating effect of zhizi (Fructus gardeniae) extract and its glycosides on scopolamine-induced memory impairment.

    Science.gov (United States)

    Nam, Youngjoo; Lee, Dongung

    2013-04-01

    To study the chemical constituents of Zhizi (Fructus Gardeniae) and their antiamnesic effect in a mouse model of Alzheimer's disease. Ameliorating effects of the extracts, fractions and constituents on scopolamine-induced memory impairment in vivo using a passive avoidance task system and their inhibitory activities on acetylcholinesterase (AChE) in vitro were examined. The isolation of components was performed by chromatographic techniques and their structures were identified on the basis of spectral analysis. Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and crocin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition (43.4% at a final dose of 0.03 mg/mL) and also exhibited outstanding efficacy (65.9% at a dose of 250 mg/kg) in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activity and a potent ameliorating effect on scopolamine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. Geniposide, a main constituent of gardenia should be considered a candidate for further clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcholine enhancing cholinergic nervous system.

  20. Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury.

    Science.gov (United States)

    Han, Xiaodan; Xue, Xiaolei; Zhao, Yu; Li, Yuan; Liu, Weili; Zhang, Junling; Fan, Saijun

    2017-04-29

    Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress.

  1. Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats.

    Science.gov (United States)

    Zhang, Mingming; Zhou, Qian; Dorfman, Robert G; Huang, Xiaoli; Fan, Tingting; Zhang, Hao; Zhang, Jun; Yu, Chenggong

    2016-07-30

    Butyrate is an energy source for colonocytes that is formed by bacterial fermentation of dietary fiber in the colon and that exerts broad anti-inflammatory activities. Although the administration of butyrate improves homeostasis in patients and ameliorates IBD (Inflammatory Bowel Disease)-related lesions and symptoms, the anti-inflammatory mechanisms of butyrate still remain unclear. To explore the impact of butyrate on Treg (Regulatory T cell)/Th17 (T helper 17 cell) differentiation and colitis in rats. The effect of butyrate on the expression of markers related to both Tregs and Th17 cells were determined in human monocytes as well as a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. Rats were treated with butyrate in vivo, whereas the rat splenocytes and human monocytes were treated in vitro. We found that butyrate administration increased peripheral blood Treg cell levels as well as plasma levels of anti-Th17 cytokines (IL-10 and IL-12). Butyrate administration further suppressed IL-17 levels in both plasma and colonic mucosa, and ameliorated colonic colitis lesions in rats. This promotion of Treg activity and inhibition of IL-17 release was also observed in human venous monocytes and rat splenocytes in vitro. Our results suggest that butyrate plays a key role in regulating the Treg/Th17 balance and ultimately protects the colon mucosa against the development of IBD.

  2. Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats.

    Science.gov (United States)

    Wang, Jing-Hua; Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

    2017-09-22

    Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata , together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia , Akkermansia , and Gram-negative bacterium.

  3. Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model.

    Science.gov (United States)

    Dietrichs, Erik Sveberg; Kondratiev, Timofei; Tveita, Torkjel

    2014-12-01

    Rewarming from hypothermia is often complicated by cardiac dysfunction, characterized by substantial reduction in stroke volume. Previously we have reported that inotropic agents, working via cardiac β-receptor agonism may exert serious side effects when applied to treat cardiac contractile dysfunction during rewarming. In this study we tested whether Milrinone, a phosphodiesterase III inhibitor, is able to ameliorate such dysfunction when given during rewarming. A rat model designed for circulatory studies during experimental hypothermia with cooling to a core temperature of 15°C, stable hypothermia at this temperature for 3h and subsequent rewarming was used, with a total of 3 groups: (1) a normothermic group receiving Milrinone, (2) a hypothermic group receiving Milrinone the last hour of hypothermia and during rewarming, and (3) a hypothermic saline control group. Hemodynamic function was monitored using a conductance catheter introduced to the left ventricle. After rewarming from 15°C, stroke volume and cardiac output returned to within baseline values in Milrinone treated animals, while these variables were significantly reduced in saline controls. Milrinone ameliorated cardiac dysfunction during rewarming from 15°C. The present results suggest that at low core temperatures and during rewarming from such temperatures, pharmacologic efforts to support cardiovascular function is better achieved by substances preventing cyclic AMP breakdown rather than increasing its formation via β-receptor stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice

    Science.gov (United States)

    Diaz-Castroverde, Sabela; Gómez-Hernández, Almudena; Fernández, Silvia; García-Gómez, Gema; Di Scala, Marianna; González-Aseguinolaza, Gloria; Fernández-Millán, Elisa; González-Rodríguez, Águeda; García-Bravo, María; Chambon, Pierre; Álvarez, Carmen; Perdomo, Liliana; Beneit, Nuria; Benito, Manuel

    2016-01-01

    ABSTRACT Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte­-specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus. PMID:27562101

  5. Modafinil ameliorates cognitive deficits induced by maternal separation and sleep deprivation.

    Science.gov (United States)

    Garcia, Vanessa Athaíde; Hirotsu, Camila; Matos, Gabriela; Alvarenga, Tathiana; Pires, Gabriel Natan; Kapczinski, Flávio; Schröder, Nadja; Tufik, Sergio; Andersen, Monica Levy

    2013-09-15

    Animals exposed to an early adverse event may be more susceptible to a second source of stress later in life, and these stressors may have additive deleterious effects. Sleep deprivation is known to be a stressor, affecting multiple body functions such as the cognition. Modafinil enhances working memory and attention in healthy non-sleep deprived subjects and in animal models of sleep deprivation. The first aim of the present study was to investigate the effects of maternal separation (MS) combined with paradoxical sleep deprivation (PSD) in adulthood on recognition memory in rats. Second, we aimed to evaluate whether the administration of modafinil would be able to ameliorate memory deficits induced by MS and PSD. Wistar rat pups were initially distributed into MS and handling (H) groups, with their litters standardized in 4 females and 4 males. In adulthood, the male rats were submitted to PSD or control condition, being redistributed afterwards in modafinil- or vehicle-treatment immediately after the training session of object recognition task. PSD did not potentiate the cognitive deficit due to MS. However, modafinil was able to recover memory impairments associated to PSD and also to MS in the neonatal period. This study demonstrates for the first time that modafinil ameliorates cognitive deficits associated to MS and to PSD in adulthood, independent from MS in the neonatal period. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  7. Administration of heme arginate ameliorates murine type 2 diabetes independently of heme oxygenase activity.

    Directory of Open Access Journals (Sweden)

    Abhijeet K Choudhary

    Full Text Available Amelioration of rodent type 2 diabetes by hemin has been linked to increased heme oxygenase (HO activity, however alternative mechanisms have recently been proposed for its anti-diabetic effect. We sought to determine the anti-diabetic efficacy of heme arginate (HA, a clinically licensed preparation of heme, and whether its predominant mode of action is via increased HO activity. Intravenous administration of HA reduced hyperglycemia in diabetic (db/db mice. Co-administration of the HO inhibitor stannous (IV mesoporphyrin IX dichloride (SM resulted unexpectedly in a further improvement in glycaemic control despite restoring HO activity to baseline levels. The anti-diabetic effects of HA±SM were associated with increased adiposity, increased serum adiponectin levels, reduced adipose tissue and islet inflammation and preservation of islet β-cell function. HO activity independent effects of HA on adipogenesis and β-cell inflammation were further confirmed in cell culture models using the 3T3-L1 pre-adipocyte and MIN6 β-cell lines, respectively. In conclusion, our work demonstrates that the heme component of HA ameliorates experimental type 2 diabetes by promoting metabolically favourable adipogenesis and preserving islet β-cell function, but this is not mediated via increased HO activity.

  8. Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation.

    Science.gov (United States)

    Gupta, Amit Chand; Mohanty, Shilpa; Saxena, Archana; Maurya, Anil Kumar; Bawankule, Dnyaneshwar U

    2018-03-22

    Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

  9. Evaluation of promising technologies for soil salinity amelioration in Timpaki (Crete): a participatory approach

    Science.gov (United States)

    Panagea, I. S.; Daliakopoulos, I. N.; Tsanis, I. K.; Schwilch, G.

    2016-02-01

    Soil salinity management can be complex, expensive, and time demanding, especially in arid and semi-arid regions. Besides taking no action, possible management strategies include amelioration and adaptation measures. Here we apply the World Overview of Conservation Approaches and Technologies (WOCAT) framework for the systematic analysis and evaluation and selection of soil salinisation amelioration technologies in close collaboration with stakeholders. The participatory approach is applied in the RECARE (Preventing and Remediating degradation of soils in Europe through Land Care) project case study of Timpaki, a semi-arid region in south-central Crete (Greece) where the main land use is horticulture in greenhouses irrigated by groundwater. Excessive groundwater abstractions have resulted in a drop of the groundwater level in the coastal part of the aquifer, thus leading to seawater intrusion and in turn to soil salinisation. The documented technologies are evaluated for their impacts on ecosystem services, cost, and input requirements using a participatory approach and field evaluations. Results show that technologies which promote maintaining existing crop types while enhancing productivity and decreasing soil salinity are preferred by the stakeholders. The evaluation concludes that rainwater harvesting is the optimal solution for direct soil salinity mitigation, as it addresses a wider range of ecosystem and human well-being benefits. Nevertheless, this merit is offset by poor financial motivation making agronomic measures more attractive to users.

  10. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2018-01-11

    Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

  11. Climate change affecting oil palm agronomy, and oil palm cultivation increasing climate change, require amelioration.

    Science.gov (United States)

    Paterson, R Russell M; Lima, Nelson

    2018-01-01

    Palm oil is used in various valued commodities and is a large global industry worth over US$ 50 billion annually. Oil palms (OP) are grown commercially in Indonesia and Malaysia and other countries within Latin America and Africa. The large-scale land-use change has high ecological, economic, and social impacts. Tropical countries in particular are affected negatively by climate change (CC) which also has a detrimental impact on OP agronomy, whereas the cultivation of OP increases CC. Amelioration of both is required. The reduced ability to grow OP will reduce CC, which may allow more cultivation tending to increase CC, in a decreasing cycle. OP could be increasingly grown in more suitable regions occurring under CC. Enhancing the soil fauna may compensate for the effect of CC on OP agriculture to some extent. The effect of OP cultivation on CC may be reduced by employing reduced emissions from deforestation and forest degradation plans, for example, by avoiding illegal fire land clearing. Other ameliorating methods are reported herein. More research is required involving good management practices that can offset the increases in CC by OP plantations. Overall, OP-growing countries should support the Paris convention on reducing CC as the most feasible scheme for reducing CC.

  12. Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis

    Science.gov (United States)

    Lehert, Philippe; Villaseca, Paulina; Hogervorst, Eef; Maki, Pauline M.; Henderson, Victor W.

    2016-01-01

    A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually-modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For 10 of these, we used PubMed databases for a systematic review of long-duration (at least six months), randomized controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11 to 0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging. PMID:26361790

  13. Amelioration of experimental autoimmune encephalomyelitis in Lewis rats treated with fucoidan.

    Science.gov (United States)

    Kim, Heechul; Moon, Changjong; Park, Eun-jin; Jee, Youngheun; Ahn, Meejung; Wie, Myung Bok; Shin, Taekyun

    2010-03-01

    We examined whether fucoidan affected the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in rats. EAE was induced in Lewis rats that were immunized with guinea-pig myelin basic protein (MBP) and complete Freund's adjuvant. Fucoidan (50 mg/kg, daily) was administered to rats with EAE intraperitoneally, either in the EAE induction phase from either 1 day before immunization to day 7 post-immunization (PI), or the effector phase from day 8 to 14 PI, to test which phase of rat EAE is affected by fucoidan treatment.The onset, severity and duration of EAE paralysis in the fucoidan-treated group in the days 8-14 PI-treated rats, but not in days -1-7 PI-treated rats, were significantly delayed, suppressed and reduced, respectively, compared with the vehicle-treated controls. Treatment with fucoidan reduced the encephalitogenic response and TNF-alpha production during EAE. Moreover, the clinical amelioration coincided with decreased infiltration of inflammatory cells in the EAE-affected spinal cord. The ameliorative effect of fucoidan on clinical paralysis in EAE-affected rats may be mediated, in part, by the suppression of the autoreactive T cell response and inflammatory cytokine production. (c) 2009 John Wiley & Sons, Ltd.

  14. Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease

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    Naoya Matsunaga

    2016-11-01

    Full Text Available Chronic kidney disease (CKD is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2 ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif ligand 2 (Ccl2 was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK, did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

  15. Do antioxidant vitamins ameliorate the beneficial effects of exercise training on insulin sensitivity?

    Science.gov (United States)

    Lavie, Carl J; Milani, Jenna N

    2011-01-01

    Exercise training has numerous health benefits, and in patients with type 2 diabetes mellitus and metabolic syndrome, it can improve insulin sensitivity and glucose control. A recent publication suggests that antioxidant vitamins (C and E) block these effects on blood glucose. This investigation was undertaken to determine whether antioxidant vitamins ameliorate the beneficial effects of cardiac rehabilitation and exercise training (CRET) on insulin sensitivity and glucose metabolism in patients with coronary heart disease (CHD). We assessed CHD risk factors, including clinical indices of glucose metabolism, and evaluated the effects of exercise training in 315 patients with CHD with diabetes mellitus and/or metabolic syndrome before and after a 3-month program of CRET. Patients were divided into 2 groups based on self-reported antioxidant vitamin (vitamins C and E) consumption. Both groups, 113 patients (36%) consuming vitamins (Vits group) and 202 patients (64%) who reported no vitamin use (no-Vits group) were statistically similar at baseline. Following CRET, patients improved exercise capacity (10%, P vitamin E and 500 mg of vitamin C) do not ameliorate the health benefits of exercise training, including fasting blood glucose, in CHD patients

  16. Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice.

    Science.gov (United States)

    Chen, Zexian; He, Xiaowen; He, Xiaosheng; Chen, Xiuting; Lin, Xutao; Zou, Yifeng; Wu, Xiaojian; Lan, Ping

    2014-08-08

    Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD. MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed. MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment. MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Sustainable poverty amelioration through early life education in a peri-urban community of Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Olayinka A. Abosede

    2010-06-01

    Objectives: The aim of the study was to examine early life education for under-fives as a means of economic empowerment of mothers and sustainable poverty amelioration. Method: The methodology included a non-randomised selection of 34 disadvantaged mothers by criteria, a prospective intervention utilising community resources to organise early childhood education, an in-depth interview of mothers, and observation of the outcomes over a 5-year period. Results: The result of the study showed that no mother preferred keeping a child older than three years at home. Access to early childhood education gave mothers opportunity to undergo vocational training (1, 2.8% and take up new/additional jobs (12, 35.3%. All mothers and 32 (80% of the participating families more than doubled their income, earning up to twenty thousand Naira (approximately $182 per month from the first year of participation. Finally, selection criteria and periodic assessment of immunisation/growth monitoring records of participants’ children improved compliance with primary health care service utilisation. Conclusion: Organisation of early childhood education had the potential for sustainable poverty amelioration through economic empowerment of mothers.

  18. Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice.

    Science.gov (United States)

    Svensson, Kristoffer; Albert, Verena; Cardel, Bettina; Salatino, Silvia; Handschin, Christoph

    2016-05-01

    Ketone bodies (KBs) are crucial energy substrates during states of low carbohydrate availability. However, an aberrant regulation of KB homeostasis can lead to complications such as diabetic ketoacidosis. Exercise and diabetes affect systemic KB homeostasis, but the regulation of KB metabolism is still enigmatic. In our study in mice with either knockout or overexpression of the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α in skeletal muscle, PGC-1α regulated ketolytic gene transcription in muscle. Furthermore, KB homeostasis of these mice was investigated during withholding of food, exercise, and ketogenic diet feeding, and after streptozotocin injection. In response to these ketogenic stimuli, modulation of PGC-1α levels in muscle affected systemic KB homeostasis. Moreover, the data demonstrate that skeletal muscle PGC-1α is necessary for the enhanced ketolytic capacity in response to exercise training and overexpression of PGC-1α in muscle enhances systemic ketolytic capacity and is sufficient to ameliorate diabetic hyperketonemia in mice. In cultured myotubes, the transcription factor estrogen-related receptor-α was a partner of PGC-1α in the regulation of ketolytic gene transcription. These results demonstrate a central role of skeletal muscle PGC-1α in the transcriptional regulation of systemic ketolytic capacity.-Svensson, K., Albert, V., Cardel, B., Salatino, S., Handschin, C. Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice. © FASEB.

  19. Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent memory impairment in Fischer 344 rats.

    Science.gov (United States)

    Jeong, J-J; Woo, J-Y; Kim, K-A; Han, M J; Kim, D-H

    2015-04-01

    To understand the anti-inflammaging effect of lactic acid bacteria, we selected NF-κB activation-inhibitory Lactobacillus pentosus var. plantarum C29 and investigated its memory-enhancing and anti-inflammatory effects in aged Fischer 344 rats. C29 (2 × 10(9) CFU rat(-1) ), which was orally administered once a day (6 days per week) for 8 weeks, significantly restored age-reduced spontaneous alternation to 95.2% of that seen in young rats (P aged control rats. Oral administration of C29 restored age-reduced doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) expression and cAMP response element binding protein (CREB) activation in aged rats. Treatment of aged rats with C29 suppressed the expression of p16, cyclooxygenase-2, and inducible nitric oxide synthase, as well as the activation of Akt, mTOR, and NF-κB in the hippocampus. These findings suggest that C29 ameliorates ageing-dependent memory impairment by inhibiting NF-κB signalling pathway, inducing DCX and BDNF expression and activating CREB. The anti-inflammatory Lactobacillus pentosus var. plantarum C29 had the memory-enhancing effect in aged Fischer 344 rats by restoring doublecortin and brain-derived neurotrophic factor expression and suppressing p16 expression and NF-κB activation in the brain. Therefore, C29 may be useful in ameliorating age-related degenerative dementia. © 2015 The Society for Applied Microbiology.

  20. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    Science.gov (United States)

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Dietary Consumption of Virgin Coconut Oil Ameliorates Lipid Profiles in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    A. M. Akinnuga

    2014-01-01

    Full Text Available Virgin coconut oil (VCO is a saturated fat with promising antidiabetic properties but its ameliorative effect on lipid profiles in diabetics is rarely reported. Therefore, in this study, a total of fifteen (15 male rats weighing 200–250 g were divided into 3 experimental groups (n=5. Group I (control and Group II (diabetic control group were fed a normal rat chow while Group III (diabetic test group was fed a 10% VCO diet for 3 weeks. Group II and Group III were made diabetic by intraperitoneal injection of 150 mg/kg of alloxan. After 72 hours of injection, blood glucose was tested to confirm diabetes mellitus. After 3 weeks, the animals were sacrificed to collect blood samples for lipid profile analysis. The results showed a significant increase in concentrations of triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein and decrease in concentration of high density lipoprotein in Group II when compared to Group I. Also, the concentrations of triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein except high density lipoprotein significantly reduced in Group III when compared to Group II (P<0.01, 0.001. VCO consumption can be claimed to ameliorate lipid levels in diabetes mellitus.

  2. Phytoestrogen -zearalanol ameliorates memory impairment and neuronal DNA oxidation in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Yilong Dong

    2013-09-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer's disease-related memory impairment and neuronal oxidation in ovariectomized mice. METHODS: Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17β-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured. RESULTS: Treatment with 17β-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17β-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17β-estradiol or α-Zearalanol efficaciously ameliorated this situation. CONCLUSION: These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17β-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency.

  3. Electroacupuncture Ameliorates Cognitive Deficit and Improves Hippocampal Synaptic Plasticity in Adult Rat with Neonatal Maternal Separation

    Directory of Open Access Journals (Sweden)

    Lili Guo

    2018-01-01

    Full Text Available Exposure to adverse early-life events is thought to be the risk factors for the development of psychiatric and altered cognitive function in adulthood. The purpose of this study was to investigate whether electroacupuncture (EA treatment in young adult rat would improve impaired cognitive function and synaptic plasticity in adult rat with neonatal maternal separation (MS. Wistar rats were randomly divided into four groups: control group, MS group, MS with EA treatment (MS + EA group, and MS with Sham-EA treatment (MS + Sham-EA group. We evaluated the cognitive function by using Morris water maze and fear conditioning tests. Electrophysiology experiment used in vivo long-term potentiation (LTP at Schaffer Collateral-CA1 synapses was detected to assess extent of synaptic plasticity. Repeated EA stimulation at Baihui (GV 20 and Yintang (GV 29 during postnatal 9 to 11 weeks was identified to significantly ameliorate poor performance in behavior tests and improve the impaired LTP induction detected at Schaffer Collateral-CA1 synapse in hippocampus. Collectively, the findings suggested that early-life stress due to MS may induce adult cognitive deficit associated with hippocampus, and EA in young adult demonstrated that its therapeutic efficacy may be via ameliorating deficit of hippocampal synaptic plasticity.

  4. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa

    2012-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP in spontaneously hypertensive rats (SHR. It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2 and glutathione S-transferase (GST were significantly downregulated while total antioxidant status (TAS and activities of GST and catalase (CAT were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

  5. Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

    Science.gov (United States)

    Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

    2016-09-01

    Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

  6. Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of Symptom Amelioration and Ischemia Improvement

    Directory of Open Access Journals (Sweden)

    Youko Takakuwa

    2018-01-01

    Full Text Available Objective(s: The current management of coronary artery disease (CAD relies on three major therapeutic options, namely medication, percutaneous coronary intervention (PCI, and coronary artery bypass grafting (CABG. However, severe CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW therapy reported on human for the first time. This treatment resulted in better myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy, angina symptoms, and exercise tolerance. The aim of the present study was to investigate myocardial perfusion images and evaluate the relationship between the ischemia improvement and symptom amelioration by SW therapy. Methods: We treated ten patients (i.e., nine males and one female with cardiac SW therapy who had CAD but not indicated for PCI or CABG and aged 63–89 years old. After the SW therapy, all patients were followed up for three months to evaluate any amelioration of the myocardial ischemia based on symptoms, adenosine stress thallium scintigraphy, transthoracic echocardiography, and blood biochemical examinations. Results: The changes in various parameters were evaluated before and after cardiac SW therapy. The cardiac SW therapy resulted in a significant improvement in the symptoms as evaluated by the Canadian Cardiovascular Society [CCS] class score (P=0.016 and a tendency to improve in summed stress score (SSS (P=0.068. However, no significant improvement was observed in the summed rest score (SRS, summed difference score (SDS, left ventricular wall motion score index (LVWMSI, N-terminal pro-brain natriuretic, and troponin I. The difference of CCS class score (ΔCCS was significantly correlated with those of SSS (ΔSSS and SDS (ΔSDS (r=0.69, P=0.028 and r=0.70, P=0.025, respectively. There was no significant correlation between ΔCCS and other parameters. Furthermore, no significant

  7. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  8. The sustainable management of ameliorated peatlands on changed land use conditions; scenarios of constrains and possibilities

    Science.gov (United States)

    Shanskiy, , Merrit; Vollmer, Elis; Penu, Priit

    2015-04-01

    The utilization of organic soils for forestry or agriculture requires the land amelioration that could result on the peat losses from 15 to 20 t ha-1 in a year on following five years. After five years, the peat losses will be 5 - 15 t ha-1 in a year. The agricultural land resource on different types of organic soils (including ameliorated bogs) in Estonia is 360 000 ha that comprises 41% of total agricultural land area. The landscape iself is a valuable resource that considered to be a set of characteristics that satisfy needs of people using the landscape: economical or non-economical value; ecological, social, recreational, aesthetical, educational, scientific or even protective value. More diverse landscapes have higher biodiversity and yield more services to public, they are also seen as more sustainable and resilient to short-term changes. In order to maintain landscape diversity, sustainable maintenance is important. The purpose of current study was to estimate the land use potential on three different ameliorated peat areas and to develop the methodology for the futher sustainable utilization in order to secure the best ecological functioning of soil while taking into account maintaining and increasing landscape value. Therefore, site specific soil sampling (n=77) was carried out on predetermined eight study sites. Soil samples were analyzed for main agrochemical parameters (n=17; pHKCl, P, K, C%, N%, S%, ash, main anions and cations). This enables determing site-specific best suitable crops and land use scenarios. For the land resource description (soils type, topology) the digital soil map (1: 10,000) and field sudy based database were used for describing the model areas. For more specific identification of the field layers the Agricultural Registers and Information Board (ARIB) and databases of the Common Agricultural Policy (CAP) payments were used for subsidy schemes chekout. Estonian Nature Information System map tool was used to specify the

  9. Cyclosporine A, FK506, and NIM811 ameliorate prolonged CBF reduction and impaired neurovascular coupling after cortical spreading depression

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard; Witgen, Brent Marvin; Rasmussen, Peter

    2011-01-01

    ), and neurovascular and neurometabolic coupling were unaffected by all three drugs under control conditions. NIM811 augmented the rise in CBF observed during CSD. Cyclosporine A and FK506 ameliorated the persistent decrease in CBF after CSD. All three drugs prevented disruption of neurovascular coupling after CSD...

  10. Bezafibrate ameliorates diabetes via reduced steatosis and improved hepatic insulin sensitivity in diabetic TallyHo mice

    Directory of Open Access Journals (Sweden)

    Andras Franko

    2017-03-01

    Conclusions: Our data showed that BEZ ameliorates diabetes probably via reduced steatosis, enhanced hepatic mitochondrial mass, improved metabolic flexibility and elevated hepatic insulin sensitivity in TallyHo mice, suggesting that BEZ treatment could be beneficial for patients with NAFLD and impaired glucose metabolism.

  11. How to Cheat and Not Feel Guilty: Cognitive Dissonance and Its Amelioration in the Domain of Academic Dishonesty

    Science.gov (United States)

    Stephens, Jason M.

    2017-01-01

    The belief that cheating is wrong doesn't prevent its enactment. For example, many students cheat despite believing that is wrong or unjustifiable. The question taken up in this article concerns how the resulting cognitive dissonance is ameliorated; that is, how do students cheat and not feel guilty? This article will describe two "good"…

  12. Intestinal ameliorative effects of traditional Ogi-tutu, Vernonia amygdalina and Psidium guajava in mice infected with Vibrio cholera.

    Science.gov (United States)

    Shittu, Olufunke B; Ajayi, Olusola L; Bankole, Samuel O; Popoola, Temitope Os

    2016-06-01

    Cholera, a severe acute watery diarrhea caused by Vibrio cholerae is endemic in Nigeria with most cases occurring in the rural areas. In South West Nigeria, some individuals resort to alternative treatments such as Ogi-tutu, Psidium guajava and Vernonia amygdalina during infections. The effectiveness of these alternatives in the prevention and treatment of V. cholerae infection requires experimental investigation. This study was designed to investigate the ameliorative effects of Ogi-tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae. Preliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup diffusion assay. For ameliorative effects, adult mice were inoculated with 100 µl (106 cells) of Vibrio cholerae and dosed at 0 h (immediate prevention) and 4 h (treatment of infection) and their intestines were histopathologically evaluated. The histopathological changes were the same irrespective of the treated groups, but the lesions varied in extent and severity. The ameliorative effects in decreasing order were V. amygdalina > P. guajava > Ogi-tutu. V. amygdalina gave the best ameliorative effects in the prevention and treatment of V. cholerae infection.

  13. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders

    Directory of Open Access Journals (Sweden)

    Zhimin Chen

    2017-08-01

    Conclusions: Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD in patients.

  14. Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

    Science.gov (United States)

    Bhattacharya, Sanjib

    2017-12-01

    Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.

  15. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract

    International Nuclear Information System (INIS)

    Sinha, Mahuya; Das, Dipesh Kr; Dey, Sanjit; Datta, Sanjukta; Ghosh, Santinath

    2012-01-01

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60 Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. (author)

  16. “The Mind Is Its Own Place”: Amelioration of Claustrophobia in Semantic Dementia

    Science.gov (United States)

    Clark, Camilla N.; Downey, Laura E.; Golden, Hannah L.; Fletcher, Phillip D.; Cifelli, Alberto; Warren, Jason D.

    2014-01-01

    Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the brain basis of phobic responses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical syndrome of semantic dementia led by selective (predominantly right-sided) temporal lobe atrophy, who showed striking amelioration of previously disabling claustrophobia following onset of her cognitive syndrome. We interpret our patient's newfound fearlessness as an interaction of damaged limbic and autonomic responsivity with loss of the cognitive meaning of previously threatening situations. This case has implications for our understanding of brain network disintegration in semantic dementia and the neurocognitive basis of phobias more generally. PMID:24825962

  17. "The mind is its own place": amelioration of claustrophobia in semantic dementia.

    Science.gov (United States)

    Clark, Camilla N; Downey, Laura E; Golden, Hannah L; Fletcher, Phillip D; de Silva, Rajith; Cifelli, Alberto; Warren, Jason D

    2014-01-01

    Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the brain basis of phobic responses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical syndrome of semantic dementia led by selective (predominantly right-sided) temporal lobe atrophy, who showed striking amelioration of previously disabling claustrophobia following onset of her cognitive syndrome. We interpret our patient's newfound fearlessness as an interaction of damaged limbic and autonomic responsivity with loss of the cognitive meaning of previously threatening situations. This case has implications for our understanding of brain network disintegration in semantic dementia and the neurocognitive basis of phobias more generally.

  18. Seabuckthorn (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations

    International Nuclear Information System (INIS)

    Khan, Amitava; Manna, Krishnendu; Das, Dipesh Kr; Sinha, Mahuya; Kesh, Swaraj Bandhu; Das, Ujjal; Dey, Sanjit; Chinchubose; Banerji, Asoke; Dey, Rakhi Sharma

    2014-01-01

    In vitro assessment showed that H. rhumnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (γ) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of γ radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkB (p65) and IkBα: Ba increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures. (author)

  19. Amelioration of salt stress in wheat (triticum aestivum l.) by foliar application of nitrogen and potassium

    International Nuclear Information System (INIS)

    Odusote, O.O.; Alausa, S.K.; Gyang, B.N.

    2013-01-01

    An experiment was conducted in the Department of Biological Sciences, University of Sargodha, Pakistan. Different levels, viz. 0, 250, 500 mg/L, of nitrogen (N) and 0, 200, 400 mg/L of potassium (K) were applied exogenously as a foliar spray to determine whether application of N and K could ameliorate the effect of salinity stress on wheat (Triticum aestivum L.). It was composed of three replications. Each pot was filled with 8kg of well-mixed soil. Different salinity levels were adjusted in accordance with saturation percentage of soil. Salinity reduced the growth of wheat plants. When K and N were applied as foliar spray on the wheat plant, it reduced the effect of salinity and increased the plant growth and physiological attributes of wheat plants. Similarly, grains yield is also decreased by salinity but foliar application of K and N mitigated the salinity effect on grains yield. (author)

  20. AN AMELIORATED DETECTION STATISTICS FOR ADAPTIVE MASK MEDIAN FILTRATION OF HEAVILY NOISED DIGITAL IMAGES

    Directory of Open Access Journals (Sweden)

    Geeta Hanji

    2016-11-01

    Full Text Available Noise reduction is an important area of research in image processing applications. The performance of the digital image noise filtering method primarily depends upon the accuracy of noise detection scheme. This paper presents an effective detector based, adaptive mask, median filtration of heavily noised digital images affected with fixed value (or salt and pepper impulse noise. The proposed filter presents a novel approach; an ameliorated Rank Ordered Absolute Deviation (ROAD statistics to judge whether the input pixel is noised or noise free. If a pixel is detected as corrupted, it is subjected to adaptive mask median filtration; otherwise, it is kept unchanged. Extensive experimental results and comparative performance evaluations demonstrate that the proposed filter outperforms the existing decision type, median based filters with powerful noise detectors in terms of objective performance measures and visual retrieviation accuracy.

  1. THE AMELIORATION OF THE MUSCAT D´ADDA VARIETY THROUGH CLONE SELECTION

    Directory of Open Access Journals (Sweden)

    Stefania Iordache

    2010-01-01

    Full Text Available During the period 1983 – 1999, at INCDBH Stefanesti, the elite Mt. d´Adda 22 St. was selected and grown in contestplantations in order to be destined to the fresh grapevine consumption The identification of the biotypes(cloneshaving superior quality and production characteristics which manifest constantly, has been achieved through the studyof the elites chosen in comparative fields, using the method of repeated determinations in groups of years, underspecific vineyard conditions. Through repeated verification of the elites in the contest plots the elite Mt. d´Adda 22 St.stood out by superior quality, constant and sustained production of grapevines and the maintenance of the qualitycharacters. The elite was omologated in 2009. There had been identified and studied the clone elites which maintainedtheir productivity and quality characteristics during 2-3 years, which subsequently had been put to vegetativepropagation with a view to obtain the initial grafting material according to the intensive amelioration schemes.

  2. Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

    Science.gov (United States)

    Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

    2015-04-09

    Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

  3. Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.

    Science.gov (United States)

    Lee, In-Ah; Joh, Eun-Ha; Kim, Dong-Hyun

    2011-09-01

    The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p. o.) potently reversed scopolamine-induced memory deficits by 62 % and 73 %, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p. o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Mycofix ameliorative effect on Newcastle disease antibody production in broiler chickens during aflatoxicosis

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    M. T. Gargees

    2008-01-01

    Full Text Available Three experiments were conducted to elucidate the alleviation effects of Mycofix plus 3.0 on Newcastle antibody formation during aflatoxicosis in broiler chickens. Three levels of Mycofix (0.05%, 0.15%, and 0.25% and aflatoxin (2.5ppm, 3.5ppm, and 5ppm were used. Chickens were vaccinated at 8 and 18 days of age. Enzyme-linked immunosorbent assay and Haemagglutination inhibition tests were employed for determination Newcastle antibody titers at 28 days. The results showed that, Mycofix , and only at its high level of addition (0.25% was effective in ameliorating the negative effect of aflatoxin at the rates 2.5ppm and 3.5 ppm levels of inclusion on antibody production but not at the high level of 5ppm on antibody production, comparing with titers in control groups.

  5. Ameliorative effect of vitamin E on potassium dichromate-induced hepatotoxicity in rats

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    Ali A. Shati

    2014-07-01

    There was a significant accumulation of Cr in the livers of the Cr group compared with the control group. In addition, exposure to K2Cr2O7 induced significant increases in the level of thiobarbituric-reactive substances (TBARS and significant decreases in glutathione (GSH content and superoxide dismutase (SOD activity in the Cr group compared with the control group. Moreover, livers of the Cr group showed major histological alterations, such as severe necrosis, increased lymphocytic infiltration, and a significant decrease in the DNA content. Oral vitamin E administration concomitant with K2Cr2O7 ameliorated all these changes and resulted in normal hepatic histological and cellular contents. In conclusion, oral vitamin E administration has a hepatoprotective role against K2Cr2O7-induced hepatotoxicity in rats.

  6. Nigerian Honey Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Rats.

    Science.gov (United States)

    Erejuwa, Omotayo O; Nwobodo, Ndubuisi N; Akpan, Joseph L; Okorie, Ugochi A; Ezeonu, Chinonyelum T; Ezeokpo, Basil C; Nwadike, Kenneth I; Erhiano, Erhirhie; Abdul Wahab, Mohd S; Sulaiman, Siti A

    2016-02-24

    Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary to reduce cardiovascular events. Honey reduces hyperglycemia and dyslipidemia. The reproducibility of these beneficial effects and their generalization to honey samples of other geographical parts of the world remain controversial. Currently, data are limited and findings are inconclusive especially with evidence showing honey increased glycosylated hemoglobin in diabetic patients. It was hypothesized that this deteriorating effect might be due to administered high doses. This study investigated if Nigerian honey could ameliorate hyperglycemia and hyperlipidemia. It also evaluated if high doses of honey could worsen glucose and lipid abnormalities. Honey (1.0, 2.0 or 3.0 g/kg) was administered to diabetic rats for three weeks. Honey (1.0 or 2.0 g/kg) significantly (p honey (3.0 g/kg) significantly (p honey using Nigerian honey. However, none of the doses deteriorated hyperglycemia and dyslipidemia.

  7. Quercetin and omega 3 ameliorate oxidative stress induced by aluminium chloride in the brain.

    Science.gov (United States)

    Ali, Haytham Abdallah; Afifi, Mohamed; Abdelazim, Aaser Mohamed; Mosleh, Yahia Youssef

    2014-08-01

    Exposure to high levels of aluminum (Al) leads to neurodegeneration, which may be mediated through over-generation of free radicals. So, in the present study, we investigated the ability of both quercetin and omega 3 to ameliorate adverse effects of Al on brain antioxidants by monitoring the main brain antioxidant enzymes on molecular and cellular levels. The obtained results indicated that Al induced oxidative stress through induction of free radical production and inhibition of activity and expression of the antioxidant enzymes catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx); and at the same time induced superoxide dismutase (SOD) activity and gene expression. Both quercetin (QE) and omega 3 have the ability to overcome Al-induced oxidative stress, manifested by the significant reduction in free radical concentration and induction of the activity and gene expression of the brain antioxidant enzymes.

  8. Multisensory training reverses midbrain lesion-induced changes and ameliorates haemianopia.

    Science.gov (United States)

    Jiang, Huai; Stein, Barry E; McHaffie, John G

    2015-05-29

    Failure to attend to visual cues is a common consequence of visual cortex injury. Here, we report on a behavioural strategy whereby cross-modal (auditory-visual) training reinstates visuomotor competencies in animals rendered haemianopic by complete unilateral visual cortex ablation. The re-emergence of visual behaviours is correlated with the reinstatement of visual responsiveness in deep layer neurons of the ipsilesional superior colliculus (SC). This functional recovery is produced by training-induced alterations in descending influences from association cortex that allowed these midbrain neurons to once again transform visual cues into appropriate orientation behaviours. The findings underscore the inherent plasticity and functional breadth of phylogenetically older visuomotor circuits that can express visual capabilities thought to have been subsumed by more recently evolved brain regions. These observations suggest the need for reevaluating current concepts of functional segregation in the visual system and have important implications for strategies aimed at ameliorating trauma-induced visual deficits in humans.

  9. Using megestrol acetate to ameliorate protein-energy wasting in chronic kidney disease.

    Science.gov (United States)

    Smith, Christine Skouberdis; Logomarsino, John V

    2016-03-01

    Various populations are affected by chronic kidney disease (CKD), and a low dose appetite stimulant megestrol acetate (MA) is sometimes recommended in patients with CKD to ameliorate protein-energy wasting (PEW). Patients with CKD are at greater risk of developing PEW since the progression of their disease can cause decreased nutrient intake, catabolic effects, systemic inflammation and metabolic changes. Providers can detect PEW in CKD by identifying low serum levels ≤3.8 g/dl of albumin, protein and energy intake increases from 27% to 42%. There are potential adverse effects of using MA in CKD. After reviewing the available literature, the benefits of using MA should be evaluated against the potential side effects. For further examination of MA's potential benefits, long-term, prospective, large clinical trials should be carried out. © 2015 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  10. Smart Soup, a traditional Chinese medicine formula, ameliorates amyloid pathology and related cognitive deficits.

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    Yujun Hou

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS, a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT, Poria cum Radix Pini (PRP and Radix Polygalae (RP, is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease.

  11. Escitalopram ameliorates hypercortisolemia and insulin resistance in low birth weight men with limbic brain alterations

    DEFF Research Database (Denmark)

    Buhl, Christian Selmer; Stødkilde-Jørgensen, Hans; Videbech, Poul

    2017-01-01

    CONTEXT: Low birth weight (LBW, insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA)-axis hyperactivity. OBJECTIVE: First aim was to study insulin action, LHPA-axis function and limbic brain structures in young, healthy LBW-men vs. normal birth...... levels and improved Rdsubmax by ∼24% (p=0.04). CONCLUSIONS: LBW vs. NBW displayed alterations in key brain structures modulating LHPA-axis, elevated free cortisol levels and insulin resistance. Escitalopram administration ameliorated these defects, suggesting a potential for LHPA-axis modulation...... weight controls (NBW) (Part 1). Second aim was to investigate the effects of Escitalopram vs. placebo treatment in LBW with regards to LHPA-axis and insulin sensitivity (Part 2). DESIGN SETTING, PARTICIPANTS AND INTERVENTION: Maximal (Rdmax) and sub-maximal (Rdsubmax) rates of insulin-stimulated glucose...

  12. Amelioration of bromobenzene hepatotoxicity by Withania somnifera pretreatment: Role of mitochondrial oxidative stress

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    Mahima Vedi

    2014-01-01

    Full Text Available The present study investigated the possible protective role of Withania somnifera (Linn. Dunal (Solanaceae root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E. This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.

  13. Amelioration of bromobenzene hepatotoxicity byWithania somniferapretreatment: Role of mitochondrial oxidative stress.

    Science.gov (United States)

    Vedi, Mahima; Rasool, Mahaboobkhan; Sabina, Evan Prince

    2014-01-01

    The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.

  14. “The Mind Is Its Own Place”: Amelioration of Claustrophobia in Semantic Dementia

    Directory of Open Access Journals (Sweden)

    Camilla N. Clark

    2014-01-01

    Full Text Available Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the brain basis of phobic responses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical syndrome of semantic dementia led by selective (predominantly right-sided temporal lobe atrophy, who showed striking amelioration of previously disabling claustrophobia following onset of her cognitive syndrome. We interpret our patient’s newfound fearlessness as an interaction of damaged limbic and autonomic responsivity with loss of the cognitive meaning of previously threatening situations. This case has implications for our understanding of brain network disintegration in semantic dementia and the neurocognitive basis of phobias more generally.

  15. Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

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    Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Deng, Yubin, E-mail: dengyub@mail.sysu.edu.cn [Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Zeng, Mian, E-mail: zengmian2004@163.com [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)

    2016-05-20

    Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

  16. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

    Science.gov (United States)

    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level.

  17. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury.

    Science.gov (United States)

    Drommelschmidt, Karla; Serdar, Meray; Bendix, Ivo; Herz, Josephine; Bertling, Frederik; Prager, Sebastian; Keller, Matthias; Ludwig, Anna-Kristin; Duhan, Vikas; Radtke, Stefan; de Miroschedji, Kyra; Horn, Peter A; van de Looij, Yohan; Giebel, Bernd; Felderhoff-Müser, Ursula

    2017-02-01

    Preterm brain injury is a major cause of disability in later life, and may result in motor, cognitive and behavioural impairment for which no treatment is currently available. The aetiology is considered as multifactorial, and one underlying key player is inflammation leading to white and grey matter injury. Extracellular vesicles secreted by mesenchymal stem/stromal cells (MSC-EVs) have shown therapeutic potential in regenerative medicine. Here, we investigated the effects of MSC-EV treatment on brain microstructure and maturation, inflammatory processes and long-time outcome in a rodent model of inflammation-induced brain injury. 3-Day-old Wistar rats (P3) were intraperitoneally injected with 0.25mg/kg lipopolysaccharide or saline and treated with two repetitive doses of 1×10 8 cell equivalents of MSC-EVs per kg bodyweight. Cellular degeneration and reactive gliosis at P5 and myelination at P11 were evaluated by immunohistochemistry and western blot. Long-term cognitive and motor function was assessed by behavioural testing. Diffusion tensor imaging at P125 evaluated long-term microstructural white matter alterations. MSC-EV treatment significantly ameliorated inflammation-induced neuronal cellular degeneration reduced microgliosis and prevented reactive astrogliosis. Short-term myelination deficits and long-term microstructural abnormalities of the white matter were restored by MSC-EV administration. Morphological effects of MSC-EV treatment resulted in improved long-lasting cognitive functions INTERPRETATION: MSC-EVs ameliorate inflammation-induced cellular damage in a rat model of preterm brain injury. MSC-EVs may serve as a novel therapeutic option by prevention of neuronal cell death, restoration of white matter microstructure, reduction of gliosis and long-term functional improvement. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model

    Science.gov (United States)

    Jiang, Chun-Bin; Cheng, Mei-Lien; Liu, Chia-Yuan; Chang, Szu-Wen; Chiang Chiau, Jen-Shiu; Lee, Hung-Chang

    2015-01-01

    Background and Aims Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. Methods Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation. Results Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (Pprobiotics administration. We also found TNF-α, IL-1β and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1β: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (Pprobiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in the future. PMID:26406888

  19. Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.

    Science.gov (United States)

    Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota

    2017-11-01

    Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  20. Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats.

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    Baitharu, Iswar; Jain, Vishal; Deep, Satya Narayan; Hota, Kalpana Barhwal; Hota, Sunil Kumar; Prasad, Dipti; Ilavazhagan, Govindasamy

    2013-01-30

    Withania somnifera (WS) root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer and anti-stress agent. To evaluate the neuroprotective and prophylactic potential of WS root extract in ameliorating hypobaric hypoxia (HH) induced memory impairment and to explore the underlying molecular mechanism. WS root extract was administered to male Sprague Dawley rats during a period of 21 days pre-exposure and 07 days exposure to a simulated altitude of 25,000 ft. Spatial memory was assessed by Morris Water Maze. Neurodegeneration, corticosterone, acetylcholine (Ach) levels, acetylcholine esterase (AchE) activity, oxidative stress markers and nitric oxide (NO) concentration were assessed in the hippocampus. Synaptic and apoptotic markers were also investigated by immunoblotting. To study the role of NO in regulating corticosterone mediated signaling, the neuronal nitric oxide synthase (n-NOS) inhibitor, L-Nitro-arginine methyl ester (L-Name) and NO agonist sodium nitroprusside (SNP) were administered from 3rd to 7th day of hypoxic exposure. Administration of WS root extract prevented HH induced memory impairment and neurodegeneration along with decreased NO, corticosterone, oxidative stress and AchE activity in hippocampal region. Inhibition of NO synthesis by administration of L-Name reduced corticosterone levels in hippocampus during hypoxic exposure while co-administration of corticosterone increased neurodegeneration. Administration of sodium nitroprusside (SNP) along with WS root extract supplementation during hypoxic exposure increased corticosterone levels and increased the number of pyknotic cells. WS root extract ameliorated HH induced memory impairment and neurodegeneration in hippocampus through NO mediated modulation of corticosterone levels. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    Science.gov (United States)

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.

  2. Cognitive Ameliorating Effect of Acanthopanax koreanum Against Scopolamine-Induced Memory Impairment in Mice.

    Science.gov (United States)

    Lee, Sunhee; Park, Ho Jae; Jeon, Se Jin; Kim, Eunji; Lee, Hyung Eun; Kim, Haneul; Kwon, Yubeen; Zhang, Jiabao; Jung, In Ho; Ryu, Jong Hoon

    2017-03-01

    Acanthopanax koreanum Nakai (Araliaceae) is one of the most widely cultivated medicinal plants in Jeju Island, Korea, and the roots and stem bark of A. koreanum have been traditionally used as a tonic agent for general weakness. However, the use of A. koreanum for general weakness observed in the elderly, including those with declined cognitive function, has not been intensively investigated. This study was performed to investigate the effect of the ethanol extract of A. koreanum (EEAK) on cholinergic blockade-induced memory impairment in mice. To evaluate the ameliorating effects of EEAK against scopolamine-induced memory impairment, mice were orally administered EEAK (25, 50, 100, or 200 mg/kg), and several behavioral tasks, including a passive avoidance task, the Y-maze, and a novel object recognition task, were employed. Besides, western blot analysis was conducted to examine whether EEAK affected memory-associated signaling molecules, such as protein kinase B (Akt), Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), and cAMP response element-binding protein (CREB). The administration of EEAK (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in the passive avoidance task, the Y-maze, and the novel object recognition task. The phosphorylation levels of both Akt and CaMKII were significantly increased by approximately two-fold compared with the control group because of the administration of EEAK (100 or 200 mg/kg) (p memory-associated signaling molecules and may hold therapeutic potential against cognitive dysfunction, such as that presented in neurodegenerative diseases, for example, Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

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    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  4. Selenium ameliorates carbimazole induced hepatotoxicity and oxidative stress in Albino rats

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    Saber Abdel-Rahman Sakr

    2015-02-01

    Full Text Available Objective: To evaluate the effect of the antithyroid drug, carbimazole on liver of albino rats and the possible ameliorative role of selenium. Methods: Four groups of rats were used (n=10, Group 1 served as normal control, Group 2 was orally given sodium selenite (10 μg/kg body weight daily for 8 weeks, Group 3 was orally given carbimazole at a dose level of 1.35 mg/kg body weight, Group 4 was orally administered carbimazole and sodium selenite daily for 8 weeks. Rats in control and treated groups were sacrificed by cervical decapitation after 8 weeks of treatment, their livers were removed and stained with H&E for histological examinations. Alanine aminotransferase and aspartate aminotransferase were determined in the sera. Malondialdehyde and the antioxidant enzymes, catalase and superoxide dismutase were measured in the liver. Results: Cytoplasmic vacuolation of the hepatocytes, necrosis, leucocytic infiltrations, blood vessels congestion and fatty degeneration were observed in liver of carbimazole-treated animals. Carbimazole caused marked elevation in serum alanine aminotransferase and aspartate aminotransferase. It also caused an increase in malondialdehyde and depletion of the activity of the antioxidant enzymes, catalase and superoxide dismutase in the liver. Treating animals with carbimazole and selenium led to an improvement in both the histological and biochemical alterations induced by carbimazole. Moreover, selenium reduced the level of malondialdehyde and increased the activity of antioxidant enzymes, superoxide dismutase and catalase. Conclusions: It is concluded that the ameliorative effect of selenium against the hepatotoxicity of carbimazole is attributed to its antioxidant properties.

  5. Spironolactone ameliorates the cardiovascular toxicity induced by concomitant trastuzumab and thoracic radiotherapy.

    Science.gov (United States)

    Yavas, Guler; Celik, Esin; Yavas, Cagdas; Elsurer, Cagdas; Afsar, Rengin Elsurer

    2017-01-01

    We aimed to evaluate impact of spironolactone (S) on cardiovascular toxicity of concomitant use of radiotherapy (RT) and trastuzumab (T). S, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. S ameliorates anthracycline -induced cardiotoxicity, there is no data regarding to effect of S on both T and radiation-induced cardiotoxicity. Eighty rats were divided into eight groups: group (G) 1 was defined as control group. G2, G3 and G4 were RT, S and T groups respectively. G5, G6, G7 and G8 were RT + T, T + S, RT + S and RT + T + S groups respectively. Rats were sacrificed at 6th hour; 21st and 100th days after RT. Heart and thoracic aorta samples were taken for microscopical examination. Cardiac inflammation and fibrosis scores and; TGF-β expression were not significantly different within study groups at 6th hour and 21st days of RT. By 100th days of RT fibrosis scores and TGF-β expression in cardiac samples were significantly different between study groups (p values were 0.004 and 0.002 respectively). Pair-wise comparisons revealed that both cardiac fibrosis scores and TGF-β expression levels were higher in G5 when compared to G8 ( p values were 0.046 and 0.028 respectively). Moreover the TGF-β expression was higher in G5 when compared to G2 ( p  = 0.046). We could not demonstrate any significant differences with respect to inflammation, fibrosis and TGF-β expression in thoracic aorta samples between study groups. Although S had a protective effect on cardiac tissue it had no protective effect on thoracic aorta when administered with RT + T.

  6. GARLIC AMELIORATES THE HEPATOTOXIC EFFECT INDUCED BY THIOACETAMIDE IN FEMALE RATS

    International Nuclear Information System (INIS)

    OSMAN, H.F.; TAHA, M.S.

    2008-01-01

    The purpose of this study was to investigate the pretreatment effect of garlic on hepatotoxicity and oxidative stress induced by thioacetamide (TAA) in female albino rats.Sixty female adult albino rats were assigned equally into four groups; control group: animals without treatment, group ?: rats given daily oral dose of 250 mg/ kg garlic for 28 days, group ??: rats injected intraperitonealy by thioacetamide 20 mg ? kg for two weeks and group III: rats given 250 mg / kg garlic orally for 28 day followed by intrapertoneal injection of 20 mg / kg thioacetamide for two weeks. Liver enzymes were evaluated by measurements of AST, ALT and alkaline phosphatase and also trace elements (Cu and Zn) were estimated. Superoxide dismutase, glutathione peroxidase, malondialdehyde and thyroid hormones (T3 and T4) were assessed. Also, histological studies on liver and stomach were carried out. The results indicated that treatment with garlic significantly decreased liver enzymes (AST, ALT and ALP). Cu showed high significant increase in groups treated with garlic and also garlic + TAA, while Zn was increased significantly in TAA group. Superoxide dismutase (SOD) was increased significantly in group I while TAA decreased it significantly. Glutathione peroxidase was decreased significantly in group II while its level in group IV reached near the control value. Similarly, malondialdehyde was decreased significantly in garlic group and garlic ameliorated the thioacetamide effect in garlic + TAA group. The treatment with TAA led to significant increase in T3 and significant decrease in T4 hormones. Garlic ameliorated T3 level to reach the control level. Histologically, pre-treatment with garlic induced a prophylactic activity against the thioacetamide in liver and stomach tissues.According to the obtained results, it could be conclude that garlic treatment may act as antioxidant or pro-oxidant in TAA treated animals besides decreasing the TAA toxic effects on liver enzymes, liver and

  7. Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response.

    Science.gov (United States)

    Liu, Wen; Guo, Wenjie; Guo, Lele; Gu, Yanhong; Cai, Peifen; Xie, Ning; Yang, Xiaoling; Shu, Yongqian; Wu, Xuefeng; Sun, Yang; Xu, Qiang

    2014-06-01

    Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting condition of inflammation involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies for the treatment of IBD are desperately needed. In the present study, we aimed to examine the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Andrographolide sulfonate was administrated through intraperitoneal injection to mice with TNBS-induced colitis. TNBS-induced body weight loss, myeloperoxidase activity, shortening of the colon and colonic inflammation were significantly ameliorated by andrographolide sulfonate. Both the mRNA and protein levels of pro-inflammatory cytokines were reduced by andrographolide sulfonate administration. Moreover, andrographolide sulfonate markedly suppressed the activation of p38 mitogen-activated protein kinase as well as p65 subunit of nuclear factor-κB (NF-κB). Furthermore, CD4(+) T cell infiltration as well as the differentiation of Th1 (CD4(+)IFN-γ(+)) and Th17 (CD4(+)IL17A(+)) subset were inhibited by andrographolide sulfonate. In summary, these results suggest that andrographolide sulfonate ameliorated TNBS-induced colitis in mice through inhibiting Th1/Th17 response. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways.

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    Moonju Hong

    Full Text Available Shaofu Zhuyu decoction (SFZYD, also known as Sobokchugeo-tang, a classical prescription drug in traditional East Asian medicine, has been used to treat blood stasis syndrome (BSS. Hepatic steatosis is the result of excess caloric intake, and its pathogenesis involves internal retention of phlegm and dampness, blood stasis, and liver Qi stagnation. To evaluate the effects of treatment with SFZYD on obesity-induced inflammation and hepatic steatosis, we fed male C57BL/6N mice a high fat diet (HFD for 8 weeks and then treated them with SFZYD by oral gavage for an additional 4 weeks. The results of histological and biochemical examinations indicated that SFZYD treatment ameliorates systemic inflammation and hepatic steatosis. A partial least squares-discriminant analysis (PLS-DA scores plot of serum metabolites showed that HFD mice began to produce metabolites similar to those of normal chow (NC mice after SFZYD administration. We noted significant alterations in the levels of twenty-seven metabolites, alterations indicating that SFZYD regulates the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism. Increases in the levels of TCA cycle intermediate metabolites, such as 2-oxoglutaric acid, isocitric acid, and malic acid, in the serum of obese mice were significantly reversed after SFZYD treatment. In addition to inducing changes in the above metabolites, treatment with SFZYD also recovered the expression of genes related to hepatic mitochondrial dysfunction, including Ucp2, Cpt1α, and Ppargc1α, as well as the expression of genes involved in lipid metabolism and inflammation, without affecting glucose uptake or insulin signaling. Taken together, these findings suggest that treatment with SFZYD ameliorated obesity-induced systemic inflammation and hepatic steatosis by regulating inflammatory cytokine and adipokine levels in the circulation and various tissues. Moreover, treatment with SFZYD also reversed alterations in the

  9. Ameliorative Effect of Honey and Propolis Mixture on Rats Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Hemieda, S.F.; Abd-El Nour, K.N.; Hassan, A.I.; Abdou, M.I.; Khalil, W.A.

    2016-01-01

    This study aims to evaluate the ameliorative effect of honey and propolis mixture treatment on some biochemical and biophysical parameters in rats exposed to oxidative stress of gamma irradiation. Male rats were exposed to a fractionated dose gamma irradiation of total 5 Gy in five successive days. A mixture of dose 250 mg/kg/day honey and 90 mg/kg/day propolis was administrated to rats, ten days before irradiation, five days during irradiation and 14 days post irradiation. Blood samples were collected at 1 st , 7 th and 14 th day post the 5 th day of irradiation. Biochemical parameters such as serum liver enzymes (ALT and AST), serum renal function as (BUN and Creatinine) and serum total antioxidants were estimated. Also biophysical studies including hemoglobin investigations (Hb absorption spectra and dielectric measurements) were investigated.The results demonstrated that the levels of AST, ALT, BUN and creatinine were significantly elevated, while levels of total antioxidants were significantly reduced post irradiation. Moreover the absolute values of permittivity ε', dielectric loss ε'' and ac - conductivity σ ac increased in addition to a pronounced decrease in the absorbance at Sort band after irradiation compared to control group.Treatment of the irradiated group with honey and propolis mixture showed significant amelioration in the levels of the biochemical parameters. Also, the values of ε', ε'' and σ ac were nearly close to those of control group. Finally, the average value of peak height of Sort band was significantly increased compared to irradiated rat.

  10. Nigella Sativa and Panax Ginseng Supplementation Ameliorate Induced-Hyperlipidaemia in Male Rats

    International Nuclear Information System (INIS)

    Ezz El Arab, A.; El-Mahdy, A.A.; Abbas, O.A.

    2016-01-01

    The present work was conducted to study the effect of ginseng powder, ginseng oil, Nigella sativa seeds, Nigella sativa oil and combination of two oils on total cholesterol, triglycerides, adiponectin and some hormonal levels as testosterone. T3, T4 and serum glucose level in rats fed either normal chew or high fat diet. Nigella seed and oil, ginseng powder and oil and the combination of both oils decreased the highly level of cholesterol and triglycerides induced by fructose and high fat diet. The potent one was nigella seed. Nigella seed, Ginseng powder in addition to nigella and ginseng oils treatment ameliorate adiponectin suppression induced by high fat diet. Rats fed normal diet supplied with nigella oil, ginseng oil and both oils show a highly significant decrease in adiponectin level. Although nigella seed, nigella oil and the mixture of nigella and ginseng oils restored the hyperglycemia resulting from fructose administration to the normal level, but ginseng powder failed to affect this hyperglycemia. High fat diet increased T3 and T4 levels, nigella oil and ginseng powder treatment reduced T3 level, however nigella seed restored T4 level. Regarding the testosterone hormone, there was a significant increase in all hyperlipidaemic group that received ginseng and nigella compared to positive control.Ginseng powder increased testosterone in rats fed normal diet. In conclusion, administration of nigella and ginseng ameliorate the harmful changes in lipids and hormonal parameter induced by high fat diet. As in lowering blood lipids, improving adiponectin level and regulating the body basal metabolic rates by controlling thyroid hormones level as well as increase the testosterone level in hyperlipidaemic groups.

  11. Whole cell Deinococcus radiodurans ameliorates salt stress in Indian mustard through pyrroloquinoline quinone

    International Nuclear Information System (INIS)

    Srivastava, A.K.; Jadhav, P.; Suprasanna, P.; Rajpurohit, Y.S.; Misra, H.S.

    2015-01-01

    Salinity stress is considered as one of the major abiotic stresses limiting crop productivity. A variety of symbiotic and non-symbiotic bacteria are currently being used worldwide with the aim to boost built-in defense system in plants. Deinococcus radiodurans is a highly desiccation and radiation tolerant bacterium which synthesizes PQQ (pyrroloquinoline quinone) that has been shown to have a versatile role in crop productivity and as a general stress response regulator in bacteria and mammals. PQQ also acts as scavenger of reactive oxygen species and hence, can module redox signaling, one of the major regulator of stress tolerance in plants. In view of this, present research was conducted to evaluate the potential of whole cell D. radiodurans for ameliorating salt stress in plants. The soil colonization with wild-type cells led to partial amelioration of salt stress. The PQQ mutant showed an intermediate phenotype between wild-type seedlings and those grown on non-colonized soils which confirmed that the effects are largely associated with PQQ. The differential phenotype was also correlated with ROS level and ABA accumulation. The flame photometry data showed that there was no significant reduction in water soluble Na + level in control plant and those treated with either wild-type or PQQ mutant. Further, the elevated levels of antioxidant enzymes and reduced ascorbate in the plants treated with bacterial cells indicated its positive role in oxidative stress management. Although, the exact molecular basis to these effects is yet to be understood, present findings support the use of whole cell D. radiodurans for managing the growth and productivity of Indian mustard in salt affected fields. (author)

  12. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.

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    Marie Samanovic

    2009-01-01

    Full Text Available Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system.

  13. Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the amelioration of chronic constipation.

    Science.gov (United States)

    Inoue, Toshihiro; Takemura, Masaaki; Fushimi, Nobuhiko; Fujimori, Yoshikazu; Onozato, Tomoya; Kurooka, Takao; Asari, Tetsuya; Takeda, Hiroo; Kobayashi, Mamoru; Nishibe, Hironori; Isaji, Masayuki

    2017-07-05

    Chronic constipation is a highly common functional gastrointestinal disorder that adversely affects patient quality of life. At present, limited therapeutic options are available for the treatment of chronic constipation, which indicates the need for new therapeutic agents. Herein, we report the potential of mizagliflozin, a novel selective sodium glucose co-transporter 1 (SGLT1) inhibitor, for the amelioration of chronic constipation. Mizagliflozin's inhibitory activity against SGLTs was evaluated by an in vitro assay of cells transiently expressing SGLTs. The safety profile of an initial single dose (2-160mg, orally) and multiple doses (2-20mg, orally, once daily immediately prior to breakfast on Days 1 and 13, and three times daily immediately prior to every meal on Days 3-12) of mizagliflozin was determined by performing a phase I study in healthy male subjects. In addition, the effect of mizagliflozin and lubiprostone on fecal wet weight was compared using a dog model of loperamide-induced constipation and rat model of low-fiber-diet-induced constipation. Mizagliflozin potently inhibited human SGLT1 in a highly selective manner. The results of the phase I study showed mizagliflozin increased stool frequency and loosened stool consistency; these effects increased progressively with an increase in the dosage and the number of doses of mizagliflozin. In addition, the oral administration of mizagliflozin increased fecal wet weight in a dog model of loperamide-induced constipation and a rat model of low-fiber-diet-induced constipation, similar to lubiprostone. These results suggest the potential use of a novel selective SGLT1 inhibitor, mizagliflozin, for the amelioration of chronic constipation. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Nano-sized titanium dioxide toxicity in rat prostate and testis: Possible ameliorative effect of morin.

    Science.gov (United States)

    Shahin, Nancy N; Mohamed, Maha M

    2017-11-01

    This study investigated the effect of short-term oral exposure to nano-sized titanium dioxide (nTiO 2 ) on Wistar rat prostate and testis, and the associating reproductive-related alterations. The study also evaluated the potential ameliorative effect of the natural flavonoid, morin, on nTiO 2 -induced aberrations. Intragastric administration of nTiO 2 (50mg/kg/day for 1, 2 and 3weeks) increased testicular gamma-glutamyltransferase (γ-GT) activity and decreased testicular steroidogenic acute regulatory protein (StAR) and c-kit gene expression, serum testosterone level and sperm count. nTiO 2 -treated rats also exhibited prostatic and testicular altered glutathione levels, elevated TNF-α levels, up-regulated Fas, Bax and caspase-3 gene expression, down-regulated Bcl-2 gene expression and enhanced prostatic lipid peroxidation. Sperm malformation and elevated testicular acid phosphatase (ACP) activity and malondialdehyde level, serum prostatic acid phosphatase activity, prostate specific antigen (PSA), gonadotrophin and estradiol levels occurred after the 2 and 3week regimens. Morin (30mg/kg/day administered intragastrically for 5weeks) mitigated nTiO 2 -induced prostatic and testicular injury as evidenced by lowering serum PSA level, testicular γ-GT and ACP activities and TNF-α level, along with hampering both intrinsic and extrinsic apoptotic pathways. Moreover, morin alleviated prostatic lipid peroxidation, raised prostatic glutathione level, and relieved testicular reductive stress. Additionally, morin increased testicular StAR and c-kit mRNA expression, raised the sperm count, reduced sperm deformities and modified the altered hormone profile. Histopathological evaluation supported the biochemical findings. In conclusion, morin could ameliorate nTiO 2 -induced prostatic and testicular injury and the corresponding reproductive-related aberrations via redox regulatory, anti-inflammatory and anti-apoptotic mechanisms, promoting steroidogenesis and

  15. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

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    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  16. Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats.

    Science.gov (United States)

    Yuan, Fang; Liu, Ying-Hong; Liu, Fu-You; Peng, You-Ming; Tian, Jun-Wei

    2014-06-01

    The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.

  17. Utilizing Coal Ash and Humic Substances as Soil Ameliorant on Reclaimed Post-Mining Land

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    Ade Mariyam Oklima

    2014-09-01

    Full Text Available Coal ash and humic substances can be used as soil ameliorant in the reclamation of formerly mined land. Due to its high pH and nutrients content, coal ash can be used to improve the chemical properties of the soil, such as increasing of pH, and increasing the levels of nutrients availability in the soil. Humic substances may also be used to complement, as they can increase the release of nutrients from the coal ash. Thus, the objective of this study was to assess the influence of coal ash and humic substances on soil chemical characteristics, nutrient absorption, and plant growth. This study was conducted in two locations - in a nursery area, involving two treatment factors: coal ash at different dosages (0, 200, and 400 g polybag-1, and humic material also at varying dosages (0, 0.04, and 0.08 g C polybag-1; and in a post-mining field using similar treatments: coal ash dosage (0, 2.5, and 5.0 kg planting-1 hole and humic material dosage (0, 0.56, and 1.12 g C planting hole-1. The results showed that coal ash and humic materials significantly increased the soil pH, available P, and exchangeable K, Ca and Mg. Coal ash also contained a number of heavy metals but in quantities that are far below the limits set by both Indonesian Government Regulation and the US Environmental Protection Agency (USEPA. The above soil amelioration effects mean that. applicaton of coal ash and humic substances can significantly increase the growth of Jabon trees in the reclaimed post-mining land.

  18. Total saponin of Dioscoreae hypoglaucae rhizoma ameliorates streptozotocin-induced diabetic nephropathy

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    Guo C

    2016-02-01

    Full Text Available Changrun Guo,1 Gang Ding,2 Wenzhe Huang,2 Zhenzhong Wang,2 Zhaoqing Meng,1,2 Wei Xiao2 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang City, People’s Republic of China Background: Diabetic nephropathy has become the most common cause of morbidity and mortality in diabetic patients. Therefore, there is an urgent need for more effective and safer drugs for use in this condition.Purpose: The aims of this study were to investigate the ameliorative effects of total saponin of Dioscoreae hypoglaucae rhizoma (TSD on diabetic nephropathy and to explore the potential underlying mechanism(s.Methods: Rats with streptozotocin-induced diabetes were orally treated with TSD at 40, 80, and 160 mg/kg/d for 12 weeks. At the end of the treatment, blood, urine, and kidneys were collected for biochemical and histological examination.Results: The results demonstrated that TSD significantly decreased the fasting blood glucose, glycosylated hemoglobin, urinary protein, serum creatinine, and blood urea nitrogen levels in diabetic rats. The results of histological examinations showed that TSD ameliorated glomerular and tubular pathological changes in diabetic rats. Furthermore, TSD significantly prevented oxidative stress and reduced the renal levels of advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and tumor necrosis factor-α.Conclusion: This study demonstrated the renoprotective effects of TSD in experimental diabetic nephropathy via a number of different mechanisms. Keywords: total saponin of Dioscoreae hypoglaucae rhizoma, diabetic nephropathy, oxidative stress, AGEs, TGF-β1

  19. Ameliorating effects of tempol on methotrexate-induced liver injury in rats.

    Science.gov (United States)

    Pınar, Neslihan; Kaplan, Mahir; Özgür, Tümay; Özcan, Oğuzhan

    2018-03-28

    Methotrexate (MTX) is used in the treatment of certain types of cancers and chronic inflammatory illnesses, although the clinical use of MTX is limited due to its adverse effects, the most common of which are hepatotoxicity and nephrotoxicity. In the present study, we demonstrate the protecting influence of tempol related to oxidative stress in MTX-induced liver toxicity in rats using histopathological and biochemical parameters. The rats were divided into four groups: control group (group 1), tempol group (group 2), MTX group (group 3) and MTX + tempol group (group 4). The control group (group 1) received physiological saline for 10 days; the tempol group (group 2) received 30 mg/kg i.p. for 10 days, the MTX group (group 3) received a single dose of 20 mg/kg intraperitoneal (i.p.) on the fourth day of the study, and the MTX + tempol group (group 4) received a single dose of 20 mg/kg i.p. on the fourth day, followed by tempol 30 mg/kg i.p. for 10 days. Malondialdehyde (MDA), myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were found to be significantly lower in the MTX + tempol group then in the MTX group; while superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were found to be higher in the MTX + tempol group than in the MTX group. Tempol ameliorates vacuolic degeneration, inflammation and necrosis in MTX-treated rats. Our study demonstrates that tempol treatment after MTX administration ameliorates oxidative damage in liver tissue in rats. Copyright © 2018. Published by Elsevier Masson SAS.

  20. A Humanin Derivative Reduces Amyloid Beta Accumulation and Ameliorates Memory Deficit in Triple Transgenic Mice

    Science.gov (United States)

    Niikura, Takako; Sidahmed, Elkhansa; Hirata-Fukae, Chiho; Aisen, Paul S.; Matsuoka, Yasuji

    2011-01-01

    Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including exposure to amyloid beta (Abeta), in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APPswe, tauP310L, and PS-1M146V that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD. PMID:21264226

  1. A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice.

    Directory of Open Access Journals (Sweden)

    Takako Niikura

    Full Text Available Humanin (HN, a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD-related cytotoxicities, including exposure to amyloid beta (Abeta, in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APP(swe, tau(P310L, and PS-1(M146V that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD.

  2. Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells.

    Science.gov (United States)

    Yan, Ji-Jing; Jambaldorj, Enkthuya; Lee, Jae-Ghi; Jang, Joon Young; Shim, Jung Min; Han, Miyeun; Koo, Tai Yeon; Ahn, Curie; Yang, Jaeseok

    2016-11-15

    Granulocyte colony-stimulating factor (G-CSF) can induce regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSCs). Despite the immune modulatory effects of G-CSF, results of G-CSF treatment in systemic lupus erythematosus are still controversial. We therefore investigated whether G-CSF can ameliorate lupus nephritis and studied the underlying mechanisms. NZB/W F1 female mice were treated with G-CSF or phosphate-buffered saline for 5 consecutive days every week from 24 weeks of age, and were analyzed at 36 weeks of age. G-CSF treatment decreased proteinuria and serum anti-dsDNA, increased serum complement component 3 (C3), and attenuated renal tissue injury including deposition of IgG and C3. G-CSF treatment also decreased serum levels of BUN and creatinine, and ultimately decreased mortality of NZB/W F1 mice. G-CSF treatment induced expansion of CD4 + CD25 + Foxp3 + Tregs, with decreased renal infiltration of T cells, B cells, inflammatory granulocytes and monocytes in both kidneys and spleen. G-CSF treatment also decreased expression levels of MCP-1, IL-6, IL-2, and IL-10 in renal tissues as well as serum levels of MCP-1, IL-6, TNF-α, IL-10, and IL-17. When Tregs were depleted by PC61 treatment, G-CSF-mediated protective effects on lupus nephritis were abrogated. G-CSF treatment ameliorated lupus nephritis through the preferential expansion of CD4 + CD25 + Foxp3 + Tregs. Therefore, G-CSF has a therapeutic potential for lupus nephritis.

  3. Ghrelin ameliorates acute lung injury induced by oleic acid via inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Tian, Xiuli; Liu, Zhijun; Yu, Ting; Yang, Haitao; Feng, Linlin

    2018-03-01

    Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS) mediates the protective effect of ghrelin on ALI. We used a rat oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein levels were detected by western blot. Rats with OA treatment showed significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine release, hypoxia and CO 2 retention as compared with controls. Plasma and pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms, but treatment with the ghrelin antagonists D-Lys 3 GHRP-6 (1μmol/kg) and JMV 2959 (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm) prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt and Akt induced by OA was improved by ghrelin treatment, and was further exacerbated by ghrelin antagonists. Ghrelin protects against ALI by inhibiting ERS. These results provide a new target for prevention and therapy of ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Nigella sativa oil Ameliorates ionizing Radiation induced cellular injury in Male Albino Rats

    International Nuclear Information System (INIS)

    Mohamed, E.T.; El-Kady, A.A.

    2013-01-01

    Nigella sativa (NS), commonly known as black seed, is a plant spices in which thymoquinone is the main active ingredient isolated from the black seeds. The seeds of Nigella sativa are used in herbal medicine all over the world for the treatment and prevention of a number of diseases. The aim of this study was focused on investigating the possible protective effect of NS against gamma radiation induced nephrotoxicity and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole body gamma irradiation at a dose of 6 Gy), treated group (rats treated with 0.2 ml/kg, i.p., NS oil for 4 weeks), and treated irradiated group (animals treated with 0.2 mL/kg, i.p., NS oil for 4 weeks then exposed to whole body gamma irradiation at a dose of 6 Gy). The obtained results revealed that the administration of Nigella sativa oil to irradiated rats significantly ameliorated the changes induced in kidney antioxidant system; catalase and glutathione peroxidase activities as well as reduced glutathione concentration. Also, NS oil restored the kidney function indices (urea and creatinine) near normal level when compared with their equivalent values in irradiated rats. In addition, the changes in serum tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) activities were markedly improved compared to the corresponding values of irradiated group. The histopathological results showed distinctive pattern of ischemic renal injury in irradiated group, while in treated- irradiated group the renal tissues showed relatively well-preserved architecture with or without focal degeneration. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of gamma irradiation as shown in the biochemical and histopathological study and also NS oil might provide substantial protection against

  5. Glycoprotein 130 Inhibitor Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats.

    Science.gov (United States)

    Huang, Zhiwei; Liu, Zhihong; Luo, Qin; Zhao, Zhihui; Zhao, Qing; Zheng, Yaguo; Xi, Qunying; Tang, Yi

    2016-11-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, vascular remodelling, and microthrombotic events. Inflammatory cytokine interleukin (IL-6) may be a key factor in the development of PAH, and glycoprotein 130 (Gp130) is an important signal-transducing subunit of IL-6. The aim of our study was to evaluate the effectiveness of Gp130 inhibitor in reducing inflammation and ameliorating PAH-related vascular remodelling in monocrotaline (MCT)-exposed rats. Sprague-Dawley rats (n = 96; weight, 240-250 g) were randomly divided into 3 groups: control, MCT-exposed (MCT), and MCT-exposed plus Gp130 inhibitor (MCT-Gp) administered daily (5 mg/kg) from days 14-28. Eight rats were killed in each group at weeks 1 through 4, with the following measured variables compared across groups on day 28: hemodynamics, right ventricular hypertrophy, morphometric measurements, immunohistochemical results, levels of IL-6, phosphorylated signal transducer and activator of transcription 3, proliferating cell nuclear antigen (PCNA), bone morphogenetic protein receptor-2 (BMPR2), proangiogenic factor, vascular endothelial growth factor (VEGF), proproliferative kinase extracellular signal-regulated kinase (ERK), survivin, Bcl-2, and Bax. Compared with the MCT group, Gp130 inhibitor, after MCT exposure, improved hemodynamics and significantly reduced the severity of inflammation, as estimated by levels of IL-6 (P pulmonary arterial remodelling, as assessed by medial wall thickness (P pulmonary artery smooth muscle cell proliferation, and ameliorated pulmonary vascular remodelling in MCT-induced PH in rats. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  6. Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats.

    Science.gov (United States)

    Urakawa, Susumu; Takamoto, Kouichi; Nakamura, Tomoya; Sakai, Shigekazu; Matsuda, Teru; Taguchi, Toru; Mizumura, Kazue; Ono, Taketoshi; Nishijo, Hisao

    2015-02-01

    Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2-4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Jung, In Ho; Lee, Hyung Eun; Park, Se Jin; Ahn, Young Je; Kwon, Guyoung; Woo, Hyun; Lee, So Young; Kim, Ju Sun; Jo, Yeong-Woo; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

    2014-05-01

    Spinosin is a C-glycoside flavonoid isolated from the seeds of Zizyphus jujuba var. spinosa. This study investigated the effect of spinosin on cholinergic blockade-induced memory impairment in mice. Behavioral tests were conducted using the passive avoidance, Y-maze, and Morris water maze tasks to evaluate the memory-ameliorating effect of spinosin. Spinosin (10 or 20mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in these behavioral tasks with a prolonged latency time in the passive avoidance task, an increased percentage of spontaneous alternation in the Y-maze task and a lengthened swimming time in target quadrant in the Morris water maze task. In addition, a single administration of spinosin in normal naïve mice also enhanced the latency time in the passive avoidance task. To identify the mechanism of the memory-ameliorating effect of spinosin, receptor antagonism analysis and Western blotting were performed. The ameliorating effect of spinosin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose (0.5mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)tetralin, a 5-HT1A receptor agonist. In addition, spinosin significantly increased the expression levels of phosphorylated extracellular signal-regulated kinases and cAMP response element-binding proteins in the hippocampus. Taken together, these results indicate that the memory-ameliorating effect of spinosin may be, in part, due to the serotonergic neurotransmitter system, and that spinosin may be useful for the treatment of cognitive dysfunction in diseases such as Alzheimer's disease. Copyright © 2014. Published by Elsevier Inc.

  8. Changes in the properties of a crusty solonetz with soda salinization after single and repeated amelioration with phosphogypsum

    Science.gov (United States)

    Voropaeva, Z. I.; Trotsenko, I. A.; Parfenov, A. I.

    2011-03-01

    Different effects of single and repeated application of various rates of phosphogypsum to a crusty meadow chernozemic high-sodium solonetz with soda salinization formed in the zone of insufficient moistening in the forest-steppe zone of Western Siberia (the Ishim-Irtysh interfluve area) with the mean annual precipitation of 325 mm are revealed. Repeated phosphogypsum application provided a higher saturation of the soil exchange complex with exchangeable calcium, deeper desalinization of the soil profile, and more intensive removal of the exchange products beyond the 1-m-thick layer as compared to a single phosphogypsum application. The soil reclamation results in the soil profile's differentiation into three zones with respect to the salt content: the desalinization, transit, and accumulation zones. The greater the ameliorant rate, the higher the soil desalinization upon a single application of phosphogypsum. Upon the repeated phosphogypsum application, the zones of desalinization and salt transit are thicker irrespectively of the ameliorant rate. Despite the additional salt application, the degree of salinization in the upper 2 m does not increase. Data of the long-term investigations show that a single gypsum application exerts a favorable and long-term ameliorative effect. In the solonetz repeatedly ameliorated with phosphogypsum at the rates of 8 and 16 t/ha, the amount of the reacted phosphogypsum considerably exceeds the applied calculated rate and is almost equal to that upon a single application of phosphogypsum at the double rate (32 t/ha). It has been shown that not only the repeatedly applied phosphogypsum but also the soil calcium participates in the exchange reactions. This makes it possible to apply smaller rates of the ameliorant or calculate its rate for the upper 10-cm-thick layer.

  9. Lactobacillus plantarum MYS6 Ameliorates Fumonisin B1-Induced Hepatorenal Damage in Broilers

    Directory of Open Access Journals (Sweden)

    B. V. Deepthi

    2017-11-01

    Full Text Available Fumonisin B1 (FB1, a mycotoxin produced by Fusarium species is a predominant Group 2B carcinogen occurring in maize and maize-based poultry feeds. It is shown to be nephrotoxic, hepatotoxic, neurotoxic, and immunosuppressing in animals. In this study, we report the ameliorating effects of a probiotic strain, Lactobacillus plantarum MYS6 on FB1-induced toxicity and oxidative damage in broilers. A 6-week dietary experiment consisting of 48 broilers was performed in six treatment groups. Probiotic treatment (109 cells/mL involved pre-colonization of broilers with L. plantarum MYS6 while co-administration treatment involved supplementation of probiotic and FB1-contaminated diet (200 mg/Kg feed simultaneously. At the end of the treatment period, growth performance, hematology, serum biochemistry, and markers of oxidative stress in serum and tissue homogenates were evaluated in all the broilers. The histopathological changes in hepatic and renal tissues were further studied. The results demonstrated that administration of L. plantarum MYS6 efficiently improved the feed intake, body weight and feed conversion ratio in broilers. It mitigated the altered levels of hematological indices such as complete blood count, hemoglobin, and hematocrit. Serum parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, creatinine, cholesterol, triglycerides, and albumin were significantly restored after administering the probiotic in FB1-intoxicated broilers. Additionally, L. plantarum MYS6 alleviated the levels of oxidative stress markers in serum and tissue homogenate of liver. The histopathological data of liver and kidney further substantiated the overall protection offered by L. plantarum MYS6 against FB1-induced cellular toxicity and organ damage in broilers. Our results indicated that co-administration of probiotic along with the toxin had better effect in detoxification compared to its pre-colonization in broilers

  10. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  11. Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

    Science.gov (United States)

    Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

    2015-06-01

    Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. High fructose feeding to rats and hamsters led to the development of insulin

  12. PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes.

    Science.gov (United States)

    Chen, Fu-Chih; Shen, Kuo-Ping; Chen, Jin-Bor; Lin, Hui-Li; Hao, Chi-Long; Yen, Hsueh-Wei; Shaw, Shyh-Yu

    2018-01-01

    Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-α (PI3K-α), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-α (PPAR-α) and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance. Copyright © 2017. Published by Elsevier Taiwan.

  13. Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat

    Directory of Open Access Journals (Sweden)

    Vishal Singh

    2015-01-01

    Full Text Available Background & objectives: Curcuma oil (C. oil isolated from turmeric (Curcuma longa L. has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg or C. oil (300 mg/kg in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c, peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation

  14. The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

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    Nermin Eissa

    2018-02-01

    Full Text Available The role of Histamine H3 receptors (H3Rs in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP and novel object recognition (NOR task in adult male rats, using donepezil (DOZ as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p. significantly ameliorated memory deficits induced with MK801 in PAP (all P < 0.05, n = 7. The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p. was reversed when rats were co-injected with the H3R agonist R-(α-methylhistamine (RAMH, 10 mg/kg, i.p. (p = 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group, n = 6. In the NOR paradigm, DL77 (5 mg/kg, i.p. counteracted long-term memory (LTM deficits induced with MK801 (P < 0.05, n = 6–8, and the DL77-provided effect was similar to that of DOZ (p = 0.788, n = 6–8, and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p. (p = 0.877, n = 6, as compared to the (MK801-amnesic group. However, DL77 (5 mg/kg, i.p. did not alter short-term memory (STM impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801-amnesic group. Moreover, DL77 (5 mg/kg failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6, demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating

  15. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

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    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  16. PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes

    Directory of Open Access Journals (Sweden)

    Fu-Chih Chen

    2018-01-01

    Full Text Available Pre-germinated brown rice (PGBR could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml. The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK, insulin receptor substrate-1 (IRS-1, phosphatidylinositol-3-kinase-α (PI3K-α, serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB, glucose transporter-2 (GLUT-2, glucokinase (GCK, peroxisome proliferator activated receptor-α (PPAR-α and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2 which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3, PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance.

  17. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

    Science.gov (United States)

    Qu, Chang; Yuan, Zhong-Wen; Yu, Xiu-Ting; Huang, Yan-Feng; Yang, Guang-Hua; Chen, Jian-Nan; Lai, Xiao-Ping; Su, Zi-Ren; Zeng, Hui-Fang; Xie, Ying; Zhang, Xiao-Jun

    2017-07-01

    Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C 15 H 26 O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given

  18. Ameliorative properties of Iranian Trigonella foenum-graecum L. seeds and Punica granatum L. peel extracts in streptozotocin-induced experimental diabetic guinea pigs

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    Nabil Abdel Salam Ahmed Hasona

    2017-03-01

    Conclusions: The Iranian T. foenum-graecum seeds and P. granatum peel extracts are significantly potent in ameliorating diabetic condition induced by streptozotocin and improving various biochemical parameters in serum and liver of guinea pigs.

  19. Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

    OpenAIRE

    Himeno, Tatsuhito; Kamiya, Hideki; Naruse, Keiko; Cheng, Zhao; Ito, Sachiko; Kondo, Masaki; Okawa, Tetsuji; Fujiya, Atsushi; Kato, Jiro; Suzuki, Hirohiko; Kito, Tetsutaro; Hamada, Yoji; Oiso, Yutaka; Isobe, Kenichi; Nakamura, Jiro

    2013-01-01

    Background. Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSC...

  20. Modelling of {sup 137}Cs behaviour in the soil-plant system following the application of ameliorants

    Energy Technology Data Exchange (ETDEWEB)

    Spiridonov, S.; Fesenko, S.; Sanzharova, N. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2004-07-01

    A set of countermeasures aimed at reducing {sup 137}Cs uptake by plant products includes agrochemical measures based on changes in the soil properties after the application of ameliorants. The dynamic models for studying the effect of the application of potassium fertilizers and dolomite powder on {sup 137}Cs accumulation in plants are presented. Conceptual approaches to the development of models are based on the identification of mechanisms governing a complex of physico-chemical processes in soil after the use of ameliorants. The following assumptions were used in the development of models: - dynamics of {sup 137}Cs distribution in each soil layer depends on the sorption processes characterized by different time to achieve quasi-equilibrium (exchangeable uptake and fixation by clay minerals) as well as on vertical migration process; - change in {sup 137}Cs content in soil solution results from the radionuclide sorption on selective and nonselective exchange sites; - uptake of extra amounts of K{sup +} and Ca{sup 2+} in soil solution produces effect on processes of {sup 137}Cs exchangeable sorption and initiate specific processes responsible for {sup 137}Cs fixation in the crystal lattice of clay minerals; - Ca{sup 2+} and K{sup +} cations have a competing effect on {sup 137}Cs uptake by plants from soil solution, which along with the fixation processes, causes lower accumulation of this radionuclide by plants during the application of ameliorants. The developed models were parameterized for soils of the coniferous forest located in the Bryansk region in area suffered from the radioactive fallout after the Chernobyl accident. Effects of ameliorants and time of their application on {sup 137}Cs behaviour in the soil-plant system are assessed. The contribution of soil chemical and biological processes to the decrease in the radionuclide uptake by plants is estimated. (author)

  1. PARTIALLY HYDROLYZED GUAR GUM INTAKE AMELIORATES CONSTIPATION, IMPROVES NUTRITIONAL STATUS AND REDUCES INDOXYLSULFURIC ACID IN DIALYSIS PATIENTS.

    OpenAIRE

    Maeda, Hiroto; Uemura, Tomoko; Nasu, Makoto; Iwata, Natsumi; Yoshimura, Junko; Sakai, Shoji

    2012-01-01

    Dialysis patients often develop constipation and changes in intestinal bacterial flora. Indoxylsulfuric acid (IS) levels rise as glomerular filtration decreases, and patients with renal failure have high IS. Elevated IS is also caused by increased indole due to altered intestinal flora (Takayama et al, Am J Kidney Dis. 2003). We investigated whether administering partially hydrolyzed guar gum (PHGG) (Sunfiber: a product of Taiyokagaku Co., Ltd., Japan) ameliorates constipation and improves nu...

  2. Ameliorative effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient young mice.

    Science.gov (United States)

    Tamano, Haruna; Kan, Fumika; Oku, Naoto; Takeda, Atsushi

    2010-11-20

    Yokukansan, a traditional Japanese medicine has been used to cure neuropsychological disorders. In the present study, the effect of Yokukansan on social isolation-induced aggressive behavior was examined in zinc-deficient mice, which were fed a zinc-deficient diet and a drinking water containing Yokukansan for 2 weeks. In the resident-intruder test, the rate of mice that exhibited aggressive behavior in zinc-deficient mice, which was significantly higher than that in the control mice, was significantly decreased by administration of Yokukansan. The basal level of serum glucocorticoid, which was significantly higher in zinc-deficient mice, was lowered by administration of Yokukansan. On the other hand, serum glucocorticoid levels after the resident-intruder test were almost the same between the control and zinc-deficient mice. However, administration of Yokukansan to zinc-deficient mice significantly increased serum glucocorticoid level after the resident-intruder test and the significant difference in the rate of serum corticosterone level after the test to the basal level between the control and zinc-deficient mice was abolished. Dietary zinc deficiency increases the basal levels of serum glucocorticoid, while may insufficiently increase serum glucocorticoid levels in the resident-intruder test. The concentrations of glutamate and GABA (γ-aminobutyric acid) in the brain were significantly higher in zinc-deficient mice, while Yokukansan ameliorated the significant increases. These results indicate that Yokukansan ameliorates social isolation-induced aggressive behavior of zinc-deficient mice, probably via amelioration of abnormal glucocorticoid secretion. The ameliorative effect seems to be linked to the modification of glutamatergic neuron activity after administration of Yokukansan. 2010 Elsevier Inc. All rights reserved.

  3. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress

    OpenAIRE

    Shukitt-Hale, Barbara; Galli, Rachel L.; Meterko, Vanessa; Carey, Amanda; Bielinski, Donna F.; McGhie, Tony; Joseph, James A.

    2005-01-01

    Dietary supplementation with fruit or vegetable extracts can ameliorate age-related declines in measures of learning, memory, motor performance, and neuronal signal transduction in a rat model. To date, blueberries have proved most effective at improving measures of motor performance, spatial learning and memory, and neuronal functioning in old rats. In an effort to further characterize the bioactive properties of fruits rich in color and correspondingly high in anthocyanins and other polyphe...

  4. Potassium Bromate-induced Changes in the Adult Mouse Cerebellum Are Ameliorated by Vanillin.

    Science.gov (United States)

    Ben Saad, Hajer; Driss, Dorra; Jaballi, Imen; Ghozzi, Hanen; Boudawara, Ons; Droguet, Michael; Magné, Christian; Nasri, Monsef; Zeghal, Khaled Mounir; Hakim, Ahmed; Ben Amara, Ibtissem

    2018-02-01

    The current study aimed to elucidate the effect of vanillin on behavioral changes, oxidative stress, and histopathological changes induced by potassium bromate (KBrO3), an environmental pollutant, in the cerebellum of adult mice. The animals were divided into four groups: group 1 served as a control, group 2 received KBrO3, group 3 received KBrO3 and vanillin, and group 4 received only vanillin. We then measured behavioral changes, oxidative stress, and molecular and histological changes in the cerebellum. We observed significant behavioral changes in KBrO3-exposed mice. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. These effects were accompanied by decreased Na+-K+ and Mg2+ ATPase activity and antioxidant enzyme gene expression when compared to the control group. Additionally, there was a significant increase in cytokine gene expression in KBrO3-treated mice. Microscopy revealed that KBrO3 intoxication resulted in numerous degenerative changes in the cerebellum that were substantially ameliorated by vanillin supplementation. Co-administration of vanillin blocked the biochemical and molecular anomalies induced by KBrO3. Our results demonstrate that vanillin is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  5. Puerarin Ameliorates D-Galactose Induced Enhanced Hippocampal Neurogenesis and Tau Hyperphosphorylation in Rat Brain.

    Science.gov (United States)

    Hong, Xiao-Ping; Chen, Tao; Yin, Ni-Na; Han, Yong-Ming; Yuan, Fang; Duan, Yan-Jun; Shen, Feng; Zhang, Yan-Hong; Chen, Ze-Bin

    2016-01-01

    Enhanced neurogenesis has been reported in the hippocampus of patients with Alzheimer's disease (AD), the most common neurodegenerative disorder characterized with amyloid-β (Aβ) aggregation, tau hyperphosphorylation, and progressive neuronal loss. Previously we reported that tau phosphorylation played an essential role in adult hippocampal neurogenesis, and activation of glycogen synthase kinase (GSK-3), a crucial tau kinase, could induce increased hippocampal neurogenesis. In the present study, we found that treatment of D-galactose rats with Puerarin could significantly improve behavioral performance and ameliorate the enhanced neurogenesis and microtubule-associated protein tau hyperphosphorylation in the hippocampus of D-galactose rat brains. FGF-2/GSK-3 signaling pathway might be involved in the effects of Puerarin on hippocampal neurogenesis and tau hyperphosphorylation. Our finding provides primary in vivo evidence that Puerarin can attenuate AD-like enhanced hippocampal neurogenesis and tau hyperphosphorylation. Our finding also suggests Puerarin can be served as a treatment for age-related neurodegenerative disorders, such as AD.

  6. The Sulu-Sulawesi Sea: environmental and socioeconomic status, future prognosis and ameliorative policy options.

    Science.gov (United States)

    DeVantier, Lyndon; Alcala, Angel; Wilkinson, Clive

    2004-02-01

    The Sulu-Sulawesi Sea, with neighboring Indonesian Seas and South China Sea, lies at the center of the world's tropical marine biodiversity. Encircled by 3 populous, developing nations, the Philippines, Indonesia and Malaysia, the Sea and its adjacent coastal and terrestrial ecosystems, supports ca. 33 million people, most with subsistence livelihoods heavily reliant on its renewable natural resources. These resources are being impacted severely by rapid population growth (> 2% yr-1, with expected doubling by 2035) and widespread poverty, coupled with increasing international market demand and rapid technological changes, compounded by inefficiencies in governance and a lack of awareness and/or acceptance of some laws among local populations, particularly in parts of the Philippines and Indonesia. These key root causes all contribute to illegal practices and corruption, and are resulting in severe resource depletion and degradation of water catchments, river, lacustrine, estuarine, coastal, and marine ecosystems. The Sulu-Sulawesi Sea forms a major geopolitical focus, with porous borders, transmigration, separatist movements, piracy, and illegal fishing all contributing to environmental degradation, human suffering and political instability, and inhibiting strong trilateral support for interventions. This review analyzes these multifarious environmental and socioeconomic impacts and their root causes, provides a future prognosis of status by 2020, and recommends policy options aimed at amelioration through sustainable management and development.

  7. Mannose-binding lectin blunts macrophage polarization and ameliorates lupus nephritis.

    Directory of Open Access Journals (Sweden)

    Yanxing Cai

    Full Text Available BACKGROUND: Deficiency in clearance of self nuclear antigens, including DNA, is the hallmark of systemic lupus erythematosus (SLE, a chronic autoimmnue disease characterized by the production of various autoantibodies, immune complex deposition and severe organ damage. Our previous studies revealed that administration of syngeneic BALB/c mice with activated lymphocyte-derived DNA (ALD-DNA could induce SLE disease. Mannose-binding lectin (MBL, a secreted pattern recognition receptor with binding activity to DNA, has been proved to be a modulator of inflammation, but whether MBL takes responsibility for DNA clearance, modulates the DNA-mediated immune responses, and is involved in the development of DNA-induced SLE disease remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The levels of serum MBL significantly decreased in lupus mice induced by ALD-DNA and were negatively correlated with SLE disease. MBL blunted macrophage M2b polarization by inhibiting the MAPK and NF-κB signaling while enhancing the activation of CREB. Furthermore, MBL suppressed the ability of ALD-DNA-stimulated macrophages to polarize T cells toward Th1 cells and Th17 cells. Importantly, MBL supplement in vivo could ameliorate lupus nephritis. CONCLUSION/SIGNIFICANCE: These results suggest MBL supplement could alleviate SLE disease and might imply a potential therapeutic strategy for DNA-induced SLE, which would further our understanding of the protective role of MBL in SLE disease.

  8. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy.

    Science.gov (United States)

    Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul

    2010-03-01

    The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg. (c) Georg Thieme Verlag KG Stuttgart . New York.

  9. Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia.

    Science.gov (United States)

    Yin, Xue; Zhang, Xiuli; Lv, Changjun; Li, Chunli; Yu, Yan; Wang, Xiaozhi; Han, Fang

    2015-09-30

    Chronic intermittent hypoxia (CIH) is a serious consequence of obstructive sleep apnoea (OSA) and has deleterious effects on central neurons and neurocognitive functions. This study examined if protocatechuic acid (PCA) could improve learning and memory functions of rats exposed to CIH conditions and explore potential mechanisms. Neurocognitive functions were evaluated in male SD rats by step-through passive avoidance test and Morris water maze assay following exposure to CIH or room air conditions. Ultrastructure changes were investigated with transmission electron microscopy, and neuron apoptosis was confirmed by TUNEL assays. Ultrastructure changes were investigated with transmission electron microscope and neuron apoptosis was confirmed by TUNEL assays. The effects of PCA on oxidative stress, apoptosis, and brain IL-1β levels were investigated. Expression of Bcl-2, Bax, Cleaved Caspase-3, c-fos, SYN, BDNF and pro-BDNF were also studied along with JNK, P38 and ERK phosphorylation to elucidate the molecular mechanisms of PCA action. PCA was seen to enhance learning and memory ability, and alleviate oxidative stress, apoptosis and glial proliferation following CIH exposure in rats. In addition, PCA administration also decreased the level of IL-1β in brain and increased the expression of BDNF and SYN. We conclude that PCA administration will ameliorate CIH-induced cognitive dysfunctions.

  10. Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats.

    Science.gov (United States)

    Yassa, Hanan Dawood; Tohamy, Adel Fathy

    2014-06-01

    Medicinal plants attract growing interest in the therapeutic management of Diabetes mellitus. Moringa oleifera is a remarkably nutritious vegetable with several antioxidant properties. The present study assessed the possible antioxidant and antidiabetic effects of an aqueous extract of M. oleifera leaves in treating streptozotocin-induced diabetic albino rats. The antidiabetic effects of aqueous extract of M. oleifera leaves were assessed histomorphometrically, ultrastructurally and biochemically. Fasting plasma glucose (FPG) was monitored and morphometric measurements of β-cells of islets of Langerhans (modified Gomori's stain) and collagen fibers (Mallory's trichrome stain) were performed. The antioxidant effects of M. oleifera leaves were determined by measuring the reduced glutathione and lipid peroxidation product, malondialdehyde, in pancreatic tissue. M. oleifera treatment significantly ameliorated the altered FPG (from 380% to 145%), reduced glutathione (from 22% to 73%) and malondialdehyde (from 385% to 186%) compared to control levels. The histopathological damage of islet cells was also markedly reversed. Morphometrically, M. oleifera significantly increased the areas of positive purple modified Gomori stained β-cells (from 60% to 91%) and decreased the area percentage of collagen fibers (from 199% to 120%) compared to control values. Experimental findings clearly indicate the potential benefits of using the aqueous extract of M. oleifera leaves as a potent antidiabetic treatment. Copyright © 2014 Elsevier GmbH. All rights reserved.

  11. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets.

    Science.gov (United States)

    Lee, Yun Jung; Choi, Deok Ho; Cho, Guk Hyun; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-08-06

    Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD). EAL-I (100 mg·kg-1/day), EAL-II (200 mg·kg-1/day), and fluvastatin (3 mg·kg-1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.

  12. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    Directory of Open Access Journals (Sweden)

    Mohamed Naguib Zakaria

    2015-01-01

    Full Text Available Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE, AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS complications in STZ-induced (50 mg/kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze, neuronal degeneration (Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.

  13. The Ameliorating Effect of Myrrh on Scopolamine-Induced Memory Impairments in Mice

    Science.gov (United States)

    Baral, Samrat; Cho, Du-Hyong; Pariyar, Ramesh; Yoon, Chi-Su; Chang, Bo-yoon; Kim, Dae-Sung; Cho, Hyoung-Kwon; Kim, Sung Yeon; Kim, Youn-Chul; Kim, Jaehyo; Seo, Jungwon

    2015-01-01

    Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM) on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments. PMID:26635888

  14. Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats

    Science.gov (United States)

    Heo, Yu-Mi; Shin, Mal-Soon; Kim, Su-Hyun; Kim, Tae-Wook; Baek, Sang-Bin; Baek, Seung-Soo

    2014-01-01

    Alzheimer’s disease is the most common neurodegenerative disease and this disease induces progressive loss of memory function Scopolamine is a non-selective muscarinic cholinergic receptor antagonist and it induces impairment of learning ability. Exercise is known to ameliorate memory deficits induced by various brain diseases. In the present study, we investigated the effect of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus using the scopolamine-induced amnesia mice. For the induction of amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once a day for 14 days. Morris water maze test for spatial learning ability was conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) were performed. In the present results, scopolamine-induced amnesia mice showed deterioration of spatial learning ability. Inhibition of cell proliferation and suppression of BDNF and TrkB expressions were observed in the scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning ability and increased cell proliferation through activating of BDNF-TrkB pathway in the amnesia mice. These findings offer a possibility that treadmill exercise may provide preventive or therapeutic value for the memory loss induced by variable neurodegenerative diseases including Alzheimer’s disease. PMID:25061594

  15. A lactic acid bacterium isolated from kimchi ameliorates intestinal inflammation in DSS-induced colitis.

    Science.gov (United States)

    Park, Jin-Soo; Joe, Inseong; Rhee, Paul Dong; Jeong, Choon-Soo; Jeong, Gajin

    2017-04-01

    Some species of lactic acid bacteria have been shown to be beneficial in inflammatory bowel disease (IBD). In the present study, a strain of lactic acid bacterium (Lactobacillus paracasei LS2) was isolated from the Korean food, kimchi, and was shown to inhibit the development of experimental colitis induced by dextran sulfate sodium (DSS). To investigate the role of LS2 in IBD, mice were fed DSS in drinking water for seven days along with LS2 bacteria which were administered intragastrically to some of the mice, while phosphate-buffered saline (PBS) was administered to others (the controls). The administration of LS2 reduced body weight loss and increased survival, and disease activity indexes (DAI) and histological scores indicated that the severity of colitis was significantly reduced. The production of inflammatory cytokines and myeloperoxidase (MPO) activity also decreased. Flow cytometry analysis showed that the number of Th1 (IFN-γ) population cells was significantly reduced in the LS2-administered mice compared with the controls. The administration of LS2 induced the increase of CD4 + FOXP3 + Treg cells, which are responsible for IL-10. Numbers of macrophages (CD11b + F4/80 + ), and neutrophils (CD11b + Gr-1 + ) among lamina propria lymphocytes (LPL) were also reduced. These results indicate that LS2 has an anti-inflammatory effect and ameliorates DSS-induced colitis.

  16. Kalpaamruthaa ameliorates mitochondrial and metabolic alterations in diabetes mellitus induced cardiovascular damage.

    Science.gov (United States)

    Latha, Raja; Shanthi, Palanivelu; Sachdanandam, Panchanadham

    2014-12-01

    Efficacy of Kalpaamruthaa on the activities of lipid and carbohydrate metabolic enzymes, electron transport chain complexes and mitochondrial ATPases were studied in heart and liver of experimental rats. Cardiovascular damage (CVD) was developed in 8 weeks after type 2 diabetes mellitus induction with high fat diet (2 weeks) and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 hr interval). In CVD-induced rats, the activities of total lipase, cholesterol ester hydrolase and cholesterol ester synthetase were increased, while lipoprotein lipase and lecithin-cholesterol acyltransferase activities were decreased. The activities of lipid-metabolizing enzymes were altered by Kalpaamruthaa in CVD-induced rats towards normal. Kalpaamruthaa modulated the activities of glycolytic enzymes (hexokinase, phosphogluco-isomerase, aldolase and glucose-6-phosphate dehydrogenase), gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) and glycogenolytic enzyme (glycogen phosphorylase) along with increased glycogen content in the liver of CVD-induced rats. The activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, α-ketoglutarate dehydrogenase, Complexes and ATPases (Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) were decreased in CVD-induced rats, which were ameliorated by the treatment with Kalpaamruthaa. This study ascertained the efficacy of Kalpaamruthaa for the treatment of CVD in diabetes through the modulation of metabolizing enzymes and mitochondrial dysfunction.

  17. Searching for a placental derived ES-62-like molecule to explain rheumatoid arthritis amelioration in pregnancy

    Directory of Open Access Journals (Sweden)

    Craig D. Scoville

    2014-11-01

    Full Text Available The majority of women with rheumatoid arthritis (RA experience disease amelioration during pregnancy for unclear reasons. One possible explanation pursued and described here is whether the placenta produces a protein similar to the immunomodulating protein, ES-62, excreted by filarial nematodes. This protein has also been shown to reduce disease activity in animal models of RA. Eleven human placentas were prepared and a polyclonal anti-ES-62 antiserum was used to identify if any ES-62-like molecule exists from human placental tissues. Any bands identified were then excised from the gel and sent for mass spectrometry and protein identification. The anti-serum showed consistent cross reactivity with the heavy chain from immunoglobulin G (IgG from the eleven human placentas by mass spectrometry. No primary sequence homology between the heavy chain of IgG and ES-62 was identified. The placenta does not produce an ES-62-like molecule. However the binding of the antiserum to the Fc region of IgG suggests that this may be a possible mechanism for rheumatoid factor production in some patients with chronic filarial infections.

  18. Fungal phytases: characteristics and amelioration of nutritional quality and growth of non-ruminants.

    Science.gov (United States)

    Singh, B; Satyanarayana, T

    2015-08-01

    Fungal phytases are histidine acid phosphatases, a subclass of acid phosphatases, which catalyse the hydrolysis of phytic acid resulting in the release of phosphate moieties and thus mitigate its antinutritional properties. The supplementation of feed with phytases increases the bioavailability of phosphorus and minerals in non-ruminant animals and reduces the phosphorus pollution due to phosphorus excretion in the areas of intensive livestock production. Although phytases are reported in plants, animals and micro-organisms, fungal sources are used extensively for the production of phytases on a commercial scale. Phytases have been produced by fungi in both solid-state fermentation (SSF) and submerged fermentation (SmF). The fungal phytases are high molecular weight proteins ranging from 35 to 500 kDa. They are optimally active within pH and temperature ranges between 4.5 and 6.0, and 45 and 70 °C respectively. Phytate degradation leads to amelioration in the nutritional status of foods and feeds by improving the availability of minerals, phosphorus and proteins in non-ruminant animals and human beings and thus mitigates the environmental phosphorus pollution. Our article focuses on the role of fungal phytases in improving nutritional value of foods and feeds with concomitant increase in growth of non-ruminant animals and mitigating environmental phosphorus pollution. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  19. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets

    Directory of Open Access Journals (Sweden)

    Lee Yun

    2012-08-01

    Full Text Available Abstract Background Arctium lappa L. (Asteraceae, burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD. Method EAL-I (100 mg·kg−1/day, EAL-II (200 mg·kg−1/day, and fluvastatin (3 mg·kg−1/day groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Results Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM-1, vascular cell adhesion molecule (VCAM-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. Conclusion The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.

  20. Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations.

    Science.gov (United States)

    Vasant, Rupal A; Narasimhacharya, A V R L

    2012-11-01

    Fluoride is a serious health hazard across several nations, and chronic intake of fluoride deranges the carbohydrate, lipid and antioxidant metabolism in general. As there are limited remedial measures to prevent fluorosis, we investigated the role of tamarind leaf as a food supplement in restoration of carbohydrate, lipid and antioxidant metabolism in fluoride-exposed albino rats. Albino rats were exposed to fluoride (100 ppm sodium fluoride) through drinking water and fed diet supplemented with tamarind leaf powder (2.5, 5 and 10 g %) for 4 weeks. Carbohydrate, lipid and antioxidant profiles were investigated in both controls and fluoride-exposed animals. While 4-week exposure to fluoride elevated plasma glucose and lipid profiles, simulating diabetic and hyperlipidaemic conditions, the antioxidant defence mechanisms of fluoride-exposed rats were compromised, with elevation and decline in lipid peroxidation and high-density lipoprotein (HDL)-cholesterol, respectively. When the diet was supplemented with tender tamarind leaves (used in southern India as a replacement for tamarind or other sour food ingredients), significant improvements in carbohydrate and lipid profiles occurred as evidenced by decreased plasma glucose and lipid levels, lipid peroxidation, increased hepatic glycogen content, hexokinase activity and cholesterol excretion, with simultaneous improvement in antioxidant profiles of both hepatic and renal tissues. These findings are significant in view of the need for cost-effective approaches to tackle fluorosis as an environmental hazard and use of food supplements as ameliorative measures.

  1. Sesamin Ameliorates Advanced Glycation End Products-Induced Pancreatic β-Cell Dysfunction and Apoptosis

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2015-06-01

    Full Text Available Advanced glycation end products (AGEs, the direct modulators of β-cells, have been shown to cause insulin-producing β-cell dysfunction and apoptosis through increase of intracellular reactive oxygen species (ROS production. Sesamin has been demonstrated to possess antioxidative activity. This study was designed to investigate whether sesamin protects against AGEs-evoked β-cell damage via its antioxidant property. The effects of sesamin were examined in C57BL/6J mice and MIN6 cell line. In in vivo studies, mice were intraperitoneally injected with AGEs (120 mg/kg and orally treated with sesamin (160 mg/kg for four weeks. Intraperitoneal glucose tolerance and insulin releasing tests were performed. Insulin content, ROS generation and β-cell apoptosis in pancreatic islets were also measured. In in vitro studies, MIN6 cells were pretreated with sesamin (50 or 100 μM and then exposed to AGEs (200 mg/L for 24 h. Insulin secretion, β-cell death, ROS production as well as expression and activity of NADPH oxidase were determined. Sesamin treatment obviously ameliorated AGE-induced β-cell dysfunction and apoptosis both in vivo and in vitro. These effects were associated with decreased ROS production, down-regulated expression of p67phox and p22phox, and reduced NADPH oxidase activity. These results suggest that sesamin protects β-cells from damage caused by AGEs through suppressing NADPH oxidase-mediated oxidative stress.

  2. Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid metabolism in the streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ren, Tingyuan; Zhu, Yuping; Kan, Jianquan

    2017-01-01

    This study aimed to evaluate the effects of Zanthoxylum alkylamides on the glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes. Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides for 28 days. Alkylamides significantly decreased fasting blood glucose and fructosamine content, as well as relieved organ enlargement caused by diabetes. The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents of rats with STZ-induced diabetes were significantly reduced. Total cholesterol in the liver also significantly decreased. Quantitative polymerase chain reaction (Q-PCR) and Western blot detected insignificantly increased (P > 0.05) mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK) in the skeletal muscle of diabetic rats. However, AMPK and p-AMPK (Thr172) protein expression levels significantly increased. The mRNA and protein expression levels of silencing information regulator 1 significantly increased. The mRNA expression levels of acetyl-CoA-carboxylase (ACC) and protein p-ACC (Ser79) also increased. The mRNA and protein expression levels of glucose transporter type 4 (GLUT4) were significantly upregulated in the skeletal muscle cell membranes of diabetic rats. Results indicated that alkylamides activated the AMPK-signaling pathway. Thus, inhibiting ACC activity reduced fatty-acid synthesis. The rapid translocation of GLUT4 mediated increased glucose transport rate and reduced blood glucose. Therefore, alkylamides can ameliorate glucose and lipid metabolism disorders in diabetic rats by activating the AMPK pathway.

  3. Enhanced interannual precipitation variability increases plant functional diversity that in turn ameliorates negative impact on productivity.

    Science.gov (United States)

    Gherardi, Laureano A; Sala, Osvaldo E

    2015-12-01

    Although precipitation interannual variability is projected to increase due to climate change, effects of changes in precipitation variance have received considerable less attention than effects of changes in the mean state of climate. Interannual precipitation variability effects on functional diversity and its consequences for ecosystem functioning are assessed here using a 6-year rainfall manipulation experiment. Five precipitation treatments were switched annually resulting in increased levels of precipitation variability while maintaining average precipitation constant. Functional diversity showed a positive response to increased variability due to increased evenness. Dominant grasses decreased and rare plant functional types increased in abundance because grasses showed a hump-shaped response to precipitation with a maximum around modal precipitation, whereas rare species peaked at high precipitation values. Increased functional diversity ameliorated negative effects of precipitation variability on primary production. Rare species buffered the effect of precipitation variability on the variability in total productivity because their variance decreases with increasing precipitation variance. © 2015 John Wiley & Sons Ltd/CNRS.

  4. Amelioration of some biochemical parameters in irradiated male albino rats by garlic

    International Nuclear Information System (INIS)

    El-masry, F.S.H.; El-sayed, N.M.; Hussein, A.H.

    2005-01-01

    Garlic extract has various medical effects on the treatment of many diseases as hypertension, atherosclerosis, inflammation and diabetes. The alteration of the biochemical parameters in blood serum of irradiated rats may play an important role in determining the pathogenesis of radiation exposure. Many of the damaging effects of ionizing radiation are mediated by reactive free radicals. This study was designed to evaluate the protective role of garlic against gamma irradiation (5Gy) induced biochemical disorders in rats. Samples were collected at 1, 7 and 14 days post-irradiation. Lipid peroxide content (malondialdehyde), cholesterol, HDL-C, LDL-C, fatty acids, glucose, insulin, glycogen, haemoglobin, ferritin andiron were estimated.Garlic was orally administered to rats (100 mg/kg body weight) for 14 days before exposure to single dose of gamma irradiation at dose level 5 Gy. The data revealed significant increase in the levels of lipid peroxide, cholesterol, LDL-cholesterol, fatty acids, insulin, glucose and iron accompanied with significant decrease in the levels of HDL-cholesterol, glycogen, haemoglobin and ferritin due to radiation exposure. Administration of garlic alone to the rats caused nonsignificant changes in the estimated parameters indicating its safe use, but the treatment with garlic to rats before radiation exposure ameliorated the changes induced by gamma irradiation and tended to normalize their levels.It could be concluded that garlic administration may has a beneficial role in restoring the biochemical disorders induced by 5 Gy gamma irradiation

  5. Amelioration of radiation induced oxidative stress using water soluble chitosan produced by Aspergillus niger

    International Nuclear Information System (INIS)

    EL-Sonbaty, S.M.; Swailam, H.M.; Noaman, E.

    2012-01-01

    Chitosan is a natural polysaccharide synthesized by a great number of living organisms and considered as a source of potential bioactive material and has many biological applications which are greatly affected by its solubility in neutral ph. In this study low molecular weight water soluble chitosan was prepared by chemical degradation of chitosan produced by Aspergillus niger using H 2 O 2 . Chitosan chemical structure was detected before and after treatment using FTIR spectrum, and its molecular weight was determined by its viscosity using viscometer. Its antioxidant activity against gamma radiation was evaluated in vivo using rats. Rats were divided into 4 groups; group 1: control, group 2: exposed to acute dose of gamma radiation (6 Gy), group 3: received water soluble chitosan, group 4: received water soluble chitosan then exposed to gamma radiation as group 2. Gamma radiation significantly increased malonaldehyde, decreased glutathione concentration, activity of superoxide dismutase, catalase, and glutatione peroxidase, while significantly increase the activity of alanine transferase, aspartate transferase, urea and creatinine concentration. Administration of water soluble chitosan has ameliorated induced changes caused by gamma radiation. It could be concluded that water soluble chitosan by scavenging free radicals directly or indirectly may act as a potent radioprotector against ionizing irradiation.

  6. Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Ibrahim, Marwa A; Khalaf, A A; Galal, Mona K; Ogaly, Hanan A; H M Hassan, Azza

    2015-12-01

    The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

  7. Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.

    Science.gov (United States)

    Wijayawardhane, Nayana; Shonesy, Brian C; Vaithianathan, Thirumalini; Pandiella, Noemi; Vaglenova, Julia; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu

    2008-01-01

    Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.

  8. Treadmill exercise ameliorates social isolation-induced depression through neuronal generation in rat pups.

    Science.gov (United States)

    Cho, Jung-Wan; Jung, Sun-Young; Lee, Sang-Won; Lee, Sam-Jun; Seo, Tae-Beom; Kim, Young-Pyo; Kim, Dae-Young

    2017-12-01

    Social isolation is known to induce emotional and behavioral changes in animals and humans. The effect of treadmill exercise on depression was investigated using social isolated rat pups. The rat pups in the social isolation groups were housed individually. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. In order to evaluate depression state of rat pups, forced swimming test was performed. Newly generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. We examined the expression of 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe using immunofluorescence. The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was detected by Western blot analysis. The present results demonstrated that social isolation increased resting time and decreased mobility time. Expression of 5-HT and TPH in the dorsal raphe and expression of BDNF and TrkB in the hippocampus were decreased by social isolation. The number of BrdU-positive cells in the hippocampal dentate gyrus was suppressed by social isolation. Treadmill exercise decreased resting time and increased mobility in the social isolated rat pups. Expression of 5-HT, TPH, BDNF, and TrkB was increased by treadmill exercise. The present results suggested that treadmill exercise may ameliorates social isolation-induced depression through increasing neuronal generation.

  9. Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats.

    Science.gov (United States)

    Zhao, Zi-Wen; Cai, Wei; Lin, Yun-Ling; Lin, Qing-Fei; Jiang, Qiong; Lin, Zhang; Chen, Liang-Long

    2011-01-01

    The present study was designed to examine whether astaxanthin (ASX, 3,3-dihydroxybeta, beta-carotene-4,4-dione, CAS 472-61-7), a dietary antioxidant carotenoid that is naturally present in algae, crustaceans, and fish, has a protective effect on endothelial dysfunction of aortas in diabetic rats and the possible molecular mechanism involved. Male Wistar rats were randomly divided into four groups: control rats, diabetic rats, diabetic rats treated with ASX (10 mg/kg/d), and control rats treated with ASX. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/ kg). STZ-induced diabetes in rats was complicated with excessive oxidative stress and endothelial dysfunction, increased serum oxidized low-density lipoprotein (ox-LDL) and aortic malondialdehyde (MDA) levels, inhibited endothelium-dependent vasorelaxation to acetylcholine (ACh) and unaffected endothelium-dependent vasorelaxation to sodium nitroprusside (SNP). Simultaneously, lectin-like oxLDL receptor-i (LOX-1) expression was enhanced and endothelial nitric oxide (NO) synthase (eNOS) expression was reduced in the aortas of diabetic rats. ASX treatment could significantly decrease serum oxLDL and aortic MDA levels, attenuate blunted endothelium-dependent vasodilator responses to ACh, upregulate eNOS expression, and decrease LOX-1 expression. These results indicated that ASX could ameliorate diabetic endothelial dysfunction by inhibiting the ox-LDLLOX-1-eNOS pathway. Treatment with ASX might be clinically useful for diabetic complications associated with endothelial dysfunction.

  10. Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice

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    Mohamed A Dkhi

    2014-01-01

    Full Text Available BACKGROUND: Schistosomiasis is caused by helminth parasites of the genus Schistosoma. Berberine chloride (BER, an isoquinoline alkaloid, has been used in vivo for its antiparasitic, antioxidant and hepatoprotective properties. In this study, the protective effect of BER and praziquantel has been compared for the extent of schistosomiasis-induced oxidative stress in hepatic tissue of mice. RESULTS: S. mansoni was able to induce inflammation and injury to the liver, evidenced (i by an increase in inflammatory cellular infiltrations, dilated sinusoids and vacuolated hepatocytes, (ii by decreased levels of alanine and aspartate aminotransferases and increased levels of alkaline phosphatase, γ-glutamyl transferase in the liver homogenate, (iii by increased production of nitric oxide and thiobarbituric acid reactive substances, and (iv by lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly altered during BER treatment. In particular, berberine counteracted the S. mansoni-induced loss of glutathione and the activities of catalase and superoxide dismutase. CONCLUSION: Based on these results, it is concluded that berberine could ameliorate pre-existing liver damage and oxidative stress conditions due to schistosomiasis.

  11. Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

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    Tatsuya eKobayashi

    2015-02-01

    Full Text Available Sexual behavior is suppressed by various types of stressors. We previously demonstrated that an alarm pheromone released by stressed male Wistar rats is a stressor to other rats, increases the number of mounts needed for ejaculation, and decreases the hit rate (described as the number of intromissions/sum of the mounts and intromissions. This deterioration in sexual behavior was ameliorated by pretreatment with the opioid receptor antagonist naloxone. However, the neural mechanism underlying this remains to be elucidated. Here, we examined Fos expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the alarm pheromone increased the number of mounts and decreased the hit rate. In addition, Fos expression was increases in the anterior medial division, anterior lateral division and posterior division of the bed nucleus of the stria terminalis, parvocellular part of the paraventricular nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Fos expression decreased in the magnocellular part of the paraventricular nucleus of the hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in Fos expression in the magnocellular part of the paraventricular nucleus of the hypothalamus, ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Based on these results, we hypothesize that the alarm pheromone deteriorated sexual behavior by activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis cluster and suppressing the magnocellular part of the paraventricular nucleus of the hypothalamus via the opioidergic pathway.

  12. Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin

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    Abderrahim Nemmar

    2015-07-01

    Full Text Available Background/Aim: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6-methylanthraquinone, which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. Methods: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg or saline (control. Emodin (4 mg/kg was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Results: Emodin significantly prevented the increase of leukocyte (n=8, Pin vivo prothrombotic effect of DEP in pial arterioles (n=6, Pin vitro in whole blood (n=4-5, PConclusion: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution.

  13. The Ameliorating Effect of Myrrh on Scopolamine-Induced Memory Impairments in Mice

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    Samrat Baral

    2015-01-01

    Full Text Available Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK. Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments.

  14. Role of hydrotherapy in the amelioration of oxidant-antioxidant status in rheumatoid arthritis patients.

    Science.gov (United States)

    Mateen, Somaiya; Moin, Shagufta; Khan, Abdul Q; Zafar, Atif; Fatima, Naureen; Shahzad, Sumayya

    2017-06-14

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Reactive oxygen species (ROS) are involved in the pathophysiology of RA. Moderate intensity exercises have been reported to have anti-oxidant and anti-inflammatory effects. The aim of this study was to evaluate the effect of hydrotherapy on oxidant-antioxidant status in RA patients. Forty RA patients and 30 age- and sex-matched healthy controls were included in this study. RA patients were subdivided into two groups: the first group (n = 20) received treatment with conventional RA drugs, while the second group (n = 20) received hydrotherapy along with the conventional drugs for a period of 12 weeks. Disease Activity Score of 28 joints (DAS-28), ROS level, protein oxidation, lipid peroxidation, DNA damage and the activities of antioxidant enzymes were evaluated before and after 12 weeks of treatment. RA patients showed a significant change in the oxidative stress biomarkers (ROS, P hydrotherapy has decreased protein, lipid and DNA oxidation by increasing the activities of antioxidant enzymes (SOD and GPx). Our results indicate that hydrotherapy along with drugs has reduced the severity of disease (DAS-28) by ameliorating the oxidant-antioxidant status in RA patients. Thus, in addition to conventional drugs, RA patients should be advised to have hydrotherapy (moderate intensity exercise) in their treatment regimen. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  15. Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

    Science.gov (United States)

    Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

    2018-01-01

    The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

  16. Delivery of Placenta-Derived Mesenchymal Stem Cells Ameliorates Ischemia Induced Limb Injury by Immunomodulation

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    Bo Zhang

    2014-11-01

    Full Text Available Background: Peripheral artery disease (PAD is a major health burden in the world. Stem cell-based therapy has emerged as an attractive treatment option in regenerative medicine. In this study, we sought to test the hypothesis that stem cell-based therapy can ameliorate ischemia induced limb injury. Methods: We isolated mesenchymal stem cells derived from human placentas (PMSCs and intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs reduced acute muscle fibers apoptosis induced by ischemia. Results: PMSC treatment significantly enhanced regeneration of the injured hind limb by reducing fibrosis and enhancing running capacity when the animals were subjected to treadmill training. Mechanistically, injected PMSCs can modulate acute inflammatory responses by reducing neutrophil and macrophage infiltration following limb ischemia. ELISA assays further confirmed that PMSC treatment can also reduce pro-inflammatory cytokines, TNF-α and IL-6, and enhance anti-inflammatory cytokine, IL-10 at the injury sites. Conclusion: Taken together, our results demonstrated that PMSCs can be a potential effective therapy for treatment of PAD via immunomodulation.

  17. Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats.

    Science.gov (United States)

    Heo, Yu-Mi; Shin, Mal-Soon; Kim, Su-Hyun; Kim, Tae-Wook; Baek, Sang-Bin; Baek, Seung-Soo

    2014-06-01

    Alzheimer's disease is the most common neurodegenerative disease and this disease induces progressive loss of memory function Scopolamine is a non-selective muscarinic cholinergic receptor antagonist and it induces impairment of learning ability. Exercise is known to ameliorate memory deficits induced by various brain diseases. In the present study, we investigated the effect of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus using the scopolamine-induced amnesia mice. For the induction of amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once a day for 14 days. Morris water maze test for spatial learning ability was conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) were performed. In the present results, scopolamine-induced amnesia mice showed deterioration of spatial learning ability. Inhibition of cell proliferation and suppression of BDNF and TrkB expressions were observed in the scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning ability and increased cell proliferation through activating of BDNF-TrkB pathway in the amnesia mice. These findings offer a possibility that treadmill exercise may provide preventive or therapeutic value for the memory loss induced by variable neurodegenerative diseases including Alzheimer's disease.

  18. Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence.

    Science.gov (United States)

    Sachdeva, Anand Kamal; Kuhad, Anurag; Tiwari, Vinod; Chopra, Kanwaljit

    2009-12-28

    Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

  19. Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection

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    Yu-Cheng Li

    2016-10-01

    Full Text Available Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg, fluoxetine (20 mg/kg and pioglitazone (10 mg/kg were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.

  20. Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.

    Science.gov (United States)

    Suresh Babu, P; Srinivasan, K

    1998-04-01

    Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels.

  1. Treatment with antioxidants ameliorates oxidative damage in a mouse model of propionic acidemia.

    Science.gov (United States)

    Rivera-Barahona, Ana; Alonso-Barroso, Esmeralda; Pérez, Belén; Murphy, Michael P; Richard, Eva; Desviat, Lourdes R

    2017-09-01

    Oxidative stress contributes to the pathogenesis of propionic acidemia (PA), a life threatening disease caused by the deficiency of propionyl CoA-carboxylase, in the catabolic pathway of branched-chain amino acids, odd-number chain fatty acids and cholesterol. Patients develop multisystemic complications including seizures, extrapyramidal symptoms, basal ganglia deterioration, pancreatitis and cardiomyopathy. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species and oxidative damage, all of which have been documented in patients' samples and in a hypomorphic mouse model. Here we set out to investigate whether treatment with a mitochondria-targeted antioxidant, MitoQ, or with the natural polyphenol resveratrol, which is reported to have antioxidant and mitochondrial activation properties, could ameliorate the altered redox status and its functional consequences in the PA mouse model. The results show that oral treatment with MitoQ or resveratrol decreases lipid peroxidation and the expression levels of DNA repair enzyme OGG1 in PA mouse liver, as well as inducing tissue-specific changes in the expression of antioxidant enzymes. Notably, treatment decreased the cardiac hypertrophy marker BNP that is found upregulated in the PA mouse heart. Overall, the results provide in vivo evidence to justify more in depth investigations of antioxidants as adjuvant therapy in PA. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

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    Guang-xing Shui

    2017-01-01

    Full Text Available Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD on chronic aristolochic acid nephropathy (AAN in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN, the saline-treated group (AAN + vehicle, the normal dose DFD-treated group (AAN + NDFD, the high dose DFD-treated group (AAN + HDFD, and the rosiglitazone treated group (AAN + Rosi. After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA, mitochondrial membrane potential (MMP, ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

  3. Ameliorative effect of ethyl pyruvate in neuropathic pain induced by chronic constriction injury of sciatic nerve

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    Varsha J. Bansode

    2014-01-01

    Full Text Available Objective: The present study was designed to investigate the ameliorative effects of ethyl pyruvate (EP in chronic constriction injury (CCI-induced painful neuropathy in rats. Materials and Methods: EP 50 and 100 mg/kg was administered for 21 consecutive days starting from the day of surgery. The effects of EP in the paw pressure, acetone drop, and tail heat immersion tests were assessed, reflecting the degree of mechanical hyperalgesia, cold allodynia, and spinal thermal sensation, respectively. Axonal degeneration of the sciatic nerve was assessed histopathologically. The levels of thiobarbituric acid reactive species, reduced glutathione (GSH, catalase (CAT, and superoxide dismutase (SOD were determined to assess oxidative stress. Key Findings: Administration of 50 and 100 mg/kg EP attenuated the reduction of nociceptive threshold in the paw pressure, acetone drop, and tail heat immersion tests. EP 100 mg/kg significantly attenuated reactive changes in histopathology and increase in oxidative stress. Conclusion: EP 100 mg/kg showed beneficial activity against nerve trauma-induced neuropathy. Hence, it can be used as a better treatment option in neuropathic pain (NP. The observed antinociceptive effects of EP may possibly be attributed to its antioxidant and anti-inflammatory activity.

  4. Use of Some Methods for Amelioration Heat Stress in Friesian Calves

    International Nuclear Information System (INIS)

    Aboulnaga, A.I.; Kamal, T.H.

    2008-01-01

    Twenty Friesian calves of 3-4 months of age and 90 kg average body weight, were used to investigate the effect of hot climate (36 degree C, 65% R.H.) and evaluate two methods of ameliorating heat stress, the first method was feed supplementation with urea and mineral mixture and the second was water sprinkling and supplying the heat stressed animals with cool water. Daily body gain (DBG) was calculated, while serum protein, urea N, cholesterol, creatine, alkaline phosphatase (Alk-P) and acid phosphatase (Ac-P) were determined in this study. The first and second treatments were carried out inside the climatic chamber and the third was undertaken outdoors (36.5± 2.5 degree C, 62.5±4.5% R.H.). Heat stress induced a significant decrease in DBG, serum protein, urea N, cholesterol, creatine and plasma aldosterone (P<0.01) and serum Alk-P (P<0.05), while the serum Ac-P decreased insignificantly. The nutritional treatment caused a significant increase in DBG serum protein And urea N (P<0.01) and serum creatine (P<0.05). Sprinkling and drinking cooled water caused an increase in serum cholesterol, plasma aldosterone (P<0.01), DBG, serum protein and creatine (P<0.05)

  5. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

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    Joo Wan Kim

    2015-01-01

    Full Text Available The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF on sciatic neurectomy- (NTX- induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation.

  6. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant Extract

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    Priyanka Sharma

    2011-01-01

    Full Text Available The primary objective of this investigation is to determine the deleterious effects of sub lethal gamma radiation on testes and their possible inhibition by Tinospora cordifolia extract (TCE. For this purpose, one group of male Swiss albino mice was exposed to 7.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day orally for 5 consecutive days half an hr before irradiation to serve as experimental. Exposure of animals to 7.5 Gy gamma radiation resulted into significant decrease in body weight, tissue weight, testes- body weight ratio and tubular diameter up to 15 days of irradiation. Cent percent mortality was recorded by day 17th in irradiated control, whereas all animals survived in experimental group. TCE pretreatment rendered significant increase in body weight, tissue weight, testes- body weight ratio and tubular diameter at various intervals as compared to irradiated group. Radiation induced histological lesions in testicular architecture were observed more severe in irradiated control then the experimental. TCE administration before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio- protective potential of Tinospora cordifolia root extract in testicular constituents against gamma irradiation in mice.

  7. Factors which deter potential science/math teachers from teaching; changes necessary to ameliorate their concerns

    Science.gov (United States)

    Evans, Robert H.

    In light of the perceived national need for more science and math teachers, this study was conceived to:1.Identify teaching oriented students among freshmen at a mid-western engineering school, who have chosen NOT to become teachers;2.Find out what reasons these potential science and math teachers have for deciding not to pursue teaching careers;3.Determine what amelioration of these problems would be necessary for them to no longer be factors which would inhibit students from becoming teachers.Of a random sample of 110 students drawn from a freshman class, 98 participated fully in the study. Each participant took Holland's Self-Directed Search to determine teaching orientation and author-constructed instruments to assess their concerns about teaching.Results showed teaching oriented students avoided teaching due to low starting salaries, lack of job security, low maximum salaries, not wanting to do the work teacher's do, poor job availability and discouragement by family and friends. Starting salaries of 21,693 and salaries of 32,600 for a teacher with a B.A. and 10 years experience were among the changes deemed necessary to make teaching attractive.

  8. The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease.

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    Sabine Westphal

    Full Text Available Allogeneic hematopoetic stem cell transplantation (allo-HSCT is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD, a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG, a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.

  9. Low Doses of Simvastatin Therapy Ameliorate Cardiac Inflammatory Remodeling in Trypanosoma cruzi-Infected Dogs

    Science.gov (United States)

    Melo, Lilian; Caldas, Ivo Santana; Azevedo, Maíra Araújo; Gonçalves, Karolina Ribeiro; da Silva do Nascimento, Alvaro Fernando; Figueiredo, Vivian Paulino; de Figueiredo Diniz, Lívia; de Lima, Wanderson Geraldo; Torres, Rosália Moraes; Bahia, Maria Terezinha; Talvani, André

    2011-01-01

    Chagas cardiomyopathy remodeling is based on the presence of Trypanosoma cruzi in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of T. cruzi. Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with T. cruzi-induced ventricular dysfunctions. PMID:21292909

  10. Natural Antioxidant-Isoliquiritigenin Ameliorates Contractile Dysfunction of Hypoxic Cardiomyocytes via AMPK Signaling Pathway

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    Xiaoyu Zhang

    2013-01-01

    Full Text Available Isoliquiritigenin (ISL, a simple chalcone-type flavonoid, is derived from licorice compounds and is mainly present in foods, beverages, and tobacco. Reactive oxygen species (ROS is a critical factor involved in modulating cardiac stress response signaling during ischemia and reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via modulating cellular redox status and regulating cardioprotective signaling pathways. The fluorescent probe H2DCFDA was used to measure the level of intracellular ROS. The glucose uptake was determined by 2-deoxy-D-glucose-3H accumulation. The IonOptix System measured the contractile function of isolated cardiomyocytes. The results demonstrated that ISL treatment markedly ameliorated cardiomyocytes contractile dysfunction caused by hypoxia. ISL significantly stimulated cardioprotective signaling, AMP-activated protein kinase (AMPK, and extracellular signal-regulated kinase (ERK signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL significantly reduced cardiac ROS level during hypoxia/reoxygenation. Moreover, ISL reduced the mitochondrial potential (Δψ of isolated mouse cardiomyocytes. Taken together, ISL as a natural antioxidant demonstrated the cardioprotection against ischemic injury that may attribute to the activation of AMPK and ERK signaling pathways and balance of cellular redox status.

  11. Ameliorating effect of vitamin E on in vitro development of preimplantation buffalo embryos.

    Science.gov (United States)

    Thiyagarajan, B; Valivittan, K

    2009-04-01

    Oxidative stress has been implicated in the etiology of defective embryo development. Vitamin E is an effective lipid-soluble antioxidant, protecting cell membranes from peroxidative damage. In this context, this study was undertaken to find if supplementation of vitamin E in culture medium could ameliorate the developmental competence of preimplantation buffalo embryos. Vitamin E was supplemented in maturation/embryo culture medium at concentrations of 0, 50, 100, 200 and 400 microM. The developmental competence of buffalo embryos was assessed by observing the cleavage, morulae, blastocyst rate, total cell count and comet assay. Vitamin E had no significant effect in maturation medium. Vitamin E in embryo culture medium under 5% O(2) significantly reduced blastocyst formation in the 400 microM supplemented group. Culture under 20% O(2) enhanced the frequency of blastocyst formation, total cell count and significantly reduced comet tail in the 100 microM supplemented group (P Vitamin E in ECM for the first 72 h of culture period enhanced blastocyst rate and total cell number in the 100 microM group (P Vitamin E may enhance the developmental competence of buffalo embryos in vitro by protecting them from oxidative stress.

  12. Domperidone can ameliorate deleterious reproductive effects and reduced weight gain associated with fescue toxicosis in heifers.

    Science.gov (United States)

    Jones, K L; King, S S; Griswold, K E; Cazac, D; Cross, D L

    2003-10-01

    The aim of this study was to evaluate the effect of a dopamine antagonist, domperidone, in nonpregnant, reproductively cycling heifers consuming endophyte-infected (EI) fescue diets. Thirty crossbred heifers (Angus x Holstein or Hereford x Holstein) were assigned to one of three treatment groups (n = 10); endophyte-free (EF) fescue diet, EI fescue diet, or endophyte-infected diet and treated with domperidone (EID). Heifers fed EI diets had decreased weight gains compared with heifers fed EF or EID (P daily and analyzed for progesterone concentration to determine luteal function. Heifers ingesting EI diets had estrous cycles of shorter duration and lower mid-cycle progesterone concentrations than heifers in the EF or EID treatments (P heifers in each group (n = 3 per group) were harvested and in vitro secretion of progesterone from luteal tissue extracts was determined. No differences in progesterone concentrations were detected among luteal tissue incubates (P > 0.05). These results suggest that domperidone supplementation of heifers consuming EI fescue may ameliorate certain symptoms of fescue toxicosis.

  13. Ameliorating effects of traditional Chinese medicine on lipopolysaccharide -induced microcirculatory disturbances and organ injury.

    Science.gov (United States)

    Sun, Kai; Pan, Chun-Sui; Li, Quan; Furukawa, Osamu; Fan, Jing-Yu; Han, Jing-Yan

    2015-03-16

    Gram-negative bacteria are one of the major pathogens associated with severe sepsis and septic shock. LPS is a component of the outer membrane of gram-negative bacteria, which causes a systemic, uncontrolled inflammatory response in infected subjects. In microcirculation it manifests multiple insults, including leukocyte and platelet adhesion, ROS and protease overproduction, mast cell degranulation, endothelium hyperpermeabilty, hemorrhage, and microthrombi formation, ultimately results in multiorgan dysfunction, DIC, refractory shock and even death. TCM has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound traditional preparation to treat inflammation-related diseases dates back to the Han Dynasty and the medical formulary had been developed thousands of years before, which recorded a great number of classical prescriptions for treatment with infectious diseases. This review will summarize the up to date works with respect to the ameliorating effects of compound and single traditional Chinese medicine and active components on LPS-induced inflammation, including clinical trial and experimental studies regarding multiorgan injury and underlying mechanisms.

  14. Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

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    Xiao-Yuan Mao

    2014-05-01

    Full Text Available The present study was designed to probe the effects of Huperzine A (HupA on diabetes-associated cognitive decline (DACD using a streptozotocin (STZ-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT, Acetylcholinesterase (AChE, malondialdehyde (MDA, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

  15. Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats

    Science.gov (United States)

    Ibrahim, Marwa A.; Khalaf, A. A.; Galal, Mona K.; Ogaly, Hanan A.; H. M. Hassan, Azza

    2015-09-01

    The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

  16. Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

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    Jie Su

    2015-01-01

    Full Text Available Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II- induced proliferation and migration of vascular smooth muscle cells (VSMCs. Dichlorofluorescein diacetate (DCFH-DA staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS.

  17. Palatable cafeteria diet ameliorates anxiety and depression-like symptoms following an adverse early environment.

    Science.gov (United States)

    Maniam, Jayanthi; Morris, Margaret J

    2010-06-01

    Early trauma contributes to psychosocial disorders later in life. An adverse early environment induced by maternal separation (MS) is known to alter behavioural and stress responses in rats. Palatable food dampens stress responses. We investigated the influence of palatable cafeteria high-fat diet (HFD) on behavioural responses following MS or non-handling (NH), versus 15min brief separation. After littering, Sprague-Dawley rats were exposed to short separation, S15 (15min), prolonged separation, S180 (180min) daily from postnatal days 2 to 14 or were non-handled. Pups were assigned to HFD or chow at weaning. We assessed depression and anxiety-like behaviour with sucrose preference test (SPT) and elevated plus maze (EPM) respectively, and measured hypothalamic CRH and hippocampal glucocorticoid receptor (GR) expression. S180 rats showed increased anxiety-and depression-like behaviours, with increased plasma corticosterone, hypothalamic CRH, and reduced hippocampal GR expression versus S15 rats. Similar effects were observed across gender. These were normalized by provision of HFD, with greater beneficial effects in males. S15 showed no benefit of HFD. NH female rats had less adverse impacts; HFD had beneficial impact on behaviour in NH males. Thus behavioural deficits and gene expression changes induced by early life stress were ameliorated by HFD. These results highlight the important place of palatable food in reducing central stress responses supporting the therapeutic value of 'comfort food'. Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.

  18. Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

    Science.gov (United States)

    Zhang, Danqing; Kobayashi, Toshiyuki; Kojima, Tetsuo; Kanenishi, Kenji; Hagiwara, Yoshiaki; Abe, Masaaki; Okura, Hidehiro; Hamano, Yoshitomo; Sun, Guodong; Maeda, Masahiro; Jishage, Kou-ichi; Noda, Tetsuo; Hino, Okio

    2011-04-01

    Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway. © 2011 Japanese Cancer Association.

  19. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  20. Increased hemoglobin-oxygen affinity ameliorates bleomycin-induced hypoxemia and pulmonary fibrosis.

    Science.gov (United States)

    Geng, Xin; Dufu, Kobina; Hutchaleelaha, Athiwat; Xu, Qing; Li, Zhe; Li, Chien-Ming; Patel, Mira P; Vlahakis, Nicholas; Lehrer-Graiwer, Josh; Oksenberg, Donna

    2016-09-01

    Although exertional dyspnea and worsening hypoxia are hallmark clinical features of idiopathic pulmonary fibrosis (IPF), no drug currently available could treat them. GBT1118 is a novel orally bioavailable small molecule that binds to hemoglobin and produces a concentration-dependent left shift of the oxygen-hemoglobin dissociation curve with subsequent increase in hemoglobin-oxygen affinity and arterial oxygen loading. To assess whether pharmacological modification of hemoglobin-oxygen affinity could ameliorate hypoxemia associated with lung fibrosis, we evaluated GBT1118 in a bleomycin-induced mouse model of hypoxemia and fibrosis. After pulmonary fibrosis and hypoxemia were induced, GBT1118 was administered for eight consecutive days. Hypoxemia was determined by monitoring arterial oxygen saturation, while the severity of pulmonary fibrosis was assessed by histopathological evaluation and determination of collagen and leukocyte levels in bronchoalveolar lavage fluid. We found that hemoglobin modification by GBT1118 had strong antihypoxemic therapeutic effects with improved arterial oxygen saturation to near normal level. Moreover, GBT1118 treatment significantly attenuated bleomycin-induced lung fibrosis, collagen accumulation, body weight loss, and leukocyte infiltration. This study is the first to suggest the beneficial effects of hemoglobin modification in fibrotic lungs and offers a promising and novel therapeutic strategy for the treatment of hypoxemia associated with chronic fibrotic lung disorders in human, including IPF. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  1. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    Science.gov (United States)

    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  2. Doxycyclin ameliorates a starvation-induced germline tumor in C. elegans daf-18/PTEN mutant background.

    Science.gov (United States)

    Wolf, Tim; Qi, Wenjing; Schindler, Verena; Runkel, Eva Diana; Baumeister, Ralf

    2014-08-01

    Managing available resources is a key necessity of each organism to cope with the environment. The nematode C. elegans responds to nutritional deprivation or harsh environmental conditions with a multitude of developmental adaptations, among them a starvation-induced quiescence at early larval development (L1). daf-18, the C. elegans homolog of the human tumor suppressor gene PTEN, is essential for the maintenance of survival and germline stem cell arrest during the L1 diapause. We show here that daf-18 mutants, independently to their failure to maintain G2 arrest of the primordial germ cells, develop a gonad phenotype after refeeding. This highly penetrant gonadal phenotype is further enhanced by a mutation in shc-1, encoding a protein homologous to the human adaptor ShcA. Features of this phenotype are a tumor-like phenotype encompassing hyper-proliferation of germ cell nuclei and disruption/invasion of the basement membrane surrounding the gonad. The penetrance of this phenotype is reduced by decreasing starvation temperature. In addition, it is also ameliorated in a dose-dependent way by exposure to the antibiotic doxycyclin either during starvation or during subsequent refeeding. Since, in eukaryotic cells, doxycyclin specifically blocks mitochondrial translation, our results suggest that daf-18 and shc-1;daf-18 mutants fail to adapt mitochondrial activity to reduced nutritional availability during early larval developing. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Tempol Ameliorates and Prevents Mechanical Hyperalgesia in a Rat Model of Chemotherapy-Induced Neuropathic Pain.

    Science.gov (United States)

    Kim, Hee Kee; Hwang, Seon-Hee; Abdi, Salahadin

    2016-01-01

    Chemotherapy-induced neuropathic pain is difficult to treat and prevent. Tempol decreases cellular superoxide radical levels and oxidative stress. The aims of our study were to investigate the analgesic and preventive effects of tempol on paclitaxel-induced neuropathic pain in rats and to identify the associated mechanisms of action. Neuropathic pain was induced with intraperitoneally injected paclitaxel on four alternate days in male Sprague-Dawley rats. Tempol was administered systemically as a single injection and a continuous infusion before or after the injection of paclitaxel. The mechanical threshold for allodynia, protein levels, and free radical levels were measured using von Frey filaments, Western blotting, and live cell imaging, respectively. After the rats developed neuropathic pain behavior, a single intraperitoneal injection and continuous infusion of tempol ameliorated paclitaxel-induced mechanical allodynia. Systemic infusion of tempol in the early phase of the development of pain behavior prevented the development of paclitaxel-induced pain behavior. Paclitaxel increased the levels of phosphorylated protein kinase C, phosphorylated nuclear factor κB, phosphodiesterase 4D (PDE4D), IL-1β, and monocyte chemoattractant protein-1 in the lumbar dorsal root ganglia; however, tempol decreased these levels. Paclitaxel also increased superoxide levels in a culture of primary dorsal root ganglion cells and tempol decreased these levels. In conclusion, tempol alleviates and prevents chemotherapy-induced neuropathic pain in rats by reducing the levels of inflammatory cytokines and free radicals in dorsal root ganglia.

  4. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice

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    Wei Ding

    2015-07-01

    Full Text Available Background: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. Methods: CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx and Nx+Tempol (2 mmol/l in drinking water. Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Results: Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox, and elevated activation of TGF-ß/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-ß/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-ß/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways.

  5. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice.

    Science.gov (United States)

    Ding, Wei; Wang, Bin; Zhang, Minmin; Gu, Yong

    2015-01-01

    Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD) and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx) and Nx+Tempol (2 mmol/l in drinking water). Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage) was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox), and elevated activation of TGF-β/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-β/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-β/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways. © 2015 S. Karger AG, Basel.

  6. Using of Coffee and Cardamom Mixture to Ameliorate Oxidative Stress Induced in irradiated Rats

    International Nuclear Information System (INIS)

    Hamza, R.G.; Osman, N.N.

    2013-01-01

    Human exposure to ionizing radiation induced overproduction of free radicals leading to oxidative stress. This study aimed to evaluate the possibility of using of coffee and cardamom mixture; as natural antioxidant compounds ; to ameliorate oxidative stress in rats induced by exposure to ionizing radiation. Phenolic contents in coffee and essential oils in cardamom were identified by using HPLC chromatography and GC/MS analysis. Four groups of adult male rats were used; the control group (A), the second group (B) received orally the mixture extract of coffee and cardamom (60 mg/100g body weight) for 8 weeks, the third group (C) irradiated (6 Gy) and the fourth group (D) received orally the mixture extract for 8 weeks and exposed to radiation at the 4th week. The results revealed that the administration of mixture extract of coffee and cardamom to rats significantly reduced the damage effect induced by irradiation via the adjustment of the antioxidant status, decreasing of malondialdehyde content and the subsequent amending of different biochemical parameters as well as some hormones. Accordingly, it is possible to indicate that coffee-cardamom reduced the radiation exposure induced oxidative stress.

  7. Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus – insights into its mechanisms of action

    Science.gov (United States)

    Stefanska, B

    2012-01-01

    A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non-alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end-products (AGEs)-mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE-activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti-fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis. LINKED ARTICLE This article is a commentary on Lin et al., pp. 2212–2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01910.x PMID:22452372

  8. Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus - insights into its mechanisms of action.

    Science.gov (United States)

    Stefanska, B

    2012-08-01

    A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non-alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end-products (AGEs)-mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE-activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti-fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis. This article is a commentary on Lin et al., pp. 2212-2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01910.x. © 2012 The Author. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  9. Amelioration of nitrobenzene-induced nephrotoxicity by the ethanol extract of the herb Euphorbia hirta.

    Science.gov (United States)

    Suganya, Subramanian; Sophia, Dominic; Raj, Chinthamony Arul; Rathi, Muthaiyan Ahalliya; Thirumoorthi, Lakshmanan; Meenakshi, Periyasamy; Kumar, Dugganaboyana Guru; Gopalakrishnan, Velliyur Kanniyapan

    2011-07-01

    Euphorbia hirta (L.) (Euphorbiaceae) is a very popular herb amongst practitioners of traditional medicine and used in the treatment of female disorders, respiratory ailments, tumors, jaundice, digestive problems, wounds, etc. We aimed to evaluate the protective effect of E. hirta against nitrobenzene-induced nephrotoxicity in albino rats. The nephroprotective activity of the ethanol extract of E. hirta (400 mg/kg body weight) was studied in nitrobenzene-induced albino rats (1000 mg/kg body weight). The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and the levels of reduced glutathione (GSH), total thiols and vitamin C in the kidney tissues were determined. Histopathologic investigation was performed in the kidney tissue samples. Nitrobenzene administration significantly (P hirta significantly normalized the antioxidant levels. The nephroprotective activity was also supported by histopathologic studies of kidney tissue. The results indicate that the ethanol extract of E. hirta ameliorates renal dysfunction and could be used as an effective protector against nitrobenzene-induced nephrotoxicity, primarily through its antioxidant capacity.

  10. Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

    Science.gov (United States)

    Tahan, Veysel; Atug, Ozlen; Akin, Hakan; Eren, Fatih; Tahan, Gulgun; Tarcin, Ozlem; Uzun, Hafize; Ozdogan, Osman; Tarcin, Orhan; Imeryuz, Nese; Ozguner, Fehmi; Celikel, Cigdem; Avsar, Erol; Tozun, Nurdan

    2009-05-01

    Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

  11. Zingiber officinale Roscoe ameliorates anticancer antibiotic doxorubicin-induced acute cardiotoxicity in rat.

    Science.gov (United States)

    Ajith, Thekkuttuparambil Ananthanarayanan; Hema, Unnikrishnan; Aswathi, Sreedharan

    2016-07-01

    Oxidative stress (OS) has been suggested in the cardiotoxicity induced by anticancer antibiotic doxorubicin (DXN). The cardioprotective effects of aqueous ethanol extract of Zingiber officinale was evaluated against DXN-induced acute cardiac damage in rat. The results of the study demonstrated that Z. officinale significantly and dose dependently protected the cardiotoxicity induced by DXN. The activities of serum glutamate oxaloacetate transaminase and serum lactate dehydrogenase activity in the DXN alone treated group of animals were significantly (pDXN treated groups. The cardiac malondialdehyde was elevated in the DXN alone treated group and declined significantly in the Z. officinale (400 mg/kg) plus DXN treated group. The results concluded that aqueous ethanol extract of Z. officinale ameliorated DXN-induced cardiotoxicity. The protection can be ascribed to the free radical scavenging activity of Z. officinale. This protective effect may suggest the adjuvant role of Z. officinale against OS induced by cancer chemotherapeutants, which warrant further research. © 2016 Old City Publishing, Inc.

  12. Adolescents’ Sense of Community and Involvement in Playground Activities: Panacea to Ameliorate Social Vices and Delinquencies

    Directory of Open Access Journals (Sweden)

    Oluwagbemiga Paul Agboola

    2017-05-01

    Full Text Available Researchers have identified defects in the physical environments in which they interact and play, which has resulted in a decline the expected values initiated in both the social, physical and psychological developments. The role of playground in the development of adolescent’s health, moral and social standard has attracted lower interest in the recent time. The adolescent sense of community relates to a positive experience in the community open space setting such as playground and social well-being with their peers in general. Over time, little efforts have been initiated by the researchers towards these phenomena. This current study fills the gap by examining the adolescents’ sense of community through a quantitative survey via appraisal of the quality of community playground, emotional connection and effects of their participation in playground activities on ameliorating the delinquents’ behavior and social vices. Completed survey questionnaires retrieved from a total number of 69 purposive respondents who are adolescents from three towns and analyzed through relative importance index (RII via Likert scale. Results from the analysis indicated that adolescents’ positive attitudinal changes and reduction in social vices and delinquent’s behavior could be achieved through their involvements in quality and well-equipped playgrounds. Similarly, the significant role of sense of community in enhancing adolescent social participation in playground activities contributes to a major role in increasing their social well-being and togetherness. Thus, the study recommends appropriate future planning, design, and management of neighborhood playgrounds in Nigeria.

  13. Fly ash as a soil ameliorant for improving crop production--a review.

    Science.gov (United States)

    Jala, Sudha; Goyal, Dinesh

    2006-06-01

    Fly ash, a resultant of combustion of coal at high temperature, has been regarded as a problematic solid waste all over the world. Many possible beneficial applications of fly ash are being evaluated to minimize waste, decrease cost of disposal and provide value-added products. The conventional disposal methods for fly ash lead to degradation of arable land and contamination of the ground water. However fly ash is a useful ameliorant that may improve the physical, chemical and biological properties of problem soils and is a source of readily available plant macro and micronutrients. In conjunction with organic manure and microbial inoculants, fly ash can enhance plant biomass production from degraded soils. Detailed studies on the nature and composition of fly ash, conducted during the latter half of the 20th century have helped in repeatedly confirming the various useful applications of this hitherto neglected industrial waste. The purpose of this paper is to review the available information on various attributes of fly ash and explore the possibility of exploiting them for agronomic advantage.

  14. Ghrelin ameliorates nerve growth factor Dysmetabolism and inflammation in STZ-induced diabetic rats.

    Science.gov (United States)

    Zhao, Yuxing; Shen, Zhaoxing; Zhang, Dongling; Luo, Huiqiong; Chen, Jinliang; Sun, Yue; Xiao, Qian

    2017-06-01

    Diabetic encephalopathy is characterized by cognitive impairment and neuroinflammation, deficient neurotrophic support, and neuronal and synaptic loss. Ghrelin, a 28 amino acid peptide, is associated with neuromodulation and cognitive improvement, which has been considered as a potential protective agent for several neurodegenerative diseases. Here we sought to investigate the role of ghrelin in preventing diabetic-related neuropathology. We found that ghrelin attenuated astrocytic activation and reduced levels of interleukin-6 and tumor necrosis factor-α in streptozotocin-induced diabetic rats. In addition, ghrelin inhibited p38 mitogen-associated protein kinase activation. The upregulation of nerve growth factor (NGF) precursor and matrix metalloproteinase (MMP)-9 and downregulation of mature NGF and MMP-7 in the diabetic brain were reversed by ghrelin. Treatment with ghrelin elevated synaptophysin expression and synaptic density in diabetic rats. Taken together, our results demonstrate that ghrelin ameliorates diabetes-related neurodegeneration by preventing NGF dysmetabolism and synaptic degeneration through regulating MMP levels as well as inhibiting neuroinflammation.

  15. Selective Chemical Inhibition of PGC-1α Gluconeogenic Activity Ameliorates Type 2 Diabetes.

    Science.gov (United States)

    Sharabi, Kfir; Lin, Hua; Tavares, Clint D J; Dominy, John E; Camporez, Joao Paulo; Perry, Rachel J; Schilling, Roger; Rines, Amy K; Lee, Jaemin; Hickey, Marc; Bennion, Melissa; Palmer, Michelle; Nag, Partha P; Bittker, Joshua A; Perez, José; Jedrychowski, Mark P; Ozcan, Umut; Gygi, Steve P; Kamenecka, Theodore M; Shulman, Gerald I; Schreiber, Stuart L; Griffin, Patrick R; Puigserver, Pere

    2017-03-23

    Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes. On the basis of potency and bioavailability, we selected a small molecule, SR-18292, that reduces blood glucose, strongly increases hepatic insulin sensitivity, and improves glucose homeostasis in dietary and genetic mouse models of T2D. These studies have important implications for understanding the regulatory mechanisms of glucose metabolism and treatment of T2D. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Ameliorating influence of sulfur on germination attributes of canola (brassica napus l.) under chromium stress

    International Nuclear Information System (INIS)

    Jahan, S.; Iqbal, S.; Jabeen, K.; Sadaf, S.

    2015-01-01

    An experiment was performed to evaluate the role of sulfur to induce tolerance in Brassica napus L. against chromium stress by estimating the changes in germination parameters. Petriplates were assembled in Randomized Complete Block Design. A total 9 sets of treatments viz., control, chromium treated (40 and 160ppm), sulfur treated (50 and 150ppm) and sulfur (50 and 150ppm) combined with chromium (40 and 160ppm) with three replicates was used. Chromium under both concentrations was responsible for significant decline in germination parameters i.e. germination percentage, germination rate, seedling vigor index, shoot and root length, fresh weight and dry weight of seedlings. Sulfur application under chromium stress resulted in improvement of germination parameters such as germination percentage, germination rate, seedling vigor index, shoot and root length, fresh weight and dry weight of seedlings in contrast to chromium treatment. So, it can be concluded that sulfur in appropriate dose can be used to ameliorate the negative effects of chromium by increasing the germination potential of canola. (author)

  17. Evaluating the ameliorative efficacy of Spirulina platensis on spermatogenesis and steroidogenesis in cadmium-intoxicated rats.

    Science.gov (United States)

    Farag, Mayada R; Abd El-Aziz, R M; Ali, H A; Ahmed, Sahar A

    2016-02-01

    The present study was conducted to evaluate the ameliorative efficacy of Spirulina platensis (SP) on reproductive dysfunctions induced by cadmium chloride (CdCl2) in male rats. Rats (n = 40) were divided into five groups (eight rats/each). Group 1: served as control without any treatment. Group 2: Rats were administered SP (150 mg/kg body weight (BW)) in drinking water for 10 days. Group 3: Rats were subcutaneously injected with CdCl2 (2 mg/kg BW) daily for 10 days. Group 4: Rats were co-treated with both CdCl2 (2 mg/kg BW) and SP (150 mg/kg BW) daily for 10 days (SP prophylactic group). Group 5: Rats received CdCl2 for 10 days followed by administration of SP alone in drinking water daily for another 30 days with the same mentioned routes and doses (SP treatment group). From our findings, the administration of SP alone or co-administration with Cd significantly attenuated the harmful effects of Cd, suggesting its beneficial role in improving spermatogenesis and steroidogenesis after Cd exposure.

  18. L'amelioration potentielle des sciages d'epinette noire en tenant compte des noeuds

    Science.gov (United States)

    Lemieux, Hugo

    Cette recherche a pour but de determiner l'amelioration potentielle de la resistance mecanique des sciages d'epinette noire. Un echantillon de billes a ete mesure afin de caracteriser les noeuds en surface. Un sous-echantillon a ete disseque afin de caracteriser les noeuds. Ces mesures ont servi dans un modele de debitage de billes et de classement des planches qui prend en compte les noeuds. Des simulations de sciage et de classement ont ete effectuees sur toutes les billes en faisant des rotations de celles-ci. Les simulations ont determine les positions qui donnent un meilleur et un pire rendement au niveau du classement. La moitie des billes a ensuite ete sciee par rapport a une meilleure position et l'autre moitie par rapport a la pire solution. Les sciages ont ete classes visuellement par rapport aux noeuds seulement et par rapport a tous les defauts. Ils ont ensuite ete testees a destruction. L'analyse a determine que les noeuds n'ont pas d'effet sur le classement visuel des sciages mais qu'ils ont eu un effet marque sur la resistance mecanique.

  19. Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma.

    Science.gov (United States)

    Iyoda, Tomonori; Yamasaki, Satoru; Hidaka, Michihiro; Kawano, Fumio; Abe, Yu; Suzuki, Kenshi; Kadowaki, Norimitsu; Shimizu, Kanako; Fujii, Shin-Ichiro

    2018-02-01

    NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56 dim CD16 + NK cells and DNAM-1 on CD56 bright CD16 - NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration.

    Science.gov (United States)

    Bai, Long; Du, Zhibin; Du, Jingjing; Yao, Wei; Zhang, Jiaming; Weng, Zeming; Liu, Si; Zhao, Ya; Liu, Yanlian; Zhang, Xiangyu; Huang, Xiaobo; Yao, Xiaohong; Crawford, Ross; Hang, Ruiqiang; Huang, Di; Tang, Bin; Xiao, Yin

    2018-04-01

    A multifaceted coating for hard tissue implants, with favorable osteogenesis, angiogenesis, and osteoimmunomodulation abilities, would be of great value since it could improve osseointegration and alleviate prosthesis loosening. However, to date there are few coatings that fully satisfy these criteria. Herein we describe a microporous TiO 2 coating decorated with hydroxyapatite (HA) nanoparticles that is generated by micro-arc oxidation of pure titanium (Ti) and followed annealing. By altering the annealing temperature, it is possible to simultaneously tune the coating's physical (morphology and wettability) and chemical (composites and crystallinity) properties. A coating produced with micro-arc oxidization (MAO) with an annealing temperature of 650 °C (MAO-650) exhibits numerous favorable physicochemical properties, such as hybrid micro-nano morphology, superhydrophilicity, and highly crystalline HA nanoparticles. In vitro experiments reveal that the MAO-650 coating not only supports proliferation and differentiation of both osteoblasts and endothelial cells, but also inhibits the inflammatory response of macrophages and enables a favorable osteoimmunomodulation to facilitate osteo/angio-genesis. In vivo evaluation mirrors these results, and shows that the MAO-650 coating results in ameliorative osseointegration when compared with the pristine MAO coating. These data highlight the profound effect of surface physicochemical properties on the regulation of osteo/angio-genesis and osteoimmunomodulation in the enhancement of osseointegration. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  1. Portulaca oleracea Ameliorates Diabetic Vascular Inflammation and Endothelial Dysfunction in db/db Mice

    Science.gov (United States)

    Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-01-01

    Type 2 diabetes is associated with significantly accelerated rates of micro- and macrovascular complications such as diabetic vascular inflammation and endothelial dysfunction. In the present study, we investigated the protective effect of the aqueous extract of Portulaca oleracea L. (AP), an edible plant used as a folk medicine, on diabetic vascular complications. The db/db mice were treated with AP (300 mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly increased plasma level of HDL-cholesterol and insulin level. The impairment of ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP treatment in diabetic db/db mice. This study also showed that overexpression of VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of untreated db/db mice, which were significantly suppressed by treatment with AP. We also found that the insulin immunoreactivity of the pancreatic islets remarkably increased in AP treated db/db mice compared with untreated db/db mice. Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation, and prevents the development of diabetic endothelial dysfunction for the development of diabetes and its vascular complications. PMID:22474522

  2. Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus (hRSV) Infection.

    Science.gov (United States)

    Xu, Mei Ling; Wi, Ga Ram; Kim, Hyoung Jin; Kim, Hong-Jin

    2016-01-01

    Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in infants. The lack of proper prophylactics and therapeutics for controlling hRSV infection has been of great concern worldwide. Xylitol is a well-known sugar substitute and its effect against bacteria in the oral cavity is well known. However, little is known of its effect on viral infections. In this study, the effect of dietary xylitol on hRSV infection was investigated in a mouse model for the first time. Mice received xylitol for 14 d prior to virus challenge and for a further 3 d post challenge. Significantly larger reductions in lung virus titers were observed in the mice receiving xylitol than in the controls receiving phosphate-buffered saline (PBS). In addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect inflammatory status, were recruited in the mice receiving xylitol. These results indicate that dietary xylitol can ameliorate hRSV infections and reduce inflammation-associated immune responses to hRSV infection.

  3. Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Ge, Zhenzhen; Da, Yurong; Xue, Zhenyi; Zhang, Kai; Zhuang, Hao; Peng, Meiyu; Li, Yan; Li, Wen; Simard, Alain; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

    2013-03-01

    Vorinostat, a histone deacetylase inhibitor, has been used clinically as an anticancer drug and also has immunosuppressive properties. However, the underlying mechanisms of effects of vorinostat on central nervous system (CNS) inflammatory diseases remain incomplete. Here, this study investigates the effects of vorinostat on human CD14(+) monocyte-derived dendritic cells (DCs) and mouse immature DC in vitro. Furthermore, we explore the therapeutic effects and cellular mechanisms of vorinostat on animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in vivo. Our findings demonstrate that vorinostat inhibited human CD14(+) monocyte-derived DCs differentiation, maturation, endocytosis, and further inhibited mDCs' stimulation of allogeneic T-cell proliferation. In addition, vorinostat inhibited DC-directed Th1- (Type 1T helper) and Th17-polarizing cytokine production. Furthermore, vorinostat ameliorated Th1- and Th17-mediated EAE by reducing CNS inflammation and demyelination. What's more, Th1 and Th17 cell functions were suppressed in vorinostat-treated EAE mice. Finally, vorinostat suppressed expression of costimulatory molecules of DC in EAE mice. These suggest therapeutic effects of vorinostat on EAE which may by suppress DCs and DCs-mediated Th1 and Th17 cell functions. Our findings warrant further investigation in the potential of vorinostat for the treatment of human multiple sclerosis. Copyright © 2012. Published by Elsevier Inc.

  4. The use of listening devices to ameliorate auditory deficit in children with autism.

    Science.gov (United States)

    Rance, Gary; Saunders, Kerryn; Carew, Peter; Johansson, Marlin; Tan, Johanna

    2014-02-01

    To evaluate both monaural and binaural processing skills in a group of children with autism spectrum disorder (ASD) and to determine the degree to which personal frequency modulation (radio transmission) (FM) listening systems could ameliorate their listening difficulties. Auditory temporal processing (amplitude modulation detection), spatial listening (integration of binaural difference cues), and functional hearing (speech perception in background noise) were evaluated in 20 children with ASD. Ten of these subsequently underwent a 6-week device trial in which they wore the FM system for up to 7 hours per day. Auditory temporal processing and spatial listening ability were poorer in subjects with ASD than in matched controls (temporal: P = .014 [95% CI -6.4 to -0.8 dB], spatial: P = .003 [1.0 to 4.4 dB]), and performance on both of these basic processing measures was correlated with speech perception ability (temporal: r = -0.44, P = .022; spatial: r = -0.50, P = .015). The provision of FM listening systems resulted in improved discrimination of speech in noise (P Communication (P = .019 [-40.1% to -5.0%]). Eight of the 10 participants who undertook the 6-week device trial remained consistent FM users at study completion. Sustained use of FM listening devices can enhance speech perception in noise, aid social interaction, and improve educational outcomes in children with ASD. Copyright © 2014 Mosby, Inc. All rights reserved.

  5. Brown adipose tissue transplantation ameliorates male fertility impairment caused by diet-induced obesity.

    Science.gov (United States)

    Liu, Hui; Liu, Xiaomeng; Wang, Li; Sheng, Nan

    Populations with obesity or overweight have a high incidence of infertility. We hypothesised that brown adipose tissue (BAT) transplantation can attenuate the impairment of male fertility caused by diet-induced obesity. BATs were transplanted from male donor mice into age and sex matched recipient mice fed high-fat diets (HFD). Sperm motility experiment was conducted after surgical procedure. X-ray computed tomography scanning, biochemical assay, real-time PCR and western blot analysis were performed. BAT transplantation reduced body fat and epididymal fat mass, as well as triglycerides (TG) content in testis and epididymis and total cholesterol (TCHO) contents in epididymis compared with the HFD group. Sperm motility and progressiveness were recovered and mRNA and protein levels of genes related to sperm motility such as cullin 3 (Cul3), peroxisome proliferator activated receptor alpha (PPARα) and its down-stream genes were significantly down-regulated post BAT transplantation. BAT transplantation partially ameliorated impairment of male fertility caused by diet-induced obesity. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  6. Fresh garlic amelioration of high-fat-diet induced fatty liver in albino rats.

    Science.gov (United States)

    Qamar, Aisha; Siddiqui, Asma; Kumar, Hemant

    2015-10-01

    To observe the effect of fresh garlic on high-fat-diet-induced fatty liver changes. The experimental study was conducted at the Jinnah Postgraduate Medical Centre, Karachi, from October to November 2008, and comprised adult albino rats weighing 200-240g each. The rats were divided into 5 groups according to dietary regimen for eight weeks each. Group A received control diet; Group B received high saturated fat diet; Group C received high unsaturated fat diet; Group D received high saturated fat diet with fresh garlic; and Group E received high unsaturated fat diet with garlic for 8 weeks. Liver tissue slides were stained with Oil red-O and haematoxylin and Periodic acid-Schiff-haematoxylin. The 50 rats in the study were divided into five groups of 10(20%) each. There was marked deposition of fat in hepatocyte along with marked decrease in glycogen content in liver of rats in Groups B and C, with Group B showing more marked changes. The changes in fat and glycogen content were reversed and ameliorated close to Group A in rats belonging to Groups D and E. Fresh garlic minimised the high-fat-diet-induced fatty liver changes in rats.

  7. Proline Activity and Growth of Oil Palm affected by Aluminium Toxicity and Silica as Ameliorant

    Directory of Open Access Journals (Sweden)

    Annisa Khoiriyah

    2017-07-01

    Full Text Available The research aims to investigate the effects of silica (Si as an ameliorant on the proline compound concentration and the growth response of oil palm exposed to aluminum toxicity. The research was arranged in a complete randomized block design with 8 blocks as replications. The first factor was Al toxicity which consisted of two levels as without and with Al toxicity. Al toxicity treatment was applied by giving 300 ppm of Al concentrate along with watering activity regularly. The second factor was the application of silica which consisted of four levels as 0, 32, 64 g/plant. Proline and growth activities of leaf area, plant height, number of leaves, and dry weight were observed in the research. The data subjected to analysis of variance (ANOVA at 5% test level. If the result of ANOVA showed significant differences among treatments, then the data would have been analyzed by Duncan’s Multiple Range Test (DMRT at 5% test level. The results of the research provide information that Al toxicity increases proline compound in the plant tissues and decreases leaf area, plant height, number of leaves, and dry weight of Oil Palm. Applying Si at the level of 64 g/plant could increase proline concentrate and dry weight of oil palm exposed to A1 toxicity. Proline compound in the plant tissues did not have any correlation with the growth of oil palm. Thus, this case indicated that proline was a product and not a plant tolerant mechanism of Al toxicity.

  8. Perk Ablation Ameliorates Myelination in S63del-Charcot–Marie–Tooth 1B Neuropathy

    Directory of Open Access Journals (Sweden)

    Nicolò Musner

    2016-04-01

    Full Text Available In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot–Marie–Tooth disease type 1B (CMT1B–S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment: Perk haploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/− compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition, Perk deficiency in other cells may contribute to demyelination in a non–Schwann-cell autonomous manner.

  9. Perk Ablation Ameliorates Myelination in S63del-Charcot-Marie-Tooth 1B Neuropathy.

    Science.gov (United States)

    Musner, Nicolò; Sidoli, Mariapaola; Zambroni, Desireè; Del Carro, Ubaldo; Ungaro, Daniela; D'Antonio, Maurizio; Feltri, Maria L; Wrabetz, Lawrence

    2016-01-01

    In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot-Marie-Tooth disease type 1B (CMT1B)-S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment:Perkhaploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/- compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition,Perkdeficiency in other cells may contribute to demyelination in a non-Schwann-cell autonomous manner. © The Author(s) 2016.

  10. Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

    Science.gov (United States)

    Pahwa, Priyanka; Goel, Rajesh Kumar

    2016-04-01

    Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1α pathway.

    Science.gov (United States)

    Liu, Peng; Zou, Dan; Yi, Long; Chen, Mingliang; Gao, Yanxiang; Zhou, Rui; Zhang, Qianyong; Zhou, Yong; Zhu, Jundong; Chen, Ka; Mi, Mantian

    2015-01-01

    Acute hypobaric hypoxia (HH) causes persistent cognitive impairment, affecting memory function specifically. Mitochondrial dysfunction and synaptic morphological change were the prominent pathological features of HH exposure on brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is reported to prevent ischemia induced by neuronal injury. This study investigated the efficacy of quercetin to ameliorate HH-induced memory deficit. Rats were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and received quercetin daily (50, 75 or 100 mg/kg·bw) via gavage during the period of exposure. Cognitive performance was assessed by the Morris water maze test. In vitro, the effect of quercetin was tested in hippocampus tissue. Quercetin, especially at 100 mg/kg·bw, significantly reduced HH-induced memory decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions were ameliorated by quercetin. Furthermore, quercetin regulated the expression of sirtuin 1(Sirt1), PGC-1α, and the proteins related with mitochondrial biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF), showing the PGC-1α/FNDC5/BNDF pathways might be involved in neuronal adaptation. The results suggest quercetin has prophylactic potential for amelioration of HH-induced memory impairment, which is associated with the mitochondrial and neuronal adaptation in hippocampus.

  12. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.

    Science.gov (United States)

    Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Xu, Lin; Zhang, Zhi-Jun

    2015-01-01

    Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.

  13. Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

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    Abbaszadeh A.

    2017-06-01

    Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

  14. Salmonella enterica serovar Typhimurium infection-induced CD11b+ Gr1+ cells ameliorate allergic airway inflammation.

    Science.gov (United States)

    Ganesh, Venkateswaran; Baru, Abdul Mannan; Hesse, Christina; Friedrich, Christin; Glage, Silke; Gohmert, Melanie; Jänke, Christine; Sparwasser, Tim

    2014-03-01

    Allergies are mainly characterized as an unrestrained Th2-biased immune response. Epidemiological data associate protection from allergic diseases with the exposure to certain infectious agents during early stages of life. Modulation of the immune response by pathogens has been considered to be a major factor influencing this protection. Recent evidence indicates that immunoregulatory mechanisms induced upon infection ameliorate allergic disorders. A longitudinal study has demonstrated reduced frequency and incidence of asthma in children who reported a prior infection with Salmonella. Experimental studies involving Salmonella enterica serovar Typhimurium-infected murine models have confirmed protection from induced allergic airway inflammation; however, the underlying cause leading to this amelioration remains incompletely defined. In this study, we aimed to delineate the regulatory function of Salmonella Typhimurium infection in the amelioration of allergic airway inflammation in mice. We observed a significant increase in CD11b+ Gr1+ myeloid cell populations in mice after infection with S. Typhimurium. Using in vitro and in vivo studies, we confirmed that these myeloid cells reduce airway inflammation by influencing Th2 cells. Further characterization showed that the CD11b+ Gr1+ myeloid cells exhibited their inhibitory effect by altering GATA-3 expression and interleukin-4 (IL-4) production by Th2 cells. These results indicate that the expansion of myeloid cells upon S. Typhimurium infection could potentially play a significant role in curtailing allergic airway inflammation. These findings signify the contribution of myeloid cells in preventing Th2-mediated diseases and suggest their possible application as therapeutics.

  15. Amelioration of fatty liver index in patients with type 2 diabetes on ipragliflozin: an association with glucose-lowering effects.

    Science.gov (United States)

    Takase, Takahiro; Nakamura, Akinobu; Miyoshi, Hideaki; Yamamoto, Chiho; Atsumi, Tatsuya

    2017-03-31

    In this study, we investigated the ameliorating effects of ipragliflozin on fatty liver in patients with type 2 diabetes. The factors that influenced the amelioration of fatty liver were also examined. Analysis included data of 21 Japanese patients with type 2 diabetes obtained from our prospective observational study. After obtaining patients' informed consent, once-daily ipragliflozin (50 mg/day) was given for 16 weeks. In addition to several clinical parameters, body composition was also compared before and after 16 weeks of treatment. The extent of fatty liver was estimated using a fatty liver index (FLI). After 16 weeks, FLI significantly decreased, from 70.1 ± 19.4 to 60.3 ± 25.5 (p = 0.0009) as well as levels of fasting plasma glucose (FPG), HbA1c, body weight, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and fat mass. To reveal the factors influencing the FLI changes observed on ipragliflozin treatment, correlations between changes in FLI and several other measured parameters were examined. Changes in FPG (correlation coefficient = 0.4683, p = 0.0323) and HbA1c (correlation coefficient = 0.4383, p = 0.0469) showed significant positive correlations with changes in FLI. On the other hand, no correlations of changes in FLI were observed with body weight, VAT, SAT nor fat mass. In conclusion, ipragliflozin ameliorated FLI in Japanese patients with type 2 diabetes. Improvement in FLI was associated with that of glucose intolerance.

  16. MSCs ameliorates DPN induced cellular pathology via [Ca2+]ihomeostasis and scavenging the pro-inflammatory cytokines.

    Science.gov (United States)

    Chandramoorthy, Harish C; Bin-Jaliah, Ismaeel; Karari, Hussian; Rajagopalan, Prasanna; Ahmed Shariff, Mohammed Eajaz; Al-Hakami, Ahmed; Al-Humayad, Suliman M; Baptain, Fawzi A; Ahmed, Humeda Suekit; Yassin, Hanaa Z; Haidara, Mohamed A

    2018-02-01

    The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro-inflammatory cytokines TNF-α, IL-1β, IFN-ɤ and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co-culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4, IL-10 and TGF-β and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca 2+ ] i and cROS, the portent behind the NFκB/Caspase-3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p cytokine signaling and [Ca 2+ ] i homeostasis. © 2017 Wiley Periodicals, Inc.

  17. Protective and ameliorative effect of sea buckthorn leaf extract supplementation on lead induced hemato-biochemical alterations in Wistar rats

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    Rizwana Zargar

    2016-09-01

    Full Text Available Aim: To evaluate the protective and ameliorative effect of aqueous sea buckthorn leaf extract (SLE on hemato-biochemical profile in lead intoxicated Wistar rats. Materials and Methods: An experiment was conducted for 60 days. 36 adult male Wistar rats with a mean body weight of 177.8±12.6 g were divided into five groups and were subjected to various daily oral treatment regimens. Group I served as a negative control receiving only feed and water, Group II (positive control for lead received lead acetate at 250 ppm in drinking water, and Group III (positive control for SLE received SLE at 100 mg/kg b.wt. Animals in Group IV received a combination of lead acetate at 250 ppm in drinking water for the first 45 days and SLE at 100 mg/kg b.wt. throughout the experimental period of 60-day, and in Group V for the last 15 days of the trial after the administration of lead acetate until the first 45 days of the trial to study the protective and ameliorating effects of SLE, respectively. Blood samples were collected from retro-orbital fossa of each rat on 0th, 45th, and 60th day of the experiment for hemato-biochemical analysis including hemoglobin (Hb, packed cell volume (PCV, serum total protein, albumin, globulin, albumin:globulin ratio, cholesterol, urea, and creatinine. Results: Significantly (p<0.01 lower levels of serum total proteins and albumin, and a significantly (p<0.01 higher serum cholesterol, urea and creatinine levels were observed in Group II (lead intoxicated group in comparison to Group I (negative control. Administration of SLE at 100 mg/kg body wt. to lead intoxicated Wistar rats resulted in normalization of almost all the biochemical parameters studied in both the treatment Groups, i.e., IV and V (protective and ameliorative. However, the effects were more pronounced in the protective group. No effects of SLE supplementation were observed on Hb levels. PCV levels improved in protective groups, but no effect was observed in

  18. Ameliorating effect of olive oil on fertility of male rats fed on genetically modified soya bean

    Science.gov (United States)

    El-Kholy, Thanaa A. F.; Al-Abbadi, Hatim A.; Qahwaji, Dina; Al-Ghamdi, Ahmed K.; Shelat, Vishal G.; Sobhy, Hanan M.; Hilal, Mohammad Abu

    2015-01-01

    Background Genetically modified soya bean (GMSB) is a commercialized food. It has been shown to have adverse effects on fertility in animal trials. Extra virgin olive oil (EVOO) has many beneficial effects including anti-oxidant properties. The aim of this study is to elucidate if addition of EVOO ameliorates the adverse effects on reproductive organs of rats fed on GMSB containing diet. Methods Forty adult male albino rats (150–180 g) of Sprague Dawley strain were separated into four groups of 10 rats each: Group 1 – control group fed on basal ration, Group 2 – fed on basal ration mixed with EVOO (30%), Group 3 – fed on basal ration mixed with GMSB (15%), and Group 4 – fed on basal ration mixed with GMSB (15%) and EVOO (30%). This feeding regimen was administered for 65 days. Blood samples were collected to analyze serum zinc, vitamin E, and testosterone levels. Histopathological and weight changes in sex organs were evaluated. Results GMSB diet reduced weight of testis (0.66±0.06 vs. 1.7±0.06, p<0.001), epididymis (0.489±0.03 vs. 0.7±0.03, p<0.001), prostate (0.04±0.009 vs. 0.68±0.04, p<0.001), and seminal vesicles (0.057±0.01 vs. 0.8±0.04, p<0.001). GMSB diet adversely affected sperm count (406±7.1 vs. 610±7.8, p<0.001), motility (p<0.001), and abnormality (p<0.001). GMSB diet also reduced serum zinc (p<0.05), vitamin E (p<0.05), and testosterone (p<0.05) concentrations. EVOO diet had no detrimental effect. Addition of EVOO to GMSB diet increased the serum zinc (p<0.05), vitamin E (p<0.05), and testosterone (p<0.05) levels and also restored the weights of testis (1.35±0.16 vs. 0.66±0.06, p<0.01), epididymis (0.614±0.13 vs. 0.489±0.03, p<0.001), prostate (0.291±0.09 vs. 0.04±0.009, p<0.001), seminal vesicle (0.516±0.18 vs. 0.057±0.01, p<0.001) along with sperm count (516±3.1 vs. 406±7.1, p<0.01), motility (p<0.01), and abnormality (p<0.05). Conclusion EVOO ameliorates the adverse effects of GMSB on reproductive organs in adult male

  19. Ameliorating effect of olive oil on fertility of male rats fed on genetically modified soya bean

    Directory of Open Access Journals (Sweden)

    Thanaa A. F. El-Kholy

    2015-09-01

    Full Text Available Background: Genetically modified soya bean (GMSB is a commercialized food. It has been shown to have adverse effects on fertility in animal trials. Extra virgin olive oil (EVOO has many beneficial effects including anti-oxidant properties. The aim of this study is to elucidate if addition of EVOO ameliorates the adverse effects on reproductive organs of rats fed on GMSB containing diet. Methods: Forty adult male albino rats (150–180 g of Sprague Dawley strain were separated into four groups of 10 rats each: Group 1 – control group fed on basal ration, Group 2 – fed on basal ration mixed with EVOO (30%, Group 3 – fed on basal ration mixed with GMSB (15%, and Group 4 – fed on basal ration mixed with GMSB (15% and EVOO (30%. This feeding regimen was administered for 65 days. Blood samples were collected to analyze serum zinc, vitamin E, and testosterone levels. Histopathological and weight changes in sex organs were evaluated. Results: GMSB diet reduced weight of testis (0.66±0.06 vs. 1.7±0.06, p<0.001, epididymis (0.489±0.03 vs. 0.7±0.03, p<0.001, prostate (0.04±0.009 vs. 0.68±0.04, p<0.001, and seminal vesicles (0.057±0.01 vs. 0.8±0.04, p<0.001. GMSB diet adversely affected sperm count (406±7.1 vs. 610±7.8, p<0.001, motility (p<0.001, and abnormality (p<0.001. GMSB diet also reduced serum zinc (p<0.05, vitamin E (p<0.05, and testosterone (p<0.05 concentrations. EVOO diet had no detrimental effect. Addition of EVOO to GMSB diet increased the serum zinc (p<0.05, vitamin E (p<0.05, and testosterone (p<0.05 levels and also restored the weights of testis (1.35±0.16 vs. 0.66±0.06, p<0.01, epididymis (0.614±0.13 vs. 0.489±0.03, p<0.001, prostate (0.291±0.09 vs. 0.04±0.009, p<0.001, seminal vesicle (0.516±0.18 vs. 0.057±0.01, p<0.001 along with sperm count (516±3.1 vs. 406±7.1, p<0.01, motility (p<0.01, and abnormality (p<0.05. Conclusion: EVOO ameliorates the adverse effects of GMSB on reproductive organs in adult male

  20. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  1. Craving Behavior Intervention in Ameliorating College Students' Internet Game Disorder: A Longitudinal Study.

    Science.gov (United States)

    Deng, Lin-Yuan; Liu, Lu; Xia, Cui-Cui; Lan, Jing; Zhang, Jin-Tao; Fang, Xiao-Yi

    2017-01-01

    Craving, as a central feature of addiction and a precursor of relapse, is targeted recently in addiction intervention. While Internet gaming disorder (IGD), conceptualized as a behavioral addiction, is lack of effective treatment practice and exploration of its mechanism. This research aims to test the effectiveness and detect the active ingredients of craving behavior intervention (CBI) in mitigation of IGD among young adults. A total of 63 male college students with IGD were assigned into the intervention group (six-session CBI intervention) or the waiting-list control group. Structured questionnaires were administered at pre-intervention (T1), post-intervention (T2), 3-month follow-up (T3), and 6-month follow-up (T4). Compared to the control group, a significant decrease in the severity of IGD in intervention group was found at post-intervention and lasting to 6 months after intervention. The value changes of craving could partially mediate the relationship between intervention and changes of IGD among all effects tests (immediate, T2-T1; short-term, T3-T1; and long-term effects, T4-T1). Further, explorations of the active ingredients of intervention found depression relief and shift of psychological needs from Internet to real life significantly predict craving amelioration at both post-intervention and 6-month follow-up. Although preliminary, the current study provides evidence for the value of craving-aimed intervention practice in IGD treatment and identifies two potential active ingredients for mitigation of craving, and the long-term therapeutic benefits are further conferred. Registry name: The behavioral and brain mechanism of IGD; URL: https://www.clinicaltrials.gov/ct2/show/NCT02550405; Registration number: NCT02550405.

  2. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway

    International Nuclear Information System (INIS)

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-01-01

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5 mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10 mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes

  3. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

    Science.gov (United States)

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

  4. Interleukin-12 (IL-12) ameliorates the effects of porcine respiratory and reproductive syndrome virus (PRRSV) infection.

    Science.gov (United States)

    Carter, Quincy L; Curiel, Rafael E

    2005-08-15

    Porcine respiratory and reproductive syndrome virus (PRRSV) disease, one of the most economically significant viral diseases in the swine industry, is characterized by miscarriages, premature farrowing, stillborn pigs, and respiratory disease associated with death and chronic poor performance of nursing and weaned pigs. Interleukin-12 (IL-12) is a key component in driving the development of cell-mediated immunity as well as stimulating interferon-gamma (IFN-gamma) production from T cells and natural killer cells. Although some studies have investigated the use of IL-12 as a vaccine adjuvant in swine, little is known about its effectiveness as a treatment against viral diseases in swine. The present study investigated whether recombinant porcine IL-12 (rpIL-12) enhances the immune response and thereby diminishes the effects of PRRSV infection in young pigs. Interestingly, in vitro experiments demonstrated that rpIL-12 is capable of inducing swine pulmonary alveolar macrophages (PAMs), the target cells of PRRSV, to produce IFN-gamma in a dose and time dependent manner. In addition, in vitro studies also revealed that rpIL-12 treatment was capable of significantly reducing PRRSV viral titers in PAMs. In vivo administration of rpIL-12 significantly decreased PRRSV titers in the lungs and blood of infected animals. Furthermore, treatment with rpIL-12 prevented significant growth retardation in PRRSV-infected animals. Finally, in response to viral antigen recall challenge, PAMs isolated from rpIL-12-treated/PRRSV-infected animals produced greater amounts of IFN-gamma and lesser amounts of interleukin-10 than PAMs isolated from non-rpIL-12-treated/PRRSV-infected animals. Taken together our data indicate that treatment with rpIL-12 may provide an effective approach to control or ameliorate PRRSV-induced disease in swine.

  5. Physiological integration ameliorates negative effects of drought stress in the clonal herb Fragaria orientalis.

    Directory of Open Access Journals (Sweden)

    Yunchun Zhang

    Full Text Available Clonal growth allows plants to spread horizontally and to establish ramets in sites of contrasting resource status. If ramets remain physiologically integrated, clones in heterogeneous environments can act as cooperative systems--effects of stress on one ramet can be ameliorated by another connected ramet inhabiting benign conditions. But little is known about the effects of patch contrast on physiological integration of clonal plants and no study has addressed its effects on physiological traits like osmolytes, reactive oxygen intermediates and antioxidant enzymes. We examined the effect of physiological integration on survival, growth and stress indicators such as osmolytes, reactive oxygen intermediates (ROIs and antioxidant enzymes in a clonal plant, Fragaria orientalis, growing in homogenous and heterogeneous environments differing in patch contrast of water availability (1 homogeneous (no contrast group; 2 low contrast group; 3 high contrast group. Drought stress markedly reduced the survival and growth of the severed ramets of F. orientalis, especially in high contrast treatments. Support from a ramet growing in benign patch considerably reduced drought stress and enhanced growth of ramets in dry patches. The larger the contrast between water availability, the larger the amount of support the depending ramet received from the supporting one. This support strongly affected the growth of the supporting ramet, but not to an extent to cause increase in stress indicators. We also found indication of costs related to maintenance of physiological connection between ramets. Thus, the net benefit of physiological integration depends on the environment and integration between ramets of F. orientalis could be advantageous only in heterogeneous conditions with a high contrast.

  6. Functional food red yeast rice (RYR) for metabolic syndrome amelioration: a review on pros and cons.

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    Patel, Seema

    2016-05-01

    Red yeast rice (RYR), the fermentation product of mold Monascus purpureus has been an integral part of Oriental food and traditional Chinese medicine, long before the discovery of their medicinal roles. With the identification of bioactive components as polyketide pigments (statins), and unsaturated fatty acids, RYR has gained a nutraceutical status. Hypercholesterolemic effect of this fermented compound has been validated and monacolin K has been recognized as the pivotal component in cholesterol alleviation. Functional similarity with commercial drug lovastatin sans the side effects has catapulted its popularity in other parts of the world as well. Apart from the hypotensive role, ameliorative benefits of RYR as anti-inflammatory, antidiabetic, anticancer and osteogenic agent have emerged, fueling intense research on it. Mechanistic studies have revealed their interaction with functional agents like coenzyme Q10, astaxanthin, vitamin D, folic acid, policosanol, and berberine. On the other hand, concurrence of mycotoxin citrinin and variable content of statin has marred its integration in mainstream medication. In this disputable scenario, evaluation of the scopes and lacunae to overcome seems to contribute to an eminent area of healthcare. Red yeast rice (RYR), the rice-based fermentation product of mold Monascus purpureus is a functional food. Its bioactive component monacolin K acts like synthetic drug lovastatin, without the severe side effects of the latter. RYR has been validated to lower cholesterol, control high blood pressure; confer anti-flammation, hypoglycaemic, anticancer and osteogenic properties. However, dose inconsistency and co-occurrence of toxin citrinin hampers its dietary supplementation prospect. Further research might facilitate development of RYR as a nutraceutical.

  7. Potential ameliorative effects of grape seed-derived polyphenols against cadmium induced prostatic deficits.

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    Lei, Yongfang; Chen, Qian; Chen, Jinglou; Liu, Dong

    2017-07-01

    Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl 2 ) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured by western blot. The levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP ameliorated the prostatic oxidative stress and fibrosis induced by CdCl 2 . GSP also inhibited the over-generation of TGF-β1 and p-Smad3, as well as enhanced the levels of Smad7, Nrf-2, HO-1, γ-GCLC and miR-133a/b. These results showed that GSP could attenuate Cd-induced prostatic deficits. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat.

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    Baitharu, Iswar; Deep, Satya Narayan; Jain, Vishal; Barhwal, Kalpana; Malhotra, Anand Swaroop; Hota, Sunil Kumar; Prasad, Dipti; Ilavazhagan, Govindasamy

    2012-03-01

    Chronic exposure to hypobaric hypoxia causes oxidative stress and neurodegeneration leading to memory impairment. The present study aimed at investigating the role of corticosterone in hypoxia induced neurodegeneration and effect of metyrapone, a corticosterone synthesis inhibitor that reduces the stress induced elevation of corticosterone without affecting the basal level, in ameliorating chronic hypobaric hypoxia induced cognitive decline. Rats were exposed to simulated altitude of 25,000 ft for 0, 3, 7, 14 and 21 days to determine the temporal alterations in corticosterone and its receptors following exposure to hypobaric hypoxia. Our results showed an elevation of corticosterone in plasma and hippocampal tissue following 7 days of exposure, which declined on prolonged hypoxic exposure for 21 days. A concomitant increase in ROS and lipid peroxidation was observed along with depletion of intracellular antioxidants. Glucocorticoid and mineralocorticoid receptors were upregulated on 3 and 7 days of hypoxic exposure. Though expression of Glut1 and Glut3 were upregulated on 3 days of hypoxic exposure, sharp decline in Glut1 expression following 7 days of hypoxic exposure leads to reduced neuronal glucose uptake. Administration of metyrapone from 3rd to 7th day of hypoxic exposure to suppress hypoxia induced increase in corticosterone levels resulted in reduced oxidative damage, neurodegeneration and improvement of intracellular energy status. The metyrapone treated hypoxic animals performed better in the Morris Water Maze. Further, administration of exogenous corticosterone along with metyrapone during hypoxic exposure blunted the neuroprotective effect of metyrapone indicating a role for corticosterone in mediating hypobaric hypoxia induced neurodegeneration and memory impairment. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice.

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    Tang, Yujiao; Choi, Eun-Ju; Han, Weon Cheol; Oh, Mirae; Kim, Jin; Hwang, Ji-Young; Park, Pyo-Jam; Moon, Sang-Ho; Kim, Yon-Suk; Kim, Eun-Kyung

    2017-05-01

    Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/μM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.

  10. Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and Histopathology in Kidney of Wistar Rat.

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    Suliman Al-Gebaly, Asma

    2017-01-01

    Cadmium (Cd) is a non-essential metal whose dispersion in the environment has increased recently, Cd may enhance cell oxidative stress that leads to DNA damage and apoptotic cell death. The study aimed to evaluate the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced oxidative stress and histopathology of the kidney of Wistar rats. Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1) for five weeks with two groups pre-treated with 'Arctium lappa' administration, 100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test to determine the difference among means using the JMP version 12. Results revealed that cadmium induced a significant disorganization (pArctium lappa kg-1 b.wt., showed a slightly less hypercellularity of glomerulus and reduction in the cell tail (59 μm). Furthermore, histological sections of kidney of rats pre-treated with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules and glomerulus with a prominent urinary space beside tail length of cells was recorded as 39 μm which was lower in comparison to other groups. Moreover, cadmium induced cellular destruction of the kidney was resumed with the pre-treatment of the secondary metabolites as an antioxidant compounds that produced from plant extracts. Arctium lappa leaf extract was efficient at both applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative effect.

  11. DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice

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    Wenwen Lian

    2017-03-01

    Full Text Available Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE and butyrylcholinestease (BuChE, with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg, and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer’s disease.

  12. The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice

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    Esposito Giuseppe

    2012-12-01

    Full Text Available Abstract Background Intestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate (DSS-induced acute colitis. Methods Mice were divided into: control group, colitis group (4% DSS for four days and two pentamidine-treated colitis groups (0.8 mg/kg and 4 mg/kg. Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus (LMMP preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine. Results Pentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological/biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP. Conclusions Pentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.

  13. The Exogenous Amelioration Roles of Growth Regulators on Crop Plants Grow under Different Osmotic Potential

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    Hamdia M. Abd El-Samad

    2014-03-01

    Full Text Available The production of fresh and dry matter of maize, wheat, cotton, broad and parsley plants show a variable response to the elevation of salinity stress. The production of fresh and dry matter of shoots and roots in wheat and broad bean plants tended to decrease with increasing NaCl concentration, salt stress progressively decrease in fresh and dry matter yield of maize plants. The increase in salinization levels induced a general insignificant change in production of fresh and dry matter of both organs of parsley plants. However, salinity induced a marked increase in the values of fresh and dry matter yields of cotton plants grown at the lowest level (-0.3 MPa NaCl and a reduction at higher salinization levels. Leaf area of unsprayed plants was excesivly decreased with the rise of osmotic stress levels especially at higher salinity levels of maize, wheat, cotton, and broad bean and parsley plants. the total pigments concentration decreased with rise of salinization levels in maize and cotton, these contents remained more or less un affected up to the level of 0.6 MPa NaCl in wheat and up to 0.9 MPa in parsley plants, there above, they were significantly reduced with increasing salinity levels. In broad bean plants the total pigments contents showed a non-significant alterations at all salinity stress. Spraying the vegetative parts of the five tested plants with 200 ppm of either GA3 or kinetin completely ameliorated the deleterious effect of salinity in fresh, dry matter, leaf area and pigment contents.

  14. Amelioration of radiation nephropathy in rats by postirradiation treatment with dexamethasone and/or captopril

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    Geraci, J.P.; Sun, M.C.; Mariano, M.S. [Univ. of Washington, Seattle, WA (United States)

    1995-07-01

    Dexamethasone (DEX) and captopril are effective drugs in the treatment of radiation nephropathy in experimental animals. The aim of the present study was to determine the relative effectiveness of the two drugs and to see if their combination is more effective than either drug alone. For this purpose both kidneys of 143 rats were exposed surgically and irradiated with 13-20 Gy {gamma} rays. The surrounding tissues, with the exception of a segment of lumbar cord, were shielded. Each group had free access to acidified drinking water containing either DEX (94 {mu}g/l), captopril (500 mg/l), DEX (94{mu}g/l) + captopril (500 mg/l) or drug-free water. Dexamethasone treatment was stopped after 90 days, but animals continued to receive captopril until death. At approximately monthly intervals the animals were weighed and renal function (PUN, hematocrit, {sup 51}Cr-EDTA retention) was measured. A side effect of treatment with DEX and DEX + captopril was a reduced increase in body weight. Paralysis of the hind limbs developed in nine animals that received captopril and/or DEX treatment. The classical histological lesions associated with radiation myelopathy were not evident in these paretic rats. It is therefore suggested that paralysis may be attributed in part to drug-induced neurotoxicity in animals with impaired renal clearance. Macroscopically and histologically, nearly all the animals that survived more than 400 days had evidence of renal tumor development. dexamethasone and/or captopril appear to selectively ameliorate glomerular compared to tubular damage, based on histological findings. All three experimental treatments delayed but did not stop the progression of lethal renal injury as measured by kidney function tests and survival time. Median survival times for nontreated and captopril-DEX- and DEX + captopril-treated animals exposed to 14.5 to 19.0 Gy kidney irradiation were 175,242,261 and 395 days, respectively. 33 refs., 8 figs., 4 tabs.

  15. Amelioration Strategies Fail To Prevent Tobacco Smoke Effects On Neurodifferentiation: Nicotinic Receptor Blockade, Antioxidants, Methyl Donors

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    Slotkin, Theodore A.; Skavicus, Samantha; Card, Jennifer; Levin, Edward D.; Seidler, Frederic J.

    2015-01-01

    Tobacco smoke exposure is associated with neurodevelopmental disorders. We used neuronotypic PC12 cells to evaluate the mechanisms by which tobacco smoke extract (TSE) affects neurodifferentiation. In undifferentiated cells, TSE impaired DNA synthesis and cell numbers to a much greater extent than nicotine alone; TSE also impaired cell viability to a small extent. In differentiating cells, TSE enhanced cell growth at the expense of cell numbers and promoted emergence of the dopaminergic phenotype. Nicotinic receptor blockade with mecamylamine was ineffective in preventing the adverse effects of TSE and actually enhanced the effect of TSE on the dopamine phenotype. A mixture of antioxidants (Vitamin C, Vitamin E, N-acetyl-L-cysteine) provided partial protection against cell loss but also promoted loss of the cholinergic phenotype in response to TSE. Notably, the antioxidants themselves altered neurodifferentiation, reducing cell numbers and promoting the cholinergic phenotype at the expense of the dopaminergic phenotype, an effect that was most prominent for N-acetyl-L-cysteine. Treatment with methyl donors (Vitamin B12, folic acid, choline) had no protectant effect and actually enhanced the cell loss evoked by TSE; they did have a minor, synergistic interaction with antioxidants protecting against TSE effects on growth. Thus, components of tobacco smoke perturb neurodifferentiation through mechanisms that cannot be attributed to the individual effects of nicotine, oxidative stress or interference with one-carbon metabolism. Consequently, attempted amelioration strategies may be partially effective at best, or, as seen here, can actually aggravate injury interfering with normal developmental signals and/or by sensitizing cells to TSE effects on neurodifferentiation. PMID:25891525

  16. Hepatocyte transplantation ameliorates the metabolic abnormality in a mouse model of acute intermittent porphyria.

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    Yin, Zhaohui; Wahlin, Staffan; Ellis, Ewa C S; Harper, Pauline; Ericzon, Bo-Göran; Nowak, Greg

    2014-01-01

    Acute intermittent porphyria (AIP) is an autosomal dominant disorder characterized by insufficient porphobilinogen deaminase (PBGD) activity. When hepatic heme synthesis is induced, porphobilinogen (PBG) and 5-aminolevulinic acid (ALA) accumulate, which causes clinical symptoms such as abdominal pain, neuropathy, and psychiatric disturbances. Our aim was to investigate if hepatocyte transplantation can prevent or minimize the metabolic alterations in an AIP mouse model. We transplanted wild-type hepatocytes into PBGD-deficient mice and induced heme synthesis with phenobarbital. ALA and PBG concentrations in plasma were monitored, and the gene transcriptions of hepatic enzymes ALAS1, PBGD, and CYP2A5 were analyzed. Results were compared with controls and correlated to the percentage of engrafted hepatocytes. The accumulation of ALA and PBG was reduced by approximately 50% after the second hepatocyte transplantation. We detected no difference in mRNA levels of PBGD, ALAS1, or CYP2A5. Engraftment corresponding to 2.7% of the total hepatocyte mass was achieved following two hepatocyte transplantations. A lack of precursor production in less than 3% of the hepatocytes resulted in a 50% reduction in plasma precursor concentrations. This disproportional finding suggests that ALA and PBG produced in PBGD-deficient hepatocytes crossed cellular membranes and was metabolized by transplanted cells. The lack of effect on enzyme mRNA levels suggests that no significant efflux of heme from normal to PBGD-deficient hepatocytes takes place. Further studies are needed to establish the minimal number of engrafted hepatocytes needed to completely correct the metabolic abnormality in AIP and whether amelioration of the metabolic defect by partial restoration of PBGD enzyme activity translates into a clinical effect in human AIP.

  17. Alpha-tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells

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    Haikuo Xue

    2016-05-01

    Full Text Available Objective(s: Multiple sclerosis (MS is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E is an important component of human diet with antioxidant activity, which protects the body’s biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE, the animal model of MS, and treated EAE with α-tocopherol (AT which is the main content of Vit E. Materials and Methods:Twenty C57BL/6 adult female mice were used and divided into two groups randomly. EAE was induced with myelin oligodendrocyte glycoprotein (MOG, and one group was treated with AT, at a dose of 100 mg/kg on the 3th day post-immunization with MOG, the other group was treated with 1% alcohol. Mice were euthanized on day 14, post-immunization, spleens were removed for assessing splenocytes proliferation and cytokine profile, and spinal cords were dissected to assess the infiltration of inflammatory cells in spinal cord. Results:AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-γ (Th1 cytokine, though the other cytokines were only affected slightly. Conclusion:According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS.

  18. Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption.

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    Vaziri, Nosratola D; Yuan, Jun; Khazaeli, Mahyar; Masuda, Yuichi; Ichii, Hirohito; Liu, Shuman

    2013-01-01

    Chronic kidney disease (CKD) impairs intestinal barrier function which by allowing influx of noxious products causes systemic inflammation. We have recently shown that intestinal barrier dysfunction in CKD is due to degradation of epithelial tight junction (TJ) which is, in part, mediated by influx of urea and its conversion to ammonia by microbial urease. We hypothesized that by adsorbing urea and urea-derived ammonia, oral activated charcoal (AST-120) may ameliorate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. Rats were randomized to the CKD or control groups. The CKD group was fed a chow containing 0.7% adenine for 2 weeks. They were then randomized to receive a chow with or without AST-120 (4 g/kg/day) for 2 weeks. Rats consuming regular diet served as controls. Animals were then euthanized, colons were removed and processed for Western blot and immunohistology, and plasma was used to measure endotoxin and oxidative and inflammatory markers. Compared with the controls, the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNF-α, MCP-1, CINC-3, L-selectin, ICAM-1, and malondialdehyde, and depletions of colonic epithelial TJ proteins, claudin-1, occludin, and ZO1. Administration of AST-120 resulted in partial restoration of the epithelial TJ proteins and reduction in plasma endotoxin and markers of oxidative stress and inflammation. CKD animals exhibited depletion of the key protein constituents of the colonic epithelial TJ which was associated with systemic inflammation, oxidative stress and endotoxemia. Administration of AST-120 attenuated uremia-induced disruption of colonic epithelial TJ and the associated endotoxemia, oxidative stress and inflammation. Copyright © 2013 S. Karger AG, Basel.

  19. Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway

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    Ming-Qing Huang

    2016-12-01

    Full Text Available Background/Aims: Salvianolic acid B (Sal B, a major polyphenolic compound of Salvia miltiorrhiza Bunge, has been shown to possess potential antidiabetic activities. However, the action mechanism of SalB in type 2 diabetes has not been investigated extensively. The present study was designed to investigate the effects of Sal B on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as its potential molecular mechanism. Methods: Male C57BL/KsJ-db/db mice were orally treated with Sal B (50 and 100 mg/kg or metformin (positive drug, 300 mg/kg for 6 weeks. Results: Both doses of Sal B significantly decreased fasting blood glucose, serum insulin, triglyceride and free fatty acid levels, reduced hepatic gluconeogenic gene expression and improved insulin intolerance in db/db mice. High dose Sal B also significantly improved glucose intolerance, increased hepatic glycolytic gene expression and muscle glycogen content, and ameliorated histopathological alterations of pancreas, similar to metformin. Sal B treatment resulted in increased phosphorylated AMP-activated protein kinase (p-AMPK protein expression in skeletal muscle and liver, increased glucose transporter 4 (GLUT4 and glycogen synthase protein expressions in skeletal muscle, and increased peroxisome proliferator-activated receptor alpha (PPARα and phosphorylated acetyl CoA carboxylase (p-ACC protein expressions in liver. Conclusion: Our data suggest that Sal B displays beneficial effects in the prevention and treatment of type 2 diabetes at least in part via modulation of the AMPK pathway.

  20. Fluoxetine ameliorates cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling.

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    Kentaro Miyamoto

    Full Text Available Abnormal activation of the Wnt/β-catenin signaling is implicated in the osteoarthritis (OA pathology. We searched for a pre-approved drug that suppresses abnormally activated Wnt/β-catenin signaling and has a potency to reduce joint pathology in OA. We introduced the TOPFlash reporter plasmid into HCS-2/8 human chondrosarcoma cells to estimate the Wnt/β-catenin activity in the presence of 10 μM each compound in a panel of pre-approved drugs. We found that fluoxetine, an antidepressant in the class of selective serotonin reuptake inhibitors (SSRI, down-regulated Wnt/β-catenin signaling in human chondrosarcoma cells. Fluoxetine inhibited both Wnt3A- and LiCl-induced loss of proteoglycans in chondrogenically differentiated ATDC5 cells. Fluoxetine increased expression of Sox9 (the chondrogenic master regulator, and decreased expressions of Axin2 (a marker for Wnt/β-catenin signaling and Mmp13 (matrix metalloproteinase 13. Fluoxetine suppressed a LiCl-induced increase of total β-catenin and a LiCl-induced decrease of phosphorylated β-catenin in a dose-dependent manner. An in vitro protein-binding assay showed that fluoxetine enhanced binding of β-catenin with Axin1, which is a scaffold protein forming the degradation complex for β-catenin. Fluoxetine suppressed LiCl-induced β-catenin accumulation in human OA chondrocytes. Intraarticular injection of fluoxetine in a rat OA model ameliorated OA progression and suppressed β-catenin accumulation.

  1. Ameliorative effects of rutin against metabolic, biochemical and hormonal disturbances in polycystic ovary syndrome in rats.

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    Jahan, Sarwat; Munir, Faryal; Razak, Suhail; Mehboob, Anam; Ain, Qurat Ul; Ullah, Hizb; Afsar, Tayyaba; Shaheen, Ghazala; Almajwal, Ali

    2016-12-07

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The study was commenced to assess the favorable effects of Rutin against metabolic, biochemical, histological, and androgenic aspects of polycystic ovary syndrome in rats. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) per orally (p.o) for a period of 21 days for the induction of PCOS, followed by dose of rutin (100 mg/kg and 150 mg/kg, p.o) for 15 days using 0.5% w/v CMC as vehicle. Metformin was also given as a standard control to one of the rat groups. Serum estradiol, progesterone, testosterone, serum lipid parameters, CRP and glucose levels were evaluated. Furthermore, antioxidant activity was tested using superoxide dismutase, catalase, glutathione per-oxidase and reactive-oxygen species level. Rutin flavonoid had a dose-dependent effect on androgenic levels depicting more recovery in the rutin-I treated group, while rutin-II treated groups showed better antioxidant and lipid profiles as compared with PCOS groups. A decrease in the value of C reactive protein (CRP) and a restoration in the proportion of estrous phase smears were observed in the rutin treated groups. Histopathological examination of ovary revealed a significant decrease in the number of cystic follicles in post treated groups. The effects observed with rutin were moderately similar to that with standard metformin, a widely used treatment drug for PCOS. The study provides evidence for the potential ameliorative effects of rutin against clinical and biochemical features of PCOS.

  2. Rho-kinase inhibition ameliorates metabolic disorders through activation of AMPK pathway in mice.

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    Kazuki Noda

    Full Text Available BACKGROUND: Metabolic disorders, caused by excessive calorie intake and low physical activity, are important cardiovascular risk factors. Rho-kinase, an effector protein of the small GTP-binding protein RhoA, is an important cardiovascular therapeutic target and its activity is increased in patients with metabolic syndrome. We aimed to examine whether Rho-kinase inhibition improves high-fat diet (HFD-induced metabolic disorders, and if so, to elucidate the involvement of AMP-activated kinase (AMPK, a key molecule of metabolic conditions. METHODS AND RESULTS: Mice were fed a high-fat diet, which induced metabolic phenotypes, such as obesity, hypercholesterolemia and glucose intolerance. These phenotypes are suppressed by treatment with selective Rho-kinase inhibitor, associated with increased whole body O2 consumption and AMPK activation in the skeletal muscle and liver. Moreover, Rho-kinase inhibition increased mRNA expression of the molecules linked to fatty acid oxidation, mitochondrial energy production and glucose metabolism, all of which are known as targets of AMPK in those tissues. In systemic overexpression of dominant-negative Rho-kinase mice, body weight, serum lipid levels and glucose metabolism were improved compared with littermate control mice. Furthermore, in AMPKα2-deficient mice, the beneficial effects of fasudil, a Rho-kinase inhibitor, on body weight, hypercholesterolemia, mRNA expression of the AMPK targets and increase of whole body O2 consumption were absent, whereas glucose metabolism was restored by fasudil to the level in wild-type mice. In cultured mouse myocytes, pharmacological and genetic inhibition of Rho-kinase increased AMPK activity through liver kinase b1 (LKB1, with up-regulation of its targets, which effects were abolished by an AMPK inhibitor, compound C. CONCLUSIONS: These results indicate that Rho-kinase inhibition ameliorates metabolic disorders through activation of the LKB1/AMPK pathway, suggesting that

  3. Garlic ameliorates histological changes in the uterine epithelium of lead induced mice

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    Waseem, N.; Butt, S.A.; Hamid, S.

    2015-01-01

    To evaluate the protective role of garlic extract on the histology of the uterine epithelium exposed to lead acetate in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College in collaboration with National Institute of health from April to June 2013. Material and Methods: Thirty female BALBc mice were selected. Ten animals were placed in each group. Group A being the control was given normal diet. Group B was given lead acetate at a dose of 30 mg/kg/day. Group C was given lead acetate 30 mg/kg/day and garlic extract 500 mg/kg/day through oral gavage tube for 60 days. Animals were sacrificed and dissected at the end of 60 days. Right uterine horn was processed, embedded and stained for histological study. Height of epithelium was measured. It was taken from apical to basal end of the cells. Results: There was increase in height of the lining epithelium of uterus in group B, mean value 19.70 ± 4.81 meu m when compared to Group A, with mean value 13.25 ± 2.37 meu m. The height of the epithelium was relatively reduced in group C, with mean value 14.50 ± 2.30 meu m when compared with group B. In group C results were same as Group A. The p values were 0.001 when group A was compared to group B, 0.688 when group A was compared to group C and 0.005 when group B was compared to group C. Conclusion: The height of epithelium was markedly increased in lead acetate treated group which returned to normal when co treated with garlic extract. Hence garlic ameliorated the changes induced by lead. (author)

  4. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells

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    Ma Wei-Hsien

    2011-08-01

    Full Text Available Abstract Background Spinocerebellar ataxia (SCA refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model. Method Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain. Results Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice. Conclusion Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor

  5. Role of Some Antioxidants in Ameliorating Disturbances Caused by Gamma Radiation in Female Rats

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    El-Sherbiny, E. M.; Bayomi, M. M.; Addel-Aziz, S. M.

    2007-01-01

    The aim of this research is to investigate the role of supplemental antioxidant vitamins against some sex hormone and trace element disturbances in female rats 1 hour post exposure to 7.0 Gy of gamma radiation as a single dose using 60 Co source. Vitamins C and E were orally administered daily for 2 weeks in doses of 100 mg/kg and 25 mg/kg body weight, respectively. Total number of 48 female albino rats were equally divided into 4 groups; irradiated group (n = 12), vitamin C administered group (n = 12), vitamin E administered group (n = 12) and rats administered vitamin C followed immediately by vitamin E (n =12) post irradiation, in addition to the normal control group (n = 10). The results of this study revealed a significant reduction in serum estradiol level and highly significant reductions in serum progesterone level, zinc and selenium concentrations of female rats exposed to gamma rays, compared to control. Concerning groups administered vitamins, rats administered vitamin C showed a significant improvement in estradiol and progesterone levels, reaching the levels of control group and a non-significant improvement in serum zinc and selenium concentrations was recorded. Vitamin E administered group revealed a high significant increase in serum estradiol level accompanied with an improvement in progesterone, whereas a significant decrease in zinc was found and a significant amelioration in selenium concentration was recorded in comparison with control values. Administration of vitamin E followed immediately by vitamin C resulted in a significant increase in estradiol level and a remarkable improvement in the level of progesterone. Slight significant reduction in zinc was noticed, whereas selenium concentrations were reached normal levels in both E and C and and E groups in comparison with the other groups

  6. Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

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    Lei Wang

    Full Text Available Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1 expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these

  7. Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

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    Mohd Nazri Abu

    2015-01-01

    Full Text Available The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC which received standard rodent diet, the high fat diet (HFD which received high fat diet only, the high fat diet treated with T. crispa (HFDTC, and the high fat diet treated with orlistat (HFDO. After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05 reduced the body weight (41.14 ± 1.40%, adiposity index serum levels (4.910 ± 0.80%, aspartate aminotransferase (AST: 161 ± 4.71 U/L, alanine aminotransferase (ALT: 100.95 ± 3.10 U/L, total cholesterol (TC: 18.55 ± 0.26 mmol/L, triglycerides (TG: 3.70 ± 0.11 mmol/L, blood glucose (8.50 ± 0.30 mmo/L, resistin (0.74 ± 0.20 ng/mL, and leptin (17.428 ± 1.50 ng/mL hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL and C-peptide (136.48 pmol/L hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.

  8. Chromium, selenium, and zinc multimineral enriched yeast supplementation ameliorates diabetes symptom in streptozocin-induced mice.

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    Liu, Jun; Bao, Wei; Jiang, Man; Zhang, Yan; Zhang, Xiping; Liu, Liegang

    2012-05-01

    Chromium, selenium, and zinc malnutrition has been implicated in the pathogenesis of diabetic mellitus. This study aims to investigate the effects of novel multiminerals-enriched yeast (MMEY) which are minerals supplementation containing elevated levels of chromium, selenium, and zinc simultaneously in a diabetic animal model. Streptozocin-induced diabetic male Balb/c mice (n = 80) were randomly divided into diabetes control group and three treatment groups. They were administrated oral gavages with low, medium, or high doses of MMEY, respectively. Meanwhile, healthy male Balb/c mice (n = 40) of the same body weight were randomly assigned into normal control group and high dose of MMEY control group. After 8 weeks duration of treatment, the animals were sacrificed by cervical dislocation. Serum glucose concentrations, lipid profiles, oxidative/antioxidant, and immunity status were determined. No significant adverse effects were observed in the high-dose MMEY control group. Treatment of the diabetic mice with medium- or high-dose MMEY significantly decreased serum glucose, triglyceride, total cholesterol, and malondialdehyde and increased high-density lipoprotein cholesterol, glutathione, and the activities of superoxide dismutase and glutathione peroxidase. In addition, MMEY ameliorated the pathological damage of the pancreatic islets, elevated the thymus or spleen coefficient, and increased the expressions of interleukin-2 and -4 in spleen lymphocytes compared with unsupplemented diabetic mice. In conclusion, these results indicate that supplemental MMEY inhibits hyperglycemia, abates oxidative stress, modulates disorders of lipid metabolism, and reduces the impairment of immune function in diabetic mice; especially notable are the protective effects of medium doses of MMEY on the islet cells of diabetic mice.

  9. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

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    Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

    2014-02-18

    Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

  10. Silymarin ameliorates metabolic dysfunction associated with Diet-induced Obesity via activation of farnesyl X receptor

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    Ming Gu

    2016-09-01

    Full Text Available AbstractBACKGROUND AND PURPOSESilymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis and other types of toxic liver damage. . Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. EXPERIMENTAL APPROACHC57BL/6 mice were fed high-fat diet (HFD for 3 months to induce obesity, insulin resistance, hyperlipidaemia and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. FXR and NF-κB transactivities were analysed in liver using a gene reporter assay based onquantitative RT-PCR.KEY RESULTSSilymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signalling, which was enhanced by FXR activation. CONCLUSIONS AND IMPLICATIONSOur results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signalling. Key words: silymarin; silybin; metabolic syndrome; non-alcoholic fatty liver disease; farnesyl X receptorAbbreviationsALT, alanine aminotransferase; AST, aspartate transaminase; BA, bile acid; DIO, diet-induced obesity; CA, cholic acid; DMSO, dimethylsulfoxide; FXR, farnesyl X receptor; HDL-c, high density lipoprotein cholesterol; HF, high-fat; IPITT, intraperitoneal insulin tolerance test; LDL-c, low density lipoprotein cholesterol; NAFLD, non-alcoholic fatty liver disease; NF-κB, nuclear factor kappa B; NR, nuclear receptor; MS, metabolic syndrome

  11. siRNA-mediated c-Rel knockdown ameliorates collagen-induced arthritis in mice.

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    Fan, Tingting; Zhong, Fuhua; Liu, Ruiling; Chen, Youhai H; Wang, Ting; Ruan, Qingguo

    2018-03-01

    Previous studies have shown that inflammatory mediators involved in the development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor-κB (Rel/NF-κB) transcription factor family. c-Rel, a member of the Rel/NF-κB family that is preferentially expressed by immune cells, is a risk factor for several inflammatory diseases including RA. In the current study, we investigated whether targeting c-Rel can be used to treat collagen-induced arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by nanoparticles was used to knockdown the expression of c-Rel. Our results showed that siRel treatment significantly ameliorated collagen-induced arthritis. Further study revealed that c-Rel expression in the dendritic cells and macrophages from mice treated with siRel was significantly down-regulated. Consistent with the phenotypical result, the expression of inflammatory cytokines TNF-α, IL-1β, IL-6, IL-12 and IL-23 by peritoneal macrophages and splenocytes were significantly decreased. In addition, attenuated systemic and collagen-specific Th1 and Th17 immune responses were observed. Furthermore, we found that the expression of inflammatory cytokines was significantly down-regulated and the infiltration of CD3 + T cells and F4/80 + macrophages was markedly reduced in hind paws of mice treated with siRel. Collectively, our study provides strong evidence that siRNA-mediated c-Rel knockdown can suppress the development of collagen-induced arthritis in mice. Therefore, blocking c-Rel may represent an attracting strategy for the treatment of human rheumatoid arthritis. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis.

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    Lizak, Nathaniel; Lugaresi, Alessandra; Alroughani, Raed; Lechner-Scott, Jeannette; Slee, Mark; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Duquette, Pierre; Girard, Marc; Prat, Alexandre; Grammond, Pierre; Hupperts, Raymond; Grand'Maison, Francois; Sola, Patrizia; Pucci, Eugenio; Bergamaschi, Roberto; Oreja-Guevara, Celia; Van Pesch, Vincent; Ramo, Cristina; Spitaleri, Daniele; Iuliano, Gerardo; Boz, Cavit; Granella, Franco; Olascoaga, Javier; Verheul, Freek; Rozsa, Csilla; Cristiano, Edgardo; Flechter, Shlomo; Hodgkinson, Suzanne; Amato, Maria Pia; Deri, Norma; Jokubaitis, Vilija; Spelman, Tim; Butzkueven, Helmut; Kalincik, Tomas

    2017-03-01

    To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy. The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted. For the EDSS 3-6, 4-6 and 6-6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92-1.11) and postbaseline (2.15-2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58-3.07; p<0.001). A greater proportion of each epoch treated with higher efficacy therapies was associated with lower risk of reaching the outcome disability step (HRs 0.72-0.91 per 25%; p≤0.02). 3 sensitivity analyses confirmed these results. Disease progression during moderately advanced and advanced MS is highly variable and amnesic to prior disease activity. Lower relapse rates and greater time on higher efficacy immunomodulatory therapy after reaching EDSS steps 3, 4 and 6 are associated with a decreased risk of accumulating further disability. Highly effective immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced relapse-onset MS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. LPS ameliorates renal ischemia/reperfusion injury via Hsp27 up-regulation.

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    He, Kang; Xia, Lei; Zhang, Jianjun

    2018-03-01

    We have recently reported lipopolysaccharide (LPS) pretreatment attenuated renal ischemia/reperfusion injury (IRI), but the exact mechanism remains to be well elucidated. It was reported that heat shock protein (Hsp) 27 was up-regulated after administration of LPS, but whether a direct link existed between Hsp27 up-regulation and LPS-induced protection against renal IRI is still unknown. Mice were exposed to IRI or sham procedure, with pretreatment of LPS or not. Quercetin, an inhibitor of Hsp27 synthesis, was used, and an RNA interference with adenovirus vector using short hairpin RNA targeting Hsp27 was developed for inhibition of Hsp27 in mice. In addition, mice trans-infected with adenovirus vector encoding Hsp27 were used to testify the role of Hsp27 overexpression in LPS-induced renoprotection. Renal function, histological damage, inflammatory reaction, oxidative stress and apoptosis indices were measured. Western blot analysis was used to detect expression of Hsp27. We found LPS pretreatment stimulated renal up-regulation of Hsp27 and reduced renal IRI proven by less renal dysfunction, histological damage, inflammatory reaction, oxidative stress and apoptosis. It was observed that inhibition of Hsp27 synthesis by Quercetin abolished LPS-induced renoprotective effects. After renal knockdown of Hsp27, LPS-induced tolerance against renal IRI was largely removed. Mice with Hsp27 overexpression showed significantly improved renal function after IRI and LPS combined with Hsp27 overexpression had a synergistic effect on protection against renal IRI. Administration of LPS produces protective effects against renal IRI via Hsp27 up-regulation. Preconditional Hsp27 up-regulation might have a great potential for the treatment of renal IRI via ameliorating apoptosis.

  14. Rho, a Fraction From Rhodiola crenulate, Ameliorates Hepatic Steatosis in Mice Models

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    Qin Yi

    2018-03-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD, which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD-induced obesity (DIO mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT, glucose tolerance test (GTT, and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in liver.

  15. Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.

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    de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

    2016-10-06

    Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1 +/- mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

  16. Aronia melanocarpa Extract Ameliorates Hepatic Lipid Metabolism through PPARγ2 Downregulation.

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    Chung-Hwa Park

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM, known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD or to FL83B cells treated with free fatty acid (FFA. Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay. In mice, AM significantly reduced the body and liver weight, lipid accumulation in the liver, and levels of biochemical markers such as fatty acid synthase, hepatic triglyceride and leptin. Serum transaminases, indicators for hepatocyte injury, were also suppressed, while superoxide dismutase activity and liver antioxidant capacity were significantly increased. In FL83B cells, AM significantly reduced FFA-induced lipid droplet accumulation. Protein synthesis of an adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2 was inhibited in vivo. Furthermore, transcriptional activity of PPARγ2 was down-regulated in vitro, and mRNA expression of PPARγ2 and its downstream target genes, adipocyte protein 2 and lipoprotein lipase were down-regulated by AM both in vitro and in vivo. These results show beneficial effects of AM against hepatic lipid accumulation through the inhibition of PPARγ2 expression along with improvements in body weight, liver functions, lipid profiles and antioxidant capacity suggesting the potential therapeutic efficacy of AM on NAFLD.

  17. Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

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    Miao Shen

    2013-01-01

    Full Text Available Background. Hepatic ischemia-reperfusion (I/R injury is a pivotal clinical problem occurring in many clinical conditions such as transplantation, trauma, and hepatic failure after hemorrhagic shock. Apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. Ethyl pyruvate, a stable and simple lipophilic ester, has been shown to have anti-inflammatory properties. In this study, the purpose is to explore both the effect of ethyl pyruvate on hepatic I/R injury and regulation of intrinsic pathway of apoptosis and autophagy. Methods. Three doses of ethyl pyruvate (20 mg/kg, 40 mg/kg, and 80 mg/kg were administered 1 h before a model of segmental (70% hepatic warm ischemia was established in Balb/c mice. All serum and liver tissues were obtained at three different time points (4 h, 8 h, and 16 h. Results. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, and pathological features were significantly ameliorated by ethyl pyruvate (80 mg/kg. The expression of Bcl-2, Bax, Beclin-1, and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, was also obviously decreased by ethyl pyruvate (80 mg/kg. Furthermore, ethyl pyruvate inhibited the HMGB1/TLR4/ NF-κb axis and the release of cytokines (TNF-α and IL-6. Conclusion. Our results showed that ethyl pyruvate might attenuate to hepatic I/R injury by inhibiting intrinsic pathway of apoptosis and autophagy, mediated partly through downregulation of HMGB1/TLR4/ NF-κb axis and the competitive interaction with Beclin-1 of HMGB1.

  18. Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat

    International Nuclear Information System (INIS)

    Vikram, A.; Tripathi, D.N.; Ramarao, P.; Jena, G.B.

    2008-01-01

    Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic β-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the β-cells. The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level

  19. Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

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    Lubaczeuski, C.; Balbo, S.L.; Ribeiro, R.A.; Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M.; Bonfleur, M.L.

    2015-01-01

    The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca 2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca 2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats

  20. High Sucrose Intake Ameliorates the Accumulation of Hepatic Triacylglycerol Promoted by Restraint Stress in Young Rats.

    Science.gov (United States)

    Corona-Pérez, Adriana; Díaz-Muñoz, Mauricio; Rodríguez, Ida Soto; Cuevas, Estela; Martínez-Gómez, Margarita; Castelán, Francisco; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2015-11-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Stress promotes the onset of the NAFLD with a concomitant increment in the activity of the hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1). However, the interaction between the stress and a carbohydrate-enriched diet for the development of NAFLD in young animals is unknown. In the present study, we evaluated the impact of chronic stress on the hepatic triacylglycerol level of young rats fed or not with a high sucrose-diet. For doing this, 21-day old male Wistar rats were allocated into 4 groups: control (C), chronic restraint stress (St), high-sucrose diet (S30), and chronic restraint stress plus a 30 % sucrose diet (St + S30). Chronic restraint stress consisted of 1-hour daily session, 5 days per week and for 4 weeks. Rats were fed with a standard chow and tap water (C group) or 30 % sucrose diluted in water (S30 group). The St + S30 groups consumed less solid food but had an elevated visceral fat accumulation in comparison with the St group. The St group showed a high level of serum corticosterone and a high activity of the hepatic 11β-HSD-1 concomitantly to the augmentation of hepatic steatosis signs, a high hepatic triacylglycerol content, and hepatic oxidative stress. Conversely, the high-sucrose intake in stressed rats (St + S30 group) reduced the hepatic 11β-HSD-1 activity, the level of serum corticosterone, and the hepatic triacylglycerol content. Present findings show that a high-sucrose diet ameliorates the triacylglycerol accumulation in liver promoted by the restraint stress in young male rats.

  1. Amelioration of carbon tetrachloride-induced hepatic injury by emulsified Antrodia extract

    Directory of Open Access Journals (Sweden)

    Wei-Chih Chang

    2018-03-01

    Full Text Available Objective(s: Antrodia cinnamomea (AC is found with anti-inflammatory and immunomodulatory biological activities. In this study, we investigated the anti-hepatitis effect of the emulsified AC extract from RO water or supercritical fluid CO2 with ethanol co-solvent extract methods of AC preparations. Materials and Methods: Five groups of eight to ten weeks male rats with a count of ten for each group were studied to evaluate the protection of two kinds of AC extract from hepatic injury. Acute liver injury of rats was induced by injecting 40% carbon tetrachloride (CCl4 1 mg/kg intraperitoneally. Positive and negative control groups rats were perfused with CCl4 or isotonic saline, respectively. Experimental groups received oral administration once/day of AC preparations before CCl4 treatment: water AC extract (WAE group, or emulsified AC extract from supercritical fluid extraction (EAE group for 5 days, and sacrificed on the 6th day and the blood and liver samples were collected under chloral hydrate anesthesia. The anti-inflammatory, antioxidant markers, and relevant signaling pathways were measured (AST, ALT, ROS, IL-1, IL-6, NO, and COX-2, MAPKs, and caspase-3. Results: EAE at 50 mg/kg significantly decreased the serum AST, ALT, IL-1, IL-6, NO, and ROS levels. Both extracts reduced the activation of p-ERK in the liver samples, but EAE inhibited COX-2 and caspase-3 protein expression better than WAE. The EAE ameliorated CCl4-induced hepatic injury significantly; as compared with WAE and the positive control. Conclusion: The hepatoprotection of EAE could be attributed to the antioxidant and anti-inflammatory effects of Antrodia.

  2. Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

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    Lubaczeuski, C.; Balbo, S.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil); Ribeiro, R.A. [Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M. [Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP (Brazil); Bonfleur, M.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil)

    2015-02-24

    The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca{sup 2+} mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca{sup 2+} mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

  3. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  4. Topical KINOSTAT™ ameliorates the clinical development and progression of cataracts in dogs with diabetes mellitus.

    Science.gov (United States)

    Kador, Peter F; Webb, Terah R; Bras, Dineli; Ketring, Kerry; Wyman, Milton

    2010-11-01

    To determine whether topical administration of the aldose reductase inhibitor Kinostat™ can ameliorate the onset or progression of cataracts in dogs with naturally occurring diabetes mellitus (DM). A randomized, prospective, double-masked placebo control pilot study was conducted with 40 dogs newly diagnosed with DM with no or minimal lens changes. Twenty-eight dogs received Kinostat™ and 12 dogs received placebo. Owners administered the agent into both eyes three times daily for 1 year and compliance was monitored with log sheets. Complete ophthalmic examinations were performed on dilated eyes at the time of enrollment and 1, 2, 3, 6, and 12 months into treatment. Cataract severity was assessed on a scale of 0-3. At 12 months, full bloodwork, including HbA1C and blood Kinostat™ levels were performed. After 12 months of treatment, the cataract score in the placebo group significantly increased with seven dogs (14 eyes) developing mature cataracts, two dogs (4 eyes) developing cortical opacities, and one dog (2 eyes) developing equatorial vacuoles with mild punctate cortical opacities. In contrast, the cataract score in the Kinostat™ treated dogs was significantly less with seven developing anterior equatorial vacuoles, two developing incipient anterior cortical cataracts, and four developing mature cataracts. In fact, the cataract scores of the Kinostat™ group at 12 months did not significantly increase from the score at the time of enrollment. The HbA1C values between the two groups after 12 months of treatment were similar, and no blood levels of Kinostat™ were found in any enrolled dog. The onset and/or progression of cataracts in dogs with DM can be significantly delayed by topical administration of Kinostat™. © 2010 American College of Veterinary Ophthalmologists.

  5. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats

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    Tugba Yilmaz-Ozden

    2014-05-01

    Full Text Available Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight. Vanadyl sulfate (100 mg/kg body weight was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v homogenate. Catalase (CAT, superoxide dismutase (SOD, glutathione reductase (GR, glutathione peroxidase (GPx, glutathione-S-transferase (GST, myeloperoxidase (MPO, carbonic anhydrase (CA, glucose-6-phosphate dehydrogenase (G6PD and lactate dehydrogenase (LDH activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.

  6. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats.

    Science.gov (United States)

    Yilmaz-Ozden, Tugba; Kurt-Sirin, Ozlem; Tunali, Sevim; Akev, Nuriye; Can, Ayse; Yanardag, Refiye

    2014-05-01

    Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.

  7. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

    Science.gov (United States)

    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice.

    Science.gov (United States)

    Yamada, Marina; Hayashida, Miki; Zhao, Qi; Shibahara, Naotoshi; Tanaka, Ken; Miyata, Takeshi; Matsumoto, Kinzo

    2011-06-01

    Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M₁ receptor expression without affecting muscarinic M₃ receptor expression or AChE activity. These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Sulphate fertilization ameliorates long-term aluminum toxicity symptoms in perennial ryegrass (Lolium perenne).

    Science.gov (United States)

    Wulff-Zottele, Cristian; Hesse, Holger; Fisahn, Joachim; Bromke, Mariusz; Vera-Villalobos, Hernán; Li, Yan; Frenzel, Falko; Giavalisco, Patrick; Ribera-Fonseca, Alejandra; Zunino, Ligia; Caruso, Immcolata; Stohmann, Evelyn; Mora, Maria de la Luz

    2014-10-01

    Effects of the oxanion sulphate on plant aluminum (Al(3+)) detoxification mechanisms are not well understood. Therefore, holistic physiological and biochemical modifications induced by progressively increased doses of sulphate fertilization in the presence of long-term Al(3+) stress were investigated in the aluminum sensitive perennial ryegrass (Lolium perenne L. cvJumbo). Plant growth inhibition induced by Al(3+) was decreased in response to increasing doses of sulphate supply. Aluminum concentrations measured in roots of perennial ryegrass by atomic absorption spectrometry declined significantly with increasing sulphate concentrations. In parallel, we determined a rise of sulphur in shoots and roots of perennial ryegrass. Inclusion of up to 360 μM of sulphate enhanced cysteine and glutathione biosynthesis in Al(3+) (1.07 μM) treated plants. This increase of thiol-containing compounds favored all modifications in the glutathione redox balance, declining lipid peroxidation, decreasing the activity of superoxide dismutase, and modifying the expression of proteins involved in the diminution of Al(3+) toxicity in roots. In particular, proteome analysis by 1D-SDS-PAGE and LC-MS/MS allowed to identify up (e.g. vacuolar proton ATPase, proteosome β subunit, etc) and down (Glyoxilase I, Ascorbate peroxidase, etc.) regulated proteins induced by Al(3+) toxicity symptoms in roots. Although, sulphate supply up to 480 μM caused a reduction in Al(3+) toxicity symptoms, it was not as efficient as compared to 360 μM sulphate fertilization. These results suggest that sulphate fertilization ameliorates Al(3+) toxicity responses in an intracellular specific manner within Lolium perenne. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome.

    Science.gov (United States)

    Xiao, Shuiming; Fei, Na; Pang, Xiaoyan; Shen, Jian; Wang, Linghua; Zhang, Baorang; Zhang, Menghui; Zhang, Xiaojun; Zhang, Chenhong; Li, Min; Sun, Lifeng; Xue, Zhengsheng; Wang, Jingjing; Feng, Jie; Yan, Feiyan; Zhao, Naisi; Liu, Jiaqi; Long, Wenmin; Zhao, Liping

    2014-02-01

    Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes. © 2013 The Authors. FEMS Microbiology Ecology pubished by John Wiley & Sons Ltd on behalf of the Federation of European Microbiological Societies.

  11. Ameliorative effects of nano-elemental selenium against hexavalent chromium-induced apoptosis in broiler liver.

    Science.gov (United States)

    Xueting, Liu; Rehman, Mujeeb Ur; Mehmood, Khalid; Huang, Shucheng; Tian, Xinxin; Wu, Xiaoxing; Zhou, Donghai

    2018-03-23

    The current study examined the ameliorative effects of nano-elemental selenium (Nano-Se) against chromium-VI (K 2 Cr 2 O 7 )-induced apoptosis in chickens. The expression of apoptosis-related genes was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. A total of 60, one-day-old broiler chickens allotted to six equal groups, i.e., control group (standard diet), Cr(VI)-exposed group (K 2 Cr 2 O 7 via drinking water), Nano-Se group (Nano-Se at 0.5 mg/kg via diet), protection group (K 2 Cr 2 O 7  + Nano-Se), cure group (K 2 Cr 2 O 7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group) and were detected by the activities of pro-apoptosis (Bax, Caspase-3) and anti-apoptosis (Bcl-2) genes expression at day 35 of the experiment. Intense apoptosis was observed in liver tissues of chickens exposed to K 2 Cr 2 O 7 . The Nano-Se supplementation caused a significant decrease (P Nano-Se experimental groups as compare to control and Cr(VI)-exposed group. The results quantified by the RT-qPCR were further confirmed by the western blot analysis. Altogether, these results suggest anti-apoptotic effects of Nano-Se in the chicken liver, which is interesting for further study. The present findings suggested that Nano-Se has protective effects against K 2 Cr 2 O 7 -induced apoptosis in broilers liver and can serve a key role as a protective agent against apoptosis.

  12. Blockade of RAGE ameliorates elastase-induced emphysema development and progressionviaRAGE-DAMP signaling.

    Science.gov (United States)

    Lee, Hanbyeol; Park, Jeong-Ran; Kim, Woo Jin; Sundar, Isaac K; Rahman, Irfan; Park, Sung-Min; Yang, Se-Ran

    2017-05-01

    The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene for chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWASs). However, less is known about how RAGE is involved in the pathogenesis of COPD. To determine the molecular mechanism by which RAGE influences COPD in experimental COPD models, we investigated the efficacy of the RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD models. We injected elastase intratracheally and the RAGE antagonist FPS-ZM1 in mice, and the infiltrated inflammatory cells and cytokines were assessed by ELISA. Cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid of mice and lungs and serum of human donors and patients with COPD. Downstream damage-associated molecular pattern (DAMP) pathway activation in vivo and in vitro and in patients with COPD was assessed by immunofluorescence staining, Western blot analysis, and ELISA. The expression of membrane RAGE in initiating the inflammatory response and of soluble RAGE acting as a decoy were associated with up-regulation of the DAMP-related signaling pathway via Nrf2. FPS-ZM1 administration significantly reversed emphysema in the lung of mice. Moreover, FPS-ZM1 treatment significantly reduced lung inflammation in Nrf2 +/+ , but not in Nrf2 -/- mice. Thus, our data indicate for the first time that RAGE inhibition has an essential protective role in COPD. Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema/COPD.-Lee, H., Park, J.-R., Kim, W. J., Sundar, I. K., Rahman, I., Park, S.-M., Yang. S.-R. Blockade of RAGE ameliorates elastase-induced emphysema development and progression via RAGE-DAMP signaling. © FASEB.

  13. Ameliorative antimalarial effects of the combination of rutin and swertiamarin on malarial parasites

    Directory of Open Access Journals (Sweden)

    Divya Shitlani

    2016-06-01

    Full Text Available Objective: To ameliorate the antimalarial activity via the combination of rutin (flavonoid and swertiamarin (glycoside. Methods: The antimalarial effects were assessed by in vitro and in vivo methodology. In vitro antiplasmodial activity was assessed by using Plasmodium falciparum cultured media and determined the IC 50 value of individual drugs and their combinations. In in vivo methodology, antimalarial effects of rutin, swertiamarin (200–280 mg/kg/day, p.o. and their combination in 1:1, 1:2 and 2:1 ratios were investigated early and established malaria infections using Swiss albino mice infected with Plasmodium berghei. Chloroquine phosphate (5 mg/kg/day, p.o. was used as the standard drug. Results: IC 50 values of the rutin and swertiamarin via in vitro study revealed (9.50 ± 0.29 µg/ mL and (8.17 ± 0.17 µg/mL respectively. Whereas, the combination in 1:1 ratio [IC50 of (5.51 ± 0.18 µg/mL] showed better antiplasmodial activity against Plasmodium falciparum. In vivo results showed that rutin and swertiamarin had chemosuppressant effects in a dose-dependent manner, whereas, combination in 1:1 ratio possessed potential antimalarial activity similar to chloroquine phosphate. The drug interaction between rutin and swertiamarin revealed the synergistic effect on 1:1 ratio and additive effect on 1:2 and 2:1 ratios. Conclusions: The results of the in vitro and in vivo study clearly indicate that the combination (1:1 of rutin and swertiamarin showed potential antimalarial activity rather than an individual of each and their combinations 1:2 and 2:1.

  14. Docosahexaenoic Acid Ameliorates Fructose-Induced Hepatic Steatosis Involving ER Stress Response in Primary Mouse Hepatocytes

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    Jinying Zheng

    2016-01-01

    Full Text Available The increase in fructose consumption is considered to be a risk factor for developing nonalcoholic fatty liver disease (NAFLD. We investigated the effects of docosahexaenoic acid (DHA on hepatic lipid metabolism in fructose-treated primary mouse hepatocytes, and the changes of Endoplasmic reticulum (ER stress pathways in response to DHA treatment. The hepatocytes were treated with fructose, DHA, fructose plus DHA, tunicamycin (TM or fructose plus 4-phenylbutyric acid (PBA for 24 h. Intracellular triglyceride (TG accumulation was assessed by Oil Red O staining. The mRNA expression levels and protein levels related to lipid metabolism and ER stress response were determined by real-time PCR and Western blot. Fructose treatment led to obvious TG accumulation in primary hepatocytes through increasing expression of fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC, two key enzymes in hepatic de novo lipogenesis. DHA ameliorates fructose-induced TG accumulation by upregulating the expression of carnitine palmitoyltransferase 1A (CPT-1α and acyl-CoA oxidase 1 (ACOX1. DHA treatment or pretreatment with the ER stress inhibitor PBA significantly decreased TG accumulation and reduced the expression of glucose-regulated protein 78 (GRP78, total inositol-requiring kinase 1 (IRE1α and p-IRE1α. The present results suggest that DHA protects against high fructose-induced hepatocellular lipid accumulation. The current findings also suggest that alleviating the ER stress response seems to play a role in the prevention of fructose-induced hepatic steatosis by DHA.

  15. Family-centered prevention ameliorates the longitudinal association between risky family processes and epigenetic aging.

    Science.gov (United States)

    Brody, Gene H; Yu, Tianyi; Chen, Edith; Beach, Steven R H; Miller, Gregory E

    2016-05-01

    Research has suggested that 'risky' family processes have unforeseen negative consequences for health later in life. The purpose of this study was to further understanding of risky family environments and development of health vulnerabilities by (a) examining the likelihood that elevated levels of parental depressive symptoms when children are age 11 forecast accelerated epigenetic aging 9 years later at age 20; (b) determining whether participation in an efficacious family-centered prevention program focused on enhancing supportive parenting and strengthening family relationships will ameliorate this association; and (c) testing a moderation-mediation hypothesis that prevention-induced reductions in harsh parenting across adolescence will account for prevention effects in reducing accelerated epigenetic aging. In the rural southeastern United States, parents and 11-year-old children from 399 families participated in the Strong African American Families (SAAF) program or a control condition. Parents reported their own depressive symptoms when their children were 11, and both youths and parents reported youth exposure to harsh parenting at ages 11 and 16. Blood was drawn from youths at age 20 to measure accelerated epigenetic aging using a marker derived from the DNA methylation of cells. Elevated parental depressive symptoms forecast accelerated epigenetic aging among youths in the control condition, but not among SAAF participants. Moderated-mediation analyses confirmed that reductions in harsh parenting accounted for SAAF's protective effects on epigenetic aging. Subsequent exploratory analyses indicated that accelerated epigenetic aging forecast emotional distress among young adults in the control condition but not among those who participated in SAAF. This study is unique in using a randomized prevention trial to test hypotheses about the ways risky family processes contribute to accelerated epigenetic aging. The results suggest that developmentally

  16. The Impaired Function of Macrophages Induced by Strenuous Exercise Could Not Be Ameliorated by BCAA Supplementation

    Directory of Open Access Journals (Sweden)

    Weihua Xiao

    2015-10-01

    Full Text Available The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C Control, E Exercise, (E1 Exercise with one week to recover, (ES Exercise + Supplementation and (ES1 Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031, reactive oxygen species (ROS production (decreased by 26%, p = 0.003 and MHC II mRNA (decreased by 22%, p = 0.041 of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05. Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

  17. Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process.

    Science.gov (United States)

    Chen, Cheng; Wang, Yong-Yan; Wang, Ying-Xia; Cheng, Meng-Qun; Yin, Jian-Bing; Zhang, Xuan; Hong, Zhi-Peng

    2018-01-22

    Pulmonary fibrosis (PF) is a chronic and ultimately fatal interstitial lung disease of various causes. The advent of nintedanib and pirfenidone provides treatment options for PF patients for the first time. However, the adverse effects of the two drugs such as gastrointestinal disorders and hepatic dysfunction often lead to treatment discontinuation. Gentiopicroside (GPS) is a natural secoiridoid glycoside from gentian species of medicinal plants, and has a variety of pharmacological activities, including hepatoprotective and cholagogic, anti-inflammatory, antinociceptive, and smooth muscle relaxing activities. The present study aimed to investigate the therapeutical effects of GPS on bleomycin (BLM)-induced PF in mice. Severe lung inflammation and fibrosis were observed in BLM-treated mice. GPS significantly ameliorated inflammatory and fibrotic responses in lungs of PF mice which were confirmed by histopathological examinations including light microscopy and transmission electron microscopy. Additionally, GPS significantly decreased the levels of inflammatory cytokines including TNF-α and IL-1β in bronchoalveolar lavage fluid and reduced the content of hydroxyproline in lungs of PF mice. Furthermore, GPS significantly downregulated the expression of TGF-β1 and CTGF in lungs of PF mice. In vitro, GPS inhibited epithelial-mesenchymal transition of A549 cells stimulated by TGF-β1, in a dose-dependent manner. Our findings suggest that GPS has the potential as an ideal drug candidate for PF, as it has both anti-inflammatory and anti-fibrotic effects. Alveolar epithelial cells and TGF-β1 may be the main target cells and molecule of GPS on BLM-induced PF, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Amelioration of Heat-Stress Conditions of Egyptian Summer Season on Friesian Calves Using Air Condition

    International Nuclear Information System (INIS)

    Nessim, M.Z.; Kamal, T.H.; Khalil, W.K.B.

    2010-01-01

    Male Friesian calves were used to evaluate cool air condition (AC) in alleviating heat stress (HS) determined by Heat Shock Protein genes expression (HSP), hormonal, biochemical and physiological parameters. The animals were exposed to summer heat stress (HS) under shade for two weeks (control). The maximum temperature humidity index (THI) during summer HS was from 81 to 88. Afterward the animals were exposed to AC, inside a climatic chamber for 6 hours daily for two weeks, where, the THI was from 70 to 71. The results revealed that expression level of the Hsp genes (Hsp72, Hsp70.1, Hsp70 and Hsp47) was lower under air condition treatment than under summer heat stress. Rectal temperature and respiration rate were significantly lower (p< 0.01) under air condition treatment than those under heat stress. Total triiodothyronin (T3) level was significantly higher (P< 0.05) in AC cooling treatments than in HS, while cortisol level was significantly lower (P < 0.01) in AC cooling treatment than in HS calves. Creatinine and Urea -N levels were significantly lower (P < 0.01) in AC cooling treatment than in HS calves. Triglycerides, ALT and AST levels were significantly lower (p<0.01), (P< 0.01) and (p<0.05), respectively in AC cooling treatment than in HS calves. These results demonstrated that there is a relationship between the molecular weight of HSPs and the level of HSPs gene exprisson. The higher the molecular weight (HSP 72) the lower is the HSPs gene expression level (0.82 in HS and 0.39 in AC) and vise versa. This holds true in both heat stress and air condition. AC treatment is capable to ameliorate heat stress of Friesian calves under hot summer climate

  19. Chaperones ameliorate beta cell dysfunction associated with human islet amyloid polypeptide overexpression.

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    Lisa Cadavez

    Full Text Available In type 2 diabetes, beta-cell dysfunction is thought to be due to several causes, one being the formation of toxic protein aggregates called islet amyloid, formed by accumulations of misfolded human islet amyloid polypeptide (hIAPP. The process of hIAPP misfolding and aggregation is one of the factors that may activate the unfolded protein response (UPR, perturbing endoplasmic reticulum (ER homeostasis. Molecular chaperones have been described to be important in regulating ER response to ER stress. In the present work, we evaluate the role of chaperones in a stressed cellular model of hIAPP overexpression. A rat pancreatic beta-cell line expressing hIAPP exposed to thapsigargin or treated with high glucose and palmitic acid, both of which are known ER stress inducers, showed an increase in ER stress genes when compared to INS1E cells expressing rat IAPP or INS1E control cells. Treatment with molecular chaperone glucose-regulated protein 78 kDa (GRP78, also known as BiP or protein disulfite isomerase (PDI, and chemical chaperones taurine-conjugated ursodeoxycholic acid (TUDCA or 4-phenylbutyrate (PBA, alleviated ER stress and increased insulin secretion in hIAPP-expressing cells. Our results suggest that the overexpression of hIAPP induces a stronger response of ER stress markers. Moreover, endogenous and chemical chaperones are able to ameliorate induced ER stress and increase insulin secretion, suggesting that improving chaperone capacity can play an important role in improving beta-cell function in type 2 diabetes.

  20. N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

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    Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

    2017-01-01

    Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure

  1. Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats

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    Natarajan Ranganathan

    2005-01-01

    Full Text Available The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo-controlled pilot study, using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A Control, (B Placebo (casein-based diet without probiotics, (C Bacillus pasteurii, (D Sporolac®, (E Kibow cocktail, (F CHR Hansen Cocktail, and (G ECONORMTM. Subsequently, blood (retro-orbital and urine (collected for measurements of blood urea-nitrogen and creatinine respectively, body weight and bacterial counts (feces were obtained at regular intervals. The study end-points were to determine if any of the probiotic dietary supplements facilitated, (1 decreased blood concentrations of uremic toxins, (2 altered renal function, and (3 prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood urea-nitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure.

  2. Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

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    Bo Young Nam

    2017-06-01

    Full Text Available Peritoneal fibrosis is a major complication in peritoneal dialysis (PD patients, which leads to dialysis discontinuation. Periostin, increased by transforming growth factor β1 (TGF-β1 stimulation, induces the expression of extracellular matrix (ECM genes. Aberrant periostin expression has been demonstrated to be associated with PD-related peritoneal fibrosis. Therefore, the effect of periostin inhibition by an aptamer-based inhibitor on peritoneal fibrosis was evaluated. In vitro, TGF-β1 treatment upregulated periostin, fibronectin, α-smooth muscle actin (α-SMA, and Snail expression and reduced E-cadherin expression in human peritoneal mesothelial cells (HPMCs. Periostin small interfering RNA (siRNA treatment ameliorated the TGF-β1-induced periostin, fibronectin, α-SMA, and Snail expression and restored E-cadherin expression in HPMCs. Similarly, the periostin-binding DNA aptamer (PA also attenuated fibronectin, α-SMA, and Snail upregulation and E-cadherin downregulation in TGF-β1-stimulated HPMCs. In mice treated with PD solution for 4 weeks, the expression of periostin, fibronectin, α-SMA, and Snail was significantly increased in the peritoneum, whereas E-cadherin expression was significantly decreased. The thickness of the submesothelial layer and the intensity of Masson’s trichrome staining in the PD group were significantly increased compared to the untreated group. These changes were significantly abrogated by the intraperitoneal administration of PA. These findings suggest that PA can be a potential therapeutic strategy for peritoneal fibrosis in PD patients.

  3. Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats.

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    Chen, Chunxiu; Chen, Fengfeng; Yao, Chengye; Shu, Shaofang; Feng, Juan; Hu, Xiaoling; Hai, Quan; Yao, Shanglong; Chen, Xiangdong

    2016-12-01

    Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1β (IL-1β) and Interleukin -17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.

  4. Amelioration of meconium-induced acute lung injury by parecoxib in a rabbit model

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    Li, Ai-Min; Zhang, Li-Na; Li, Wen-Zhi

    2015-01-01

    Cyclooxygenase-2 (COX-2) plays important roles in various inflammatory conditions and is significantly increased in meconium-induced lung injury. We investigated the effects of parecoxib on meconium-induced acute lung injury (ALI) in rabbits. Twenty-four rabbits were randomized into sham, control, and parecoxib groups. Rabbits in the control and parecoxib groups underwent tracheal instillation of meconium, followed by intravenous injection of saline or parecoxib and 4 h of ventilation. The airway pressure, dynamic compliance, and ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2 ratio) were recorded at baseline (T0) and 4 h after instillation (T1-T4). The lung tissue wet-to-dry weight ratio; neutrophil percentage; and total protein, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-8, prostaglandin E2, and malondialdehyde levels in bronchoalveolar lavage fluid (BALF) were evaluated. The myeloperoxidase activity, COX-2 expression, and degree of histopathologic injury in lung tissue were also analyzed. The airway pressure, compliance, and PaO2/FiO2 ratio were significantly improved by parecoxib after meconium instillation. The lung wet-to-dry weight ratio, total protein level, and neutrophil percentage in BALF were lowest in the parecoxib group. The TNF-α, IL-1β, IL-8, prostaglandin E2, and malondialdehyde levels in the BALF were lowest in the parecoxib group. The COX-2 expression and myeloperoxidase activity in lung tissue were significantly reduced by parecoxib. The degree of lung injury was also reduced. In conclusions: Parecoxib effectively ameliorates respiratory function and attenuates meconium-induced ALI. These effects are correlated with prostaglandin E2 and COX-2 inhibition. PMID:26221218

  5. Treadmill exercise ameliorates symptoms of Alzheimer disease through suppressing microglial activation-induced apoptosis in rats.

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    Baek, Seung-Soo; Kim, Sang-Hoon

    2016-12-01

    Alzheimer disease (AD) is a most common form of dementia and eventually causes impairments of learning ability and memory function. In the present study, we investigated the effects of treadmill exercise on the symptoms of AD focusing on the microglial activation-induced apoptosis. AD was made by bilateral intracerebroventricular injection of streptozotocin. The rats in the exercise groups were made to run on a treadmill once a day for 30 min during 4 weeks. The distance and latency in the Morris water maze task and the latency in the step-down avoidance task were increased in the AD rats, in contrast, treadmill exercise shortened these parameters. The numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive and caspase-3-positive cells in the hippocampal dentate gyrus were decreased in the AD rats, in contrast, treadmill exercise suppressed these numbers. Expressions of glial fibrillary acidic protein (GFAP) and cluster of differentiation molecule 11B (CD11b) in the hippocampal dentate gyrus were increased in the AD rats, in contrast, treadmill exercise suppressed GFAP and CD11b expressions. Bax expression was increased and Bcl-2 expression was decreased in the hippocampus of AD rats, in contrast, treadmill exercise decreased Bax expression and increased Bcl-2 expression. The present results demonstrated that treadmill exercise ameliorated AD-induced impairments of spatial learning ability and short-term memory through suppressing apoptosis. The antiapoptotic effect of treadmill exercise might be ascribed to the inhibitory effect of treadmill exercise on microglial activation.

  6. Tinospora cordifolia consumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats.

    Science.gov (United States)

    Joladarashi, Darukeshwara; Chilkunda, Nandini D; Salimath, Paramahans V

    2012-01-01

    Diabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect of Tinospora cordifolia (TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containing TC at 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated in TC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in 'E' units and degree of sulphation were modulated in 5 % TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 % TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 and N-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of 'E' units which was reduced during diabetic condition, was significantly contained in the 5 % TC-fed group. Purified CS/DS from 5 % TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containing TC at the 5 % level modulates changes in kidney CS/DS which were due to diabetes.

  7. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

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    Chen, Han; Sun, Yan Ping; Li, Yang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Liu, Wen Wu [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xiang, Hong Gang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Fan, Lie Ying [Department of Clinical Laboratory, Shanghai East Hospital, Tong Ji University, Shanghai 200120 (China); Sun, Qiang [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xu, Xin Yun [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Cai, Jian Mei [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Ruan, Can Ping; Su, Ning; Yan, Rong Lin [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Sun, Xue Jun, E-mail: sunxjk@hotmail.com [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Wang, Qiang, E-mail: wang2929@hotmail.com [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  8. Blockade of the N-Methyl-D-Aspartate Glutamate Receptor Ameliorates Lipopolysaccharide-Induced Renal Insufficiency.

    Science.gov (United States)

    Lin, Chian-Shiung; Hung, Shun-Fa; Huang, Ho-Shiang; Ma, Ming-Chieh

    2015-01-01

    N-methyl-D-aspartate (NMDA) receptor activation in rat kidney reduces renal perfusion and ultrafiltration. Hypoperfusion-induced ischemia is the most frequent cause of functional insufficiency in the endotoxemic kidney. Here, we used non-hypotensive rat model of lipopolysaccharide-induced endotoxemia to examine whether NMDA receptor hyperfunction contributes to acute kidney injury. Lipopolysaccharide-induced renal damage via increased enzymuria and hemodynamic impairments were ameliorated by co-treatment with the NMDA receptor blocker, MK-801. The NMDA receptor NR1 subunit in the rat kidney mainly co-localized with serine racemase, an enzyme responsible for synthesizing the NMDA receptor co-agonist, D-serine. The NMDA receptor hyperfunction in lipopolysaccharide-treated kidneys was demonstrated by NR1 and serine racemase upregulation, particularly in renal tubules, and by increased D-serine levels. Lipopolysaccharide also induced cell damage in cultured tubular cell lines and primary rat proximal tubular cells. This damage was mitigated by MK-801 and by small interfering RNA targeting NR1. Lipopolysaccharide increased cytokine release in tubular cell lines via toll-like receptor 4. The release of interleukin-1β from these cells are the most abundant. An interleukin-1 receptor antagonist not only attenuated cell death but also abolished lipopolysaccharide-induced NR1 and serine racemase upregulation and increases in D-serine secretion, suggesting that interleukin-1β-mediated NMDA receptor hyperfunction participates in lipopolysaccharide-induced tubular damage. The results of this study indicate NMDA receptor hyperfunction via cytokine effect participates in lipopolysaccharide-induced renal insufficiency. Blockade of NMDA receptors may represent a promising therapeutic strategy for the treatment of sepsis-associated renal failure.

  9. Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.

    Science.gov (United States)

    Nakamura, Masuo; Wada, Hiroo; Honda, Kojiro; Nakamoto, Keitaro; Inui, Toshiya; Sada, Mitsuru; Watanabe, Masato; Takata, Saori; Yokoyama, Takuma; Saraya, Takeshi; Kurai, Daisuke; Ishii, Haruyuki; Goto, Hajime; Kamma, Hiroshi; Takizawa, Hajime

    2015-12-01

    Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    Science.gov (United States)

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Abdelaziz, Dalia H A; Ali, Sahar A; Mostafa, Mahmoud M A

    2015-06-01

    In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored. The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats. The aqueous suspension of P. dactylifera seeds (aqPDS) (1 g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase. Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248 ± 42 versus 508 ± 60 mg/dl), urea (32 ± 3.3 versus 48.3 ± 5.6 mg/dl), creatinine (2.2 ± 0.35 versus 3.8 ± 0.37 mg/dl), ALT (29.6 ± 3.9 versus 46.4 ± 5.9 IU/l), and AST (73.3 ± 13 versus 127.8 ± 18.7 IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats. The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.

  12. In vivo neutralization of IL-6 receptors ameliorates gastrointestinal dysfunction in dystrophin-deficient mdx mice.

    Science.gov (United States)

    Manning, J; Buckley, M M; O'Halloran, K D; O'Malley, D

    2016-07-01

    Duchenne muscular dystrophy (DMD) is a fatal disease characterized by progressive deterioration and degeneration of striated muscle. A mutation resulting in the loss of dystrophin, a structural protein which protects cells from contraction-induced damage, underlies DMD pathophysiology. Damage to muscle fibers results in chronic inflammation and elevated levels of proinflammatory cytokines such as interleukin-6 (IL-6). However, loss of cellular dystrophin also affects neurons and smooth muscle in the gastrointestinal (GI) tract with complaints such as hypomotility, pseudo-obstruction, and constipation reported in DMD patients. Using dystrophin-deficient mdx mice, studies were carried out to examine colonic morphology and function compared with wild-type mice. Treatment with neutralizing IL-6 receptor antibodies (xIL-6R) and/or the corticotropin-releasing factor (CRF) 2 receptor agonist, urocortin 2 (uro2) was tested to determine if they ameliorated GI dysfunction in mdx mice. Mdx mice exhibited thickening of colonic smooth muscle layers and delayed stress-induced defecation. In organ bath studies, neurally mediated IL-6-evoked contractions were larger in mdx colons. In vivo treatment of mdx mice with xIL-6R normalized defecation rates and colon lengths. Uro2 treatment did not affect motility or morphology. The potentiated colonic contractile response to IL-6 was attenuated by treatment with xIL-6R. These findings confirm the importance of dystrophin in normal GI function and implicate IL-6 as an important regulator of GI motility in the mdx mouse. Inhibition of IL-6 signaling may offer a potential new therapeutic strategy for treating DMD-associated GI symptoms. © 2016 John Wiley & Sons Ltd.

  13. Silencing miR-146a influences B cells and ameliorates experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Zhang, JunMei; Jia, Ge; Liu, Qun; Hu, Jue; Yan, Mei; Yang, BaiFeng; Yang, Huan; Zhou, WenBin; Li, Jing

    2015-01-01

    MicroRNAs have been shown to be important regulators of immune homeostasis as patients with aberrant microRNA expression appeared to be more susceptible to autoimmune diseases. We recently found that miR-146a was up-regulated in activated B cells in response to rat acetylcholine receptor (AChR) α-subunit 97-116 peptide, and this up-regulation was significantly attenuated by AntagomiR-146a. Our data also demonstrated that silencing miR-146a with its inhibitor AntagomiR-146a effectively ameliorated clinical myasthenic symptoms in mice with ongoing experimental autoimmune myasthenia gravis. Furthermore, multiple defects were observed after miR-146a was knocked down in B cells, including decreased anti-R97-116 antibody production and class switching, reduced numbers of plasma cells, memory B cells and B-1 cells, and weakened activation of B cells. Previously, miR-146a has been identified as a nuclear factor-κB-dependent gene and predicted to base pair with the tumour necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1) genes to regulate the immune response. However, our study proved that miR-146a inhibition had no effect on the expression of TRAF6 and IRAK1 in B cells. This result suggests that the function of miR-146a in B cells does not involve these two target molecules. We conclude that silencing miR-146a exerts its therapeutic effects by influencing the B-cell functions that contribute to the autoimmune pathogenesis of myasthenia gravis. © 2014 John Wiley & Sons Ltd.

  14. Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies.

    Science.gov (United States)

    Briffa, Michelle; Ghio, Stephanie; Neuner, Johanna; Gauci, Alison J; Cacciottolo, Rebecca; Marchal, Christelle; Caruana, Mario; Cullin, Christophe; Vassallo, Neville; Cauchi, Ruben J

    2017-01-18

    A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities. In the present report, we investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviate neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD. Pre-treatment with EPP or EOFI in the culture medium significantly improved the viability of yeast expressing the Arctic Aβ42 (E22G) mutant. Supplementing food with EOFI or EPP dramatically ameliorated lifespan and behavioural signs of flies with brain-specific expression of wild-type Aβ42 (model of late-onset AD) or the Arctic Aβ42 variant (model of early-onset AD). Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn A53T mutant. Taken together, our findings suggest that the plant-derived extracts interfere with shared mechanisms of neurodegeneration in AD and PD. This notion is strengthened by evidence demonstrating that EOFI and to a greater extent EPP, while strongly inhibiting the fibrillogenesis of both Aβ42 and α-syn, accumulate remodelled oligomeric aggregates that are less effective at disrupting lipid membrane integrity. Our work therefore opens new avenues for developing therapeutic applications of these natural plant extracts in the treatment of amyloidogenic

  15. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

    Directory of Open Access Journals (Sweden)

    Xiaodi Yang

    Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

  16. Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock.

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    Wang, Hao; Guan, Yuxia; Widlund, Anne Lykkegaard; Becker, Lance B; Baur, Joseph A; Reilly, Patrick M; Sims, Carrie A

    2014-12-01

    Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model Assessment-Insulin Resistance index was used to quantify insulin resistance. RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 ± 8.3 mg/dL, p GLP-1 levels (385.8 ± 56.6 ng/mL vs. 187.3 ± 11.1 ng/mL, p effect on plasma corticosterone, glucagon, or cytokine levels. Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion.

  17. Mitochondrial dysfunction in H9c2 cells during ischemia and amelioration with Tribulus terrestris L.

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    Reshma, P L; Sainu, Neethu S; Mathew, Anil K; Raghu, K G

    2016-05-01

    The present study investigates the protective effect of partially characterized Tribulus terrestris L. fruit methanol extract against mitochondrial dysfunction in cell based (H9c2) myocardial ischemia model. To induce ischemia, the cells were maintained in an ischemic buffer (composition in mM -137 NaCl, 12 KCl, 0.5 MgCl2, 0.9 CaCl2, 20 HEPES, 20 2-deoxy-d-glucose, pH-6.2) at 37°C with 0.1% O2, 5% CO2, and 95% N2 in a hypoxia incubator for 1h. Cells were pretreated with various concentrations of T. terrestris L. fruit methanol extract (10 and 25μg/ml) and Cyclosporin A (1μM) for 24h prior to the induction of ischemia. Different parameters like lactate dehydrogenase release, total antioxidant capacity, glutathione content and antioxidant enzymes were investigated. Studies were conducted on mitochondria by analyzing alterations in mitochondrial membrane potential, integrity, and dynamics (fission and fusion proteins - Mfn1, Mfn2, OPA1, Drp1 and Fis1). Various biochemical processes in mitochondria like activity of electron transport chain (ETC) complexes, oxygen consumption and ATP production was measured. Ischemia for 1h caused a significant (p≤0.05) increase in LDH leakage, decrease in antioxidant activity and caused mitochondrial dysfunction. T. terrestris L. fruit methanol extract pretreatment was found effective in safeguarding mitochondria via its antioxidant potential, mediated through various bioactives. HPLC of T. terrestris L. fruit methanol extract revealed the presence of ferulic acid, phloridzin and diosgenin. T. terrestris L. fruit ameliorate ischemic insult in H9c2 cells by safeguarding mitochondrial function. This validates the use of T. terrestris L. against heart disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse.

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    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. The fruit extract of TT ameliorates the MTZ-induced alterations in the testis.

  19. Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice

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    Yukihiro Horie

    2013-01-01

    Full Text Available Acute ultraviolet (UV B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice. C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse and UVB-exposed (400 mJ/cm2, GGA-untreated UVB-exposed (400 mJ/cm2, GGA-treated (500 mg/kg/mouse but not exposed and naive controls. Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H&E and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL. HSP70, reactive oxygen species (ROS production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and protein kinase B (Akt expression were also evaluated. Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0.01. Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0.01. Corneal HSP70 levels were significantly elevated in corneas of mice treated with GGA (p < 0.05. ROS signal was not affected by GGA. NF-κB activation was reduced but phospho-(Ser/Ther Akt substrate expression was increased in corneas after irradiation when treated with GGA. GGA-treatment induced HSP70 expression and ameliorated UV-induced corneal damage through the reduced NF-κB activation and possibly increased Akt phosphorilation.

  20. Aronia Berry Extract Ameliorates the Severity of Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

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    Kang, Sa-Haeng; Jeon, Yong-Deok; Moon, Kwang-Hyun; Lee, Jeong-Ho; Kim, Dae-Geun; Kim, Wook; Myung, Hyun; Kim, Jong-Sung; Kim, Hyun-Ju; Bang, Keuk-Soo; Jin, Jong-Sik

    2017-07-01

    Inflammatory bowel disease, including Crohn's disease and ulcerative colitis (UC), is a group of inflammatory conditions of the colon and small intestine. UC is a chronic inflammatory disorder of the colon and rectum that includes intervals of acute exacerbation. Although recent studies have suggested that proinflammatory cytokines might have initiated the inflammatory responses in UC, its etiology remains unclear. Aronia berries are rich in dietary polyphenols such as phenolic acids, anthocyanins, flavonoids, and proanthocyanidins with various health benefits, including antioxidant, anti-inflammatory, and antiaging activities. The objective of this study was to determine whether Aronia berry can be an effective intervention for the treatment of UC. BALB/c mice were administered 5% dextran sulfate sodium (DSS) to induce UC. They were then given Aronia berry extracts at concentrations of 10 or 100 mg/kg. During the induction of UC, the expression levels of nuclear factor-kappa B were increased in colonic epithelial cells and immune cells, leading to increased proinflammatory cytokine levels. Aronia berry extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. Furthermore, oral administration of Aronia berry extract inhibited prostaglandin E 2 production in DSS-induced colitis and decreased the levels of nitric oxide, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated macrophages. These results suggest that Aronia berry extract could efficiently ameliorate clinical signs and inflammatory mediators of UC. Therefore, Aronia berry might be a promising natural treatment for UC.

  1. Ameliorant Application on Variation of Carbon Stock and Ash Content on Peatland South Kalimantan

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    Siti Nurzakiah

    2013-03-01

    Full Text Available Carbon stock on peatlands are large and will be easily emitted if the land is opened or drained, therefore the measurements of carbon stocks and ash content are important to know the amount of emissions and agricultural sustainability in peatlands. This study aimed to determine carbon stock and ash content on peatlands in the Indonesia Climate Change Trust Fund (ICCTF located in South Kalimantan on the geographic position S. 03°25’52" and E. 114°47’6.5". The experiment consisted of six treatments of ameliorant materials namely; mineral soil, peat fertilizer A, peat fertilizer T, manure, ash, and control. The results showed that the variation of peat soil properties was very high at this location. Peat thickness ranged from 36-338 cm, and this led to high variations in carbon stocks ranged between 161.8 – 1142.2 Mg ha-1. Besides ash contents of the soil were also highly varied ranged from 3.4 – 28.5%. This natural variation greatly affected the ICCTF study design. Mineral soil treatment had a mean carbon stock (961.3 ± 61.5 Mg ha-1 which was higher and different from other treatments. High ash content was obtained in the ash treatment (18.6 ± 2.5% and manure (15.7 ± 3.6%. It is recommended that the analysis of plant responses and greenhouse gas emissions using a single regression analysis and multiple regression with ash content as one of the independent variables are needed.

  2. BAFF Receptor mAb Treatment Ameliorates Development and Progression of Atherosclerosis in Hyperlipidemic ApoE−/− Mice

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    Kyaw, Tin; Cui, Peng; Tay, Christopher; Kanellakis, Peter; Hosseini, Hamid; Liu, Edgar; Rolink, Antonius G.; Tipping, Peter

    2013-01-01

    Aims Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE−/− mouse. Methods and Results To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE−/− mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93− CD19+ B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19+ B cells, CD4+ and CD8+ T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1β, TNFα, and IFNγ in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE−/− mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93− CD19+ B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. Conclusion Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE−/− mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases. PMID:23560095

  3. The mixture of procyanidins extracted from the lotus seed pod and bilobalide ameliorates scopolamine-induced memory impairment in mice.

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    Zhang, Li; Xu, Ji-Qu; Rong, Shuang; Xie, Bi-Jun; Sun, Zhi-Da; Zhang, Yun-Jian; Liu, Lie-Gang

    2009-08-01

    To study the co-effect of procyanidins extracted from the lotus seed pod (LSPC) and bilobalide (BIL) on ameliorating scopolamine-induced learning and memory impairment in young mice. Fifty male Kunming mice with similar learning and memory capabilities were selected by Morris water maze test and were randomized into 5 groups (n=10 in each group): control group, scopolamine group, L-(LSPC+BIL) group (50 mg/kg LSPC+10 mg/kg BIL), M-(LSPC+BIL) group (100 mg/kg LSPC+20 mg/kg BIL), H-(LSPC+BIL) group (150 mg/kg LSPC+30 mg/kg BIL). Scopolamine model with impaired learning and memory was established by scopolamine treatment (1 mg/kg), and after 10 min mice were tested. In L-, M-, and H-(LSPC+BIL) groups, mice were treated with LSPC and BIL ig. for 30 days, while mice in the other 2 groups were treated with normal saline ig. instead. After the 30-day's treatment, the co-effect of LSPC and BIL on learning and memory was tested by Morris water maze and the step-down avoidance tests. The memory impairment caused by scopolamine in young mice could be ameliorated by co-treatment of LSPC and BIL, as indicated by significantly shorter escape latency and swimming distance in the Morris water maze test, when compared with those in the scopolamine group. In the step-down avoidance test, mice in all the 3 dose groups showed significantly smaller number of errors and longer latency than mice in the scopolamine group did. Co-treatment of LSPE and BIL can ameliorate scopolamine-induced learning and memory impairment in young mice.

  4. BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE(-/- mice.

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    Tin Kyaw

    Full Text Available AIMS: Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE(-/- mouse. METHODS AND RESULTS: To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE(-/- mice with the antibody while feeding them a high fat diet (HFD for 8 weeks. Mature CD93(- CD19(+ B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19(+ B cells, CD4(+ and CD8(+ T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1β, TNFα, and IFNγ in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE(-/- mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93(- CD19(+ B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. CONCLUSION: Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE(-/- mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases.

  5. The chaperone activity of 4PBA ameliorates the skeletal phenotype of Chihuahua, a zebrafish model for dominant osteogenesis imperfecta.

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    Gioia, Roberta; Tonelli, Francesca; Ceppi, Ilaria; Biggiogera, Marco; Leikin, Sergey; Fisher, Shannon; Tenedini, Elena; Yorgan, Timur A; Schinke, Thorsten; Tian, Kun; Schwartz, Jean-Marc; Forte, Fabiana; Wagener, Raimund; Villani, Simona; Rossi, Antonio; Forlino, Antonella

    2017-08-01

    Classical osteogenesis imperfecta (OI) is a bone disease caused by type I collagen mutations and characterized by bone fragility, frequent fractures in absence of trauma and growth deficiency. No definitive cure is available for OI and to develop novel drug therapies, taking advantage of a repositioning strategy, the small teleost zebrafish (Danio rerio) is a particularly appealing model. Its small size, high proliferative rate, embryo transparency and small amount of drug required make zebrafish the model of choice for drug screening studies, when a valid disease model is available. We performed a deep characterization of the zebrafish mutant Chihuahua, that carries a G574D (p.G736D) substitution in the α1 chain of type I collagen. We successfully validated it as a model for classical OI. Growth of mutants was delayed compared with WT. X-ray, µCT, alizarin red/alcian blue and calcein staining revealed severe skeletal deformity, presence of fractures and delayed mineralization. Type I collagen extracted from different tissues showed abnormal electrophoretic migration and low melting temperature. The presence of endoplasmic reticulum (ER) enlargement due to mutant collagen retention in osteoblasts and fibroblasts of mutant fish was shown by electron and confocal microscopy. Two chemical chaperones, 4PBA and TUDCA, were used to ameliorate the cellular stress and indeed 4PBA ameliorated bone mineralization in larvae and skeletal deformities in adult, mainly acting on reducing ER cisternae size and favoring collagen secretion. In conclusion, our data demonstrated that ER stress is a novel target to ameliorate OI phenotype; chemical chaperones such as 4PBA may be, alone or in combination, a new class of molecules to be further investigated for OI treatment. © The Author 2017. Published by Oxford University Press.

  6. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat.

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    Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

    2015-01-01

    Baicalin belongs to glucuronic acid glycosides and after hydrolysis baicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat.

  7. PARTIALLY HYDROLYZED GUAR GUM INTAKE AMELIORATES CONSTIPATION, IMPROVES NUTRITIONAL STATUS AND REDUCES INDOXYLSULFURIC ACID IN DIALYSIS PATIENTS.

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    Hiroto Maeda

    2012-06-01

    Full Text Available Dialysis patients often develop constipation and changes in intestinal bacterial flora. Indoxylsulfuric acid (IS levels rise as glomerular filtration decreases, and patients with renal failure have high IS. Elevated IS is also caused by increased indole due to altered intestinal flora (Takayama et al, Am J Kidney Dis. 2003. We investigated whether administering partially hydrolyzed guar gum (PHGG (Sunfiber: a product of Taiyokagaku Co., Ltd., Japan ameliorates constipation and improves nutritional status in dialysis patients, while decreasing IS levels. Thirty-five patients on maintenance dialysis (mean age, 71 ± 9; male/female= 22/13 ingested PHGG (10 g/day for 6 weeks. Defecation was scored before and after PHGG intake using a modified Constipation Assessment Scale-Long Term (Japanese version. Nutritional status was rated according to the Geriatric Nutritional Risk Index (GNRI before and after PHGG intake. IS was measured in 8 patients taking PHGG orally for 24 weeks, for comparison with those in 8 patients not on PHGG. Constipation scores decreased from 7.9 to 5.0 (p 〈.01 and GNRI increased from 95.0 ± 5.0 to 95.9 ± 5.7 (p 〈.05, reflecting amelioration of constipation and improved nutritional status. The ratio of IS after to that before PHGG intake was calculated to analyze the magnitude of IS change. The ratio in patients not on PHGG was 1.2 ± 0.3, i.e. IS rose, while that in patients taking PHGG was significantly reduced (0.8 ± 0.3, p 〈.05. Our results indicate PHGG consumption to ameliorate constipation and improve nutritional status, and that continued intake reduces IS, in dialysis patients.

  8. Pu-erh Tea Extract Ameliorates Ovariectomy-Induced Osteoporosis in Rats and Suppresses Osteoclastogenesis In Vitro

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    Titi Liu

    2017-05-01

    Full Text Available Background and Objective: Tea drinking is associated with positive effects on bone health and may protect against osteoporosis, especially in elderly women. Pu-erh tea has many beneficial effects on human health; however, whether Pu-erh tea has anti-osteoporotic potential remains unclear. Thus, we investigated the effects of Pu-erh tea extract (PTE on ovariectomy-induced osteoporosis in rats and on osteoclastogenesis in vitro.Methods: Female Wistar rats were divided into six groups: the sham, model, and Xian-Ling-Gu-Bao capsule (XLGB groups, and the low-, medium-, and high-dose PTE groups. Ovariectomized (OVX rats were used as an animal model of osteoporosis. The animals were intragastrically administered distilled water, XLGB, or different concentrations of PTE for 13 weeks. Body weight, blood biochemical indicators, relative organ coefficients, femoral bone mineral density (BMD, bone biomechanical properties, and bone microarchitecture were examined and analyzed. Additionally, the in vitro effects of PTE on osteoclastic activities were investigated using the RAW 264.7 cell line as an osteoclast differentiation model. The effects of PTE on osteoclast differentiation and the expression of osteoclast-specific genes and proteins were determined.Results: PTE reduced OVX-induced body weight gain after 6 weeks of treatment, and the high-dose exerted a significant effect. High-dose PTE significantly ameliorated OVX-induced estradiol (E2 deficiency. PTE treatment maintained calcium and phosphorus homeostasis and improved other blood biochemical parameters to various degrees. In addition, PTE treatment improved organ coefficients of the femur, uterus, and vagina and improved femoral BMD and bone biomechanical properties. PTE treatment strikingly ameliorated bone microarchitecture. Moreover, in the in vitro studies, osteoclast differentiation using the differentiation cell model was significantly inhibited by PTE without cytotoxic effects. Additionally

  9. Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats.

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    Adaramoye, Oluwatosin A; Adedara, Isaac A; Farombi, E Olatunde

    2012-05-01

    Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body γ-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of γ-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to γ-radiation. Gamma-irradiation resulted in a significant (pin body weight and relative testes weight. Also, γ-irradiation significantly (pin the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (prats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together, γ-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity. Copyright © 2010 Elsevier GmbH. All rights reserved.

  10. Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction.

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    Shindo, T