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Sample records for alpha lipoic acid

  1. Synthesis and anticancer evaluation of alpha-lipoic acid derivatives.

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    Zhang, Shi-Jie; Ge, Qiu-Fu; Guo, Dian-Wu; Hu, Wei-Xiao; Liu, Hua-Zhang

    2010-05-15

    alpha-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 microg/mL. Compound 17 m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which had 24.7% tumor-weight inhibition through intragastric administration of 200mg/kg of body weight. Moreover, the LD(50) in mice for 17 m through ig exceeded 1000 mg/kg of body weight.

  2. Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

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    Hadzik, B; Grass, H; Mayatepek, E; Daldrup, T; Hoehn, T

    2014-09-01

    The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

  3. Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.

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    Melli, Giorgia; Taiana, Michela; Camozzi, Francesca; Triolo, Daniela; Podini, Paola; Quattrini, Angelo; Taroni, Franco; Lauria, Giuseppe

    2008-12-01

    The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.

  4. The Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension

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    Sharon L. H. Ong

    2013-01-01

    Full Text Available Aims. To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT and dexamethasone-induced hypertensions (DEX-HT in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition. Methods. In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day, or dexamethasone (DEX, 10 μg/rat/day was injected subcutaneously from day 5 to day 11. In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff systolic blood pressure (SBP was measured second daily. Kidney mitochondrial superoxide was examined using (MitoSOX Red (MitoSOX via flow cytometry. Results. SBP was increased by ACTH (P<0.0005 and DEX (P<0.0005. Alpha-lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P′<0.005 but not by DEX. Alpha-lipoic partially prevented ACTH-HT (P′<0.0005 and fully prevented DEX-HT (P′<0.0005 but failed to reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day did not decrease SBP further but raised MitoSOX signal (P<0.001, suggesting prooxidant activity. Conclusion. Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.

  5. Dietary alpha-Lipoic Acid Alters Piglet Neurodevelopment

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    Austin T Mudd

    2016-05-01

    Full Text Available Introduction: Alpha-lipoic acid (a-LA is an antioxidant shown to ameliorate age-associated impairments of brain and cardiovascular function. Human milk is known to have high antioxidant capacity, however the role of antioxidants in the developing brain is largely uncharacterized. This exploratory study aimed to examine the dose response effects of a-LA on piglet growth and neurodevelopment. Methods: Beginning at 2 d of age, 31 male pigs received one of three diets: control (CONT [0 mg a-LA/100g], low a-LA (LOW [120 mg a-LA/100g], or high a-LA (HIGH [240 mg a-LA/100g]. From 14 to 28 d of age, pigs were subjected to spatial T-maze assessment and macrostructural and microstructural neuroimaging procedures were performed at 31 d of age.Results: No differences due to diet were observed for bodyweight gain or intestinal weight and length. Spatial T-maze assessment did not reveal learning differences due to diet in proportion of correct choices or latency to choice measures. Diffusion tensor imaging revealed decreased (P = 0.01 fractional anisotropy (FA in the internal capsule of HIGH fed pigs compared with both the CONT (P < 0.01 and LOW (P = 0.03 fed pigs, which were not different from one another. Analysis of axial diffusivity (AD within the internal capsule revealed a main effect of diet (P < 0.01 in which HIGH fed piglets exhibited smaller (P < 0.01 rates of diffusion compared with CONT piglets, but HIGH fed piglets were not different (P = 0.12 than LOW fed piglets. Tract-based spatial statistics, a comparison of FA values along white matter tracts, revealed 1,650 voxels where CONT piglets exhibited higher (P < 0.05 values compared with HIGH fed piglets. Conclusion: The lack of differences in intestinal and bodyweight measures among piglets indicate a-LA supplementation does not impact overall growth, regardless of concentration. Additionally, no observed differences between CONT and LOW fed piglets in behavior and neuroimaging measures indicate a

  6. Biological properties of lipoic acid

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    Anna Bilska

    2002-06-01

    Full Text Available Lipoic acid is a prostetic group of H-protein of the glycine cleavage system and the dihydrolipoamide acyltransferases (E2 of the pyruvate, alpha-ketoglutarate and branched-chain alpha-keto acid dehydrogenase complexes. Lipoic acid and its reduced form, dihydrolipoic acid, reacts with oxygen reactive species. This paper reviews the beneficial effects in oxidative stress models or clinical conditions.

  7. Effects of alpha-lipoic acids on sperm membrane integrity during liquid storage of boar semen

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    Laura Parlapan

    2015-05-01

    Full Text Available Preliminary studies have shown that sperm membrane from swine shows high sensitivity to cryopreservation process, causing a dramatic reduction in sperm quality. This has been attributed to the production of reactive oxygen species, that cause lipid peroxidation in sperm membranes. The aim of the present study was to minimize the oxidative attack by adding different concentration of alpha-lipoic acid into the sperm liquid storage at 17ºC for 7 days. Freshly ejaculated boar semen was diluted with Beltsville Thawing Solution (BTS and supplemented with 5 levels of alpha-lipoic  acid (0.015, 0.02, 0.05, 0.1, 0.15 mmol/ml. The membrane integrity was evaluated at days 0, 1, 3, 5 and 7 of liquid preservation, using flow cytometer FACSCanto II (BD Biociencias systems. The experiment indicate that supplementation of alpha-lipoic  acid to the semen liquid storage extender improve sperm membrane

  8. Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.

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    Mahmoud, Y I; Hegazy, H G

    2016-01-01

    Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.

  9. The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

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    Ahmet Ali Tuncer

    2016-01-01

    Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

  10. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease.

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    Shinto, Lynne; Quinn, Joseph; Montine, Thomas; Dodge, Hiroko H; Woodward, William; Baldauf-Wagner, Sara; Waichunas, Dana; Bumgarner, Lauren; Bourdette, Dennis; Silbert, Lisa; Kaye, Jeffrey

    2014-01-01

    Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 + LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3 + LA showed less decline in MMSE (p omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted.

  11. Effect of Alpha-lipoic Acid Supplementation on Serum Lipid Profile in Women with Rheumatoid Arthritis

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    Elham Mirtaheri

    2014-09-01

    Conclusions: In the present study, serum lipid profile was not significantly affected by ALA intervention. However, ALA supplementation aiming at prevention or treatment of dyslipidemia in RA patients should be further investigated. Keywords: Lipoic acid, Supplementation, Rheumatoid arthritis, Women, Lipid profile

  12. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

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    Turamanlar, Ozan; Özen, Oğuz Aslan; Songur, Ahmet; Yağmurca, Murat; Akçer, Sezer; Mollaoğlu, Hakan; Aktaş, Cevat

    2015-01-01

    Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250–300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were

  13. Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?

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    Seybolt, Sheila E J

    2010-12-01

    As sulfur containing thiols, alpha lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants and free radical scavengers capable of performing many of the same functions as glutathione (GSH). ALA supplementation may help protect mitochondria from oxidative stress, a possible mechanism contributing to certain forms of brain diseases called schizophrenia. Shortly before the advent of antipsychotic medications, two small studies found ALA relieved psychiatric symptoms in schizophrenia. More recently, animal studies have shown ALA augmentation improves mitochondrial function. At pharmaceutical levels, niacinamide helps preserve mitochondrial membrane integrity and acts as an antioxidant. ALA is a precursor for lipoamide, an essential mitochondrial coenzyme and niacinamide is a component of niacinamide adenine dinucleotide (NAD). NADH, the reduced form of NAD, is involved in the reduction of ALA to DHLA within the mitochondria. This is relevant to contemporary research because DHLA increases GSH and low GSH levels contribute to mitochondrial dysfunction and oxidative stress which have been implicated in the pathophysiology of schizophrenia.

  14. Protective effects of alpha lipoic acid versus N-acetylcysteine on ifosfamide-induced nephrotoxicity.

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    El-Sisi, Alaa El-Din E; El-Syaad, Magda E; El-Desoky, Karima I; Moussa, Ethar A

    2015-02-01

    Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors. However, its use is limited due to its serious side effect on kidneys. The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect. Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity. Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days). Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined. Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO. NAC was more nephroprotective than ALA. This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats. The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.

  15. The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity.

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    Asci, Halil; Saygin, Mustafa; Cankara, Fatma Nihan; Bayram, Dilek; Yesilot, Sukriye; Candan, Ibrahim Aydin; Ilhan, Ilter

    2015-02-01

    Amikacin (AK) is an antibacterial drug, but it has remarkable nephrotoxic and ototoxic side effects due to increase in reactive oxygen radicals. This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on AK-induced nephrotoxicity. Three different groups of rats (n = 6) were administered saline (control), AK (1.2 g/kg, intraperitoneally), ALA (100 mg/kg, p.o.) and AK combination (ALA one day before the AK for five days). Renal function, oxidative stress markers and histological changes were evaluated at the end of the experiment. Malondialdehyde was increased as an indicator of free radical formation in AK-induced group and decreased with ALA treatment. While catalase activity was increased significantly, superoxide dismutase and glutathione peroxidase activities were not statistically significant increased with ALA treatment. The result showed that AK enhanced levels of urea, creatinine and blood urea nitrogen in serum significantly. Administration of ALA reduced these levels of biochemical markers. Histopathological observations were confirmed by biochemical findings. In conclusion, ALA is suggested to be a potential candidate to ameliorate AK-induced nephrotoxicity.

  16. Alpha-lipoic acid protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy

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    Cao, Xueming; Chen, Aihua, E-mail: aihuachen2012@sina.com; Yang, Pingzhen; Song, Xudong; Liu, Yingfeng; Li, Zhiliang; Wang, Xianbao; Wang, Lizi; Li, Yunpeng

    2013-11-29

    Highlights: •We observed the cell viability and death subjected to H/R in H9c2 cardiomyocytes. •We observed the degree of autophagy subjected to H/R in H9c2 cardiomyocytes. •LA inhibited the degree of autophagy in parallel to the enhanced cell survival. •LA inhibited the autophagy in parallel to the decreased total cell death. •We concluded that LA protected cardiomyocytes against H/R by inhibiting autophagy. -- Abstract: Hypoxia/reoxygenation (H/R) is an important in vitro model for exploring the molecular mechanisms and functions of autophagy during myocardial ischemia/reperfusion (I/R). Alpha-lipoic acid (LA) plays an important role in the etiology of cardiovascular disease. Autophagy is widely implicated in myocardial I/R injury. We assessed the degree of autophagy by pretreatment with LA exposed to H/R in H9c2 cell based on the expression levels of Beclin-1, LC3II/LC3I, and green fluorescent protein-labeled LC3 fusion proteins. Autophagic vacuoles were confirmed in H9c2 cells exposed to H/R using transmission electron microscopy. Our findings indicated that pretreatment with LA inhibited the degree of autophagy in parallel to the enhanced cell survival and decreased total cell death in H9c2 cells exposed to H/R. We conclude that LA protects cardiomyocytes against H/R injury by inhibiting autophagy.

  17. Radioprotection by alpha-lipoic acid palladium complex formulation (POLY-MVA) in mice.

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    Ramachandran, Lakshmy; Krishnan, Chirakkal V; Nair, Cherupally Krishnan Krishnan

    2010-08-01

    The dietary supplement, POLY-MVA, containing palladium alpha-lipoic acid complex was examined for its efficacy as a radioprotector in mice exposed to whole-body gamma-radiation. Oral administration of POLY-MVA enhanced endogenous spleen colony formation in animals exposed to a sublethal dose of 6 Gy gamma-radiation. Alkaline comet assay revealed that the nuclear DNA comet parameters such as percent DNA in tail, tail length, tail moment, and olive tail moment, of the bone marrow cells and spleen cells, were found increased following whole-body gamma-irradiation. The radiation-induced DNA damage in these cells was reduced when POLY-MVA was administered to animals exposed to a lethal dose of 8 Gy whole-body gamma-radiation. The administration of POLY-MVA significantly reduced the gamma-radiation-induced mortality and also aided recovery from the radiation-induced loss of body weight in mice surviving after 8 Gy gamma-radiation exposure. These results suggest the potential use of POLY-MVA as a radioprotector in cases of planned radiation exposures.

  18. Protective effect of alpha-lipoic acid on cypermethrin-induced oxidative stress in Wistar rats.

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    Mignini, F; Nasuti, C; Fedeli, D; Mattioli, L; Cosenza, M; Artico, M; Gabbianelli, R

    2013-01-01

    Cypermethrin (CY), a class II pyrethroid pesticide, is globally used to control insects in the household and in agriculture. Despite beneficial roles, its uncontrolled and repetitive application leads to unintended effects in non-target organisms. In light of the relevant anti-oxidant properties of alpha-lipoic acid (ALA), in the work described herein we tested the effect of a commercially available ALA formulation on cypermethrin CY)-induced oxidative stress in Wistar rats. The rats were orally administered with 53.14 mg/kg of ALA and 35.71 mg/kg of CY for 60 days. The treatment with CY did not induce changes in either locomotor activities or in body weight. Differences were observed on superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation that were re-established by ALA treatment at similar levels of the placebo group. Furthermore, ALA formulation increased glutathione (GSH) level and glutathione peroxidase (GPx) activity. Because of the widespread use of CY, higher amounts of pesticide residues are present in food, and a diet supplementation with ALA could be an active free radical scavenger protecting against diseases associated with oxidative stress.

  19. Treatment with alpha-lipoic acid reduces asymmetric dimethylarginine in patients with type 2 diabetes mellitus.

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    Mittermayer, Friedrich; Pleiner, Johannes; Francesconi, Mario; Wolzt, Michael

    2010-01-01

    Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes mellitus (T2DM). It has been shown that alpha-lipoic acid (ALA) improves endothelial function and oxidative stress in these patients. The present study investigated if ALA reduces ADMA in patients with T2DM. Plasma concentrations of ADMA, L-arginine and symmetric dimethylarginine (SDMA) were determined in a double-blind, randomized, placebo-controlled study in patients with T2DM. Intravenous ALA (n = 16) or placebo (n = 14) was administered daily for 3 weeks. ALA reduced ADMA while no change was observed with placebo (mean change -0.05 micromol/1[95% CI: -0.01; -0.09] vs. 0.01 micromol/1 [95% CI: -0.05; -0.03]; ANOVA p = 0.031). SDMA and L-arginine were not affected by ALA. In conclusion ALA treatment reduces ADMA in patients with T2DM. Long-term studies need to demonstrate if ALA may cause cardiovascular risk reduction.

  20. Ability of alpha-lipoic acid to reverse the diabetic cystopathy in a rat model

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    Yuan-jun JIANG; Da-xin GONG; Hai-bo LIU; Chun-ming YANG; Zhi-xi SUN; Chui-ze KONG

    2008-01-01

    Aim: The present study was conducted to investigate whether alpha-lipoic acid (α-LA) is able to reverse impaired bladder function induced by diabetes in a rat model and to explore the possible mechanism mediating the effect. Methods: Male Sprague-Dawley rats were divided randomly into 3 age-matched groups: control, diabetes mellitus (DM) treated with vehicle, and DM with α-LA treatment. The diabetic rats were induced by a single intraperitoneal (ip) injection of streptozotocin (60 mg/kg). Six weeks after the induction of DM, the two groups received another 6 weeks of treatment with vehicle or α-LA (100 mg/kg, ip). Body weight and blood glucose levels were measured weekly. The bladder function was evaluated by in vitro cystometry. The oxidative stress status was determined by biochemical methods, and the level of nerve growth factor was investigated by enzyme-linked immunosorbent assay. Results: The streptozotocin-induced diabetic rats showed impaired bladder function characterized by increased bladder capacity, decreased bladder contractility (voiding efficiency), and an increase in residual urine. Treat-ment with α-LA significantly normalized the increased bladder capacity for induc-ing voiding, single-voided volume, and post-void residual volume, α-LA treat-ment significantly reversed the increased level of malondialdehyde and reduced the activities of both superoxide dismutase and catalase. DM caused a decrease in the bladder nerve growth factor (NGF) level, and α-LA upregulated the level of NGF in the diabetic rat bladder. Conclusion: These results indicate that α-LA has a beneficial effect on diabetes-induced cystopathy by ameliorating oxidative stress and normalizing the NGF level in the bladder.

  1. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

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    Lee Jung Eun

    2012-09-01

    Full Text Available Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF rats. Methods Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry. Results Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1 and connective tissue growth factor (CTGF were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA. Conclusions ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

  2. Attenuation of uremia by orally feeding alpha-lipoic acid on acetaminophen induced uremic rats.

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    Pradhan, Shrabani; Mandal, Shreya; Roy, Suchismita; Mandal, Arpita; Das, Koushik; Nandi, Dilip K

    2013-04-01

    Uremia means excess nitrogenous waste products in the blood & their toxic effects. An acute acetaminophen (paracetamol, N-acetyl p-aminophenol; APAP) overdose may result into potentially fatal hepatic and renal necrosis in humans and experimental animals. The aims of this present study were to investigate the protective effect of alpha-lipoic acid (ALA) on oxidative stress & uremia on male albino rats induced by acetaminophen. The study was performed by 24 albino male Wister strain rats which were randomly divided into four groups: Group I, control - receives normal food and water, Groups II, III & IV receive acetaminophen interperitoneally at the dose of 500 mg/kg/day for 10 days, from 11th day Groups III & IV were treated with ALA at the dose of 5 mg & 10 mg/100 g/day for 15 days, respectively. After 25 days of treatment, it was observed that there was a significant increase in plasma urea, creatinine, sodium and malondialdehyde (MDA) levels (p < 0.05) but a significant decrease in super oxide dismutase (SOD) & catalase activity & potassium level in uremic group is compared with control group & there was a significant increase in SOD & catalase (p < 0.05) & a significant decrease in serum urea, creatinine & Na and MDA (p < 0.05) in Group III & Group IV is compared with Group II & significant changes were observed in high ALA dose group. In conclusion it was observed that the ALA has nephroprotective activities by biochemical observations against acetaminophen induced uremic rats.

  3. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

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    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  4. Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

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    Liu, Ruixing; Wang, Yanling; Pu, Mingliang

    2016-01-01

    Purpose This study was conducted to determine whether alpha lipoic acid (ALA) promotes the survival of retinal ganglion cells (RGCs) in a rat model of optic nerve crush (ONC) injury and to investigate the neuroprotective mechanisms of ALA in the retina in this ONC injury model. Methods Adult male Sprague-Dawley rats (180–220 g) were subjected to ONC injury surgery. ALA (63 mg/kg) was injected intravenously 1 day before or after the ONC injury. Animals were euthanized after 10 days, and the number of ganglion cells positive for RNA-binding protein with multiple splicing (Rbpms), which is an RGC marker, were counted on the whole mount retinas. In addition, immunofluorescence and immunoblotting were performed to examine the localization and levels of erythropoietin receptor (EPOR) and neurotrophin-4/5 (NT4/5) in the retinas in all experimental groups. To determine whether the EPO/EPOR signaling pathway was involved in the ALA antioxidant pathway, the rats were subjected to ruxolitinib (INCB018424, 0.25 mg/kg, bid, intraperitoneal, i.p.) treatment after the animals were injected intravenously with ALA 1 day before ONC injury. Results The average number of Rbpms-positive cells/mm2 in the control group (sham-operated group), the ONC group, the ALA-ONC group, and the ONC-ALA group retinas was 2219±28, 418±8, 848±22, and 613±18/mm2, respectively. The ALA-ONC and ONC-ALA groups showed a statistically significantly increased RGC survival rate compared to the ONC group. There were statistical differences in the RGC survival rates between the ALA-ONC (39%) and ONC-ALA groups (28%; p<0.05). Immunofluorescent labeling showed that EPOR and NT4/5 expression was significant in the retinal ganglion cell layer (GCL). At the same time, western blot analysis revealed that ALA induced upregulation of EPOR protein and NT4/5 protein expression in the retina after ONC injury. However, INCB018424 reversed the protective effects of ALA on the ONC retinas. Conclusions ALA has

  5. Critical appraisal of the use of alpha lipoic acid (thioctic acid in the treatment of symptomatic diabetic polyneuropathy

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    McIlduff CE

    2011-09-01

    Full Text Available Courtney E McIlduff, Seward B RutkoveDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USABackground: The most common of the neuropathies associated with diabetes mellitus, diabetic sensorimotor polyneuropathy (DSPN is a syndrome of diffuse, length-dependent, symmetric nerve dysfunction. The condition is linked with substantial morbidity, frequent healthcare utilization, and compromised quality of life due to related discomfort. Correspondingly, antidepressants, anticonvulsants, and opioids are regularly prescribed with the goal of pain control. However, the agents rarely provide complete pain relief and fail to address progression of the disorder. Whereas strict blood glucose control can slow the onset and worsening of DSPN, near-normoglycemia is not easily attainable. Evidence implicating oxidative processes in the pathogenesis of DSPN offers one potentially important therapeutic avenue. Due to its properties as a potent antioxidant, alpha lipoic acid (ALA could mitigate the development of DSPN and attenuate resultant symptoms and signs. Approved for treatment of DSPN in Germany, the agent is not more widely used due to uncertainty about its efficacy and reported adverse effects. Here we review the effectiveness and tolerability of ALA in the treatment of symptomatic DSPN.Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched for English-language literature on the topic. Randomized, blinded studies comparing parenteral and oral ALA with placebo in the treatment of peripheral neuropathy in diabetic adults were selected. Analysis included studies with a level of evidence of at least 2b.Results: The current appraisal summarizes data from 1160 participants in the ALADIN, SYDNEY, ORPIL, SYDNEY 2, and ALADIN III trials. In four of the studies, ALA provided significant improvement in manifestations of DSPN.Conclusion: Treatment with ALA 600 mg iv daily for 3 weeks represents a well-tolerated and effective

  6. Alpha-Lipoic Acid and Antioxidant Diet Help to Improve Endothelial Dysfunction in Adolescents with Type 1 Diabetes: A Pilot Trial

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    Andrea Scaramuzza

    2015-01-01

    Full Text Available After evaluating the prevalence of early endothelial dysfunction, as measured by means of reactive hyperemia in adolescents with type 1 diabetes, we started a 6-month, double-blind, randomized trial to test the efficacy of an antioxidant diet (± alpha-lipoic acid supplementation to improve endothelial dysfunction. Seventy-one children and adolescents, ages 17 ± 3.9 yrs, with type 1 diabetes since 9.5 ± 5.3 yrs, using intensified insulin therapy, were randomized into 3 arms: (a antioxidant diet 10.000 ORAC + alpha-lipoic acid; (b antioxidant diet 10.000 ORAC + placebo; (c controls. BMI, blood pressure, fasting lipid profile, HbA1c, insulin requirement, dietary habits, and body composition were determined in each patient. An antioxidant diet significantly improved endothelial dysfunction when supplemented with alpha-lipoic acid, unlike diet with placebo or controls. A significant reduction in bolus insulin was also observed. We speculate that alpha-lipoic acid might have an antioxidant effect in pediatric diabetes patients by reducing insulin.

  7. alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy.

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    Alleva, Renata; Nasole, Emanuele; Di Donato, Ferruccio; Borghi, Battista; Neuzil, Jiri; Tomasetti, Marco

    2005-07-29

    Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, prolonged exposure to high concentrations of oxygen induces production of reactive oxygen species, causing damage to the cells. Thus, antioxidant supplementation has been proposed as an adjuvant to attenuate such deleterious secondary effects. We evaluated the effects of alpha-lipoic acid (LA) in patients affected by chronic wounds undergoing HBO treatment. LA supplementation efficiently reduces both the lipid and DNA oxidation induced by oxygen exposure. LA exerted its antioxidant activity by directly interacting with free radicals or by recycling vitamin E. An inhibitory effect of LA on the pro-inflammatory cytokine interleukin-6 was observed. Taken together, we demonstrated an adjuvant effect of LA in HBO therapy used for impaired wound healing treatment. We propose that LA may be used to further promote the beneficial effects of HBO therapy.

  8. Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats

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    Kim, Jin Hyun; Kim, Kyung Mi; Jung, Myeong Hee; Jung, Jung Hwa; Kang, Ki Mun; Jeong, Bae Kwon; Kim, Jin Pyeong; Park, Jung Je; Woo, Seung Hoon

    2016-01-01

    Purpose Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. Results ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-β1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. Materials and Methods Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. Conclusions Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer. PMID:27072584

  9. Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

    OpenAIRE

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-01-01

    Introduction: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. Aim of the study: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Material and methods: Forty adult male rats were divided into ...

  10. Palladium alpha-lipoic acid complex formulation enhances activities of Krebs cycle dehydrogenases and respiratory complexes I-IV in the heart of aged rats.

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    Sudheesh, N P; Ajith, T A; Janardhanan, K K; Krishnan, C V

    2009-08-01

    Age-related decline in the capacity to withstand stress, such as ischemia and reperfusion, results in congestive heart failure. Though the mechanisms underlying cardiac decay are not clear, age dependent somatic damages to mitochondrial DNA (mtDNA), loss of mitochondrial function, and a resultant increase in oxidative stress in heart muscle cells may be responsible for the increased risk for cardiovascular diseases. The effect of a safe nutritional supplement, POLY-MVA, containing the active ingredient palladium alpha-lipoic acid complex, was evaluated on the activities of the Krebs cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV in heart mitochondria of aged male albino rats of Wistar strain. Administration of 0.05 ml/kg of POLY-MVA (which is equivalent to 0.38 mg complexed alpha-lipoic acid/kg, p.o), once daily for 30 days, was significantly (pKrebs cycle dehydrogenases, and mitochondrial electron transport chain complexes. The unique electronic and redox properties of palladium alpha-lipoic acid complex appear to be a key to this physiological effectiveness. The results strongly suggest that this formulation might be effective to protect the aging associated risk of cardiovascular and neurodegenerative diseases.

  11. Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke.

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    Wu, Ming-Hsiu; Huang, Chao-Ching; Chio, Chung-Ching; Tsai, Kuen-Jer; Chang, Ching-Ping; Lin, Nan-Kai; Lin, Mao-Tsun

    2016-09-01

    Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both α-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-α) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha-lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively.

  12. Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms

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    Hermann R

    2014-11-01

    Full Text Available Robert Hermann,1 Julius Mungo,2 Peter Jürgen Cnota,2 Dan Ziegler3 1Clinical Research Appliance (cr appliance, Gelnhausen, Germany; 2MEDA Pharma GmbH & Co KG, Bad Homburg, Germany; 3Institute for Clinical Diabetology, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany Abstract: The present study aimed to examine the enantiomer-selective pharmacokinetics (PK, relative bioavailability (Frel, and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA. In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200; two 300 mg tablets (T 300; one 600 mg tablet (T 600; and a racemic ALA solution (OS. All tablet formulations (Thioctacid HR were considered test treatments, while the OS (Thioctacid, 600 T served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+- and S-(–-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax and total exposure (area under the curve [AUC]0–t were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax values ranging from 0.33–0.5 hours. The Frel of all tablet formulations was comparable, with R-(+-enantiomer Cmax test/reference ratios ranging from 36% (T 600 to 43% (T 200, and R-(+-enantiomer AUC test/reference ratios ranging from 64% (T 600 to 79% (T 300, indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC. An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA

  13. Role of alpha-lipoic acid in the management of anemia in patients with chronic renal failure undergoing hemodialysis

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    El-Nakib GA

    2013-08-01

    Full Text Available Gehad A El-Nakib,1 Tarek M Mostafa,2 Tarek M Abbas,4 Mamdouh M El-Shishtawy,3 Mokhtar M Mabrouk,2 Mohammed A Sobh41Mansoura University Hospitals, Mansoura, Egypt; 2Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 4Urology and Nephrology Centre, Faculty of Medicine, Mansoura University, Mansoura, EgyptIntroduction: Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and resources. This study investigates the role of alpha-lipoic acid (ALA in end stage renal disease patients undergoing hemodialysis. By the virtue of its antioxidative effects, ALA is expected to act as an erythropoietin (EPO adjuvant, and also has extended beneficial effects on endothelial dysfunction.Methods: Forty-four patients undergoing hemodialysis and receiving EPO were randomized into two groups: the first group received ALA 600 mg once daily for 3 months; while the other group represented the control group. Parameters measured at baseline and at end of study were hemoglobin, EPO doses, EPO resistance index (ERI, iron store indices, malondialdehyde, oxidized low-density lipoprotein (ox-LDL, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and asymmetric dimethylarginine (ADMA, as well as routine laboratory follow-up.Results: EPO doses and ERI were significantly decreased in the treatment group, while they did not change in the control group. Hemoglobin, iron store indices, malondialdehyde, oxidized ox-LDL, IL-6, TNF-α, and ADMA were similar in both treatment and control groups at baseline, and did not change by the end of study period. Likewise, routine laboratory measures were not affected by the treatment.Conclusion: ALA could be used in hemodialysis patients to reduce requirements for EPO. However, larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients

  14. α硫辛酸治疗糖尿病周围神经病变的研究进展%Alpha-lipoic Acid for Diabetic Peripheral Neuropathy

    Institute of Scientific and Technical Information of China (English)

    张孝丽

    2011-01-01

    The large number of mitochondrial superoxides produced in response to hyperglycemia is an important cause of diabetic peripheral neuropathy ( DPN).Alpha-lipoic acid is a powerful antioxidant that eliminates the products of oxidative stress and regenerates other antioxidants.Alpha-lipoic acid inhibits neural oxidative stress, increases nerval blood flow to speed up nerve conduction velocity, and promotes nerval Na+-K+ adenosine triphosphate activity and other mechanisms to improve the symptoms of DPN.Multiple clinical trials show that α-lipoic acid is effective and safe for the treatment of DPN.%高糖时机体产生大量线粒体超氧化物是糖尿病周围神经病变(DPN)的重要发病机制.α硫 辛酸是一种强有力的抗氧化剂,可以清除氧化应激产物,再生其他抗氧化剂.通过阻抑神经内氧化应激状态,增加神经营养血管的血流量,加快神经传导速度、增加神经Na+-K+三磷酸腺苷酶活性等机制改善 DPN症状.多项临床试验证实,α硫辛酸治疗 DPN安全、有效.

  15. The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.

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    Jin, Heung Yong; Lee, Kyung Ae; Wu, Jin Zu; Baek, Hong Sun; Park, Tae Sun

    2014-12-01

    In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

  16. Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory.

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    Mahboob, Aamra; Farhat, Syeda Mehpara; Iqbal, Ghazala; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf; Nabavi, Seyed Mohammad; Ahmed, Touqeer

    2016-04-01

    Aluminum (Al) is a neurotoxic agent which readily crosses the blood-brain-barrier (BBB) and accumulates in the brain leading to neurodegenerative disorders, characterised by cognitive impairment. Alpha-lipoic acid (ALA) is an antioxidant and has a potential to improve cognitive functions. This study aimed to evaluate the neuroprotective effect of ALA in AlCl3-induced neurotoxicity mouse model. Effect of ALA (25mg/kg/day) was evaluated in the AlCl3-induced neurotoxicity (AlCl3 150 mg/kg/day) mouse model on learning and memory using behaviour tests and on the expression of muscarinic receptor genes (using RT-PCR), in hippocampus and amygdala. Following ALA treatment, the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) were significantly improved (pnovelty preference (p<0.001) comparative to the AlCl3-treated group. Fear extinction memory was remarkably restored (p<0.001) in ALA-treated group demonstrated by reduced freezing response as compared to the AlCl3-treated group which showed higher freezing. In-silico analysis showed that racemic mixture of ALA has higher binding affinity for M1 and M2 compared to acetylcholine. These novel findings highlight the potential role of ALA in cognitive functions and cholinergic system enhancement thus presenting it an enviable therapeutic candidate for the treatment of neurodegenerative disorders.

  17. The protective effect of alpha lipoic acid on Schwann cells exposed to constant or intermittent high glucose.

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    Sun, Lian-Qing; Chen, Ying-Ying; Wang, Xuan; Li, Xiao-Jin; Xue, Bing; Qu, Ling; Zhang, Ting-Ting; Mu, Yi-Ming; Lu, Ju-Ming

    2012-10-01

    Diabetic peripheral neuropathy (DPN) is one of the most common and costly microvascular complications of diabetes, and no effective therapy exists. Previous studies have demonstrated that oxidative stress may be the unifying factor for the damaging effect of hyperglycemia. The aim of this study was to examine the impact of treatment with Alpha lipoic acid (ALA) on the intermittent high glucose (IHG) or high glucose (HG)-induced oxidative stress-induced mitochondrial pathway activation and Schwann cells (SCs) apoptosis in vitro. Our results suggested that IHG and HG induced SCs apoptosis in both caspase-dependent and caspase-independent pathways related to oxidative stress. More importantly, the cytotoxic effect of IHG was significantly more potent than that of HG. Treatment with ALA inhibited the IHG and HG-induced oxidative stress and apoptosis in SCs. Furthermore, treatment with ALA down-regulated the Bax expression and the release of cytochrome c and AIF translocation, but up-regulated the Bcl-2 expression in SCs. Treatment with ALA attenuated the activation of caspase-3 and caspase-9 and minimized the cleavage of PARP in SCs. These findings suggest that variability in glycemic control could be more deleterious than a constant HG and ALA antagonized the IHG-induced oxidative stress, activation of mitochondrial pathway and apoptosis in SCs.

  18. The effectiveness of evening primrose oil and alpha lipoic acid in recovery of nerve function in diabetic rats

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    Abeer Mohamed Rashad

    2011-09-01

    Full Text Available Objectives: Diabetic polyneuropathy is a serious complication of diabetes mellitus and the most frequent neuropathy worldwide. Evening primrose oil (EPO is rich in omega-6 essential fatty acid component and gamma-linolenic acid. Alpha lipoic acid (ALPA has a protective effect against lipid peroxidation and helps in scavenging free radicals. Data regarding the effect of treatment with EPO on diabetic parameters and neuropathic manifestations are conflicting. This study aimed to determine the therapeutic efficacy of EPO and ALPA in correcting diabetic parameters and functional and structural neuropathic manifestations in streptozotocin (STZ induced diabetic rats.Materials and methods: In this study, the effects of two week oral treatment with EPO (1.25 g/kg was compared to that of ALPA (100 mg/kg and insulin (2 IU/day, utilized singly or in combination.Results: Compared with untreated diabetic rats, EPO and ALPA resulted in reduction of serum levels of glucose (p<0.05, total cholesterol (p<0.01, triglycerides (p<0.01, low density lipoprotein cholesterol (p<0.01, thiobarbituric acid reactive substance (a marker of oxidative stress (p<0.05, and increased in levels of high density lipoprotein cholesterol (p<0.05 and total antioxidant capacity (p<0.05. Enhanced positive effect was observed with combination therapy.Conclusion: This work indicates that EPO and ALPA, particularly when used in combination, improve glycemic control, lipid abnormalities and antioxidant capacity, thus restore the impaired functional properties of peripheral nerves to a great extent. J Clin Exp Invest 2011; 2 (3: 245-253.

  19. Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by receptor activator of nuclear factor-kappaB ligand and tumor necrosis factor-alpha.

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    Kim, Hyon Jong; Chang, Eun-Ju; Kim, Hyun-Man; Lee, Seung Bok; Kim, Hyun-Duck; Su Kim, Ghi; Kim, Hong-Hee

    2006-05-01

    The relationship between oxidative stress and bone mineral density or osteoporosis has recently been reported. As bone loss occurring in osteoporosis and inflammatory diseases is primarily due to increases in osteoclast number, reactive oxygen species (ROS) may be relevant to osteoclast differentiation, which requires receptor activator of nuclear factor-kappaB ligand (RANKL). Tumor necrosis factor-alpha (TNF-alpha) frequently present in inflammatory conditions has a profound synergy with RANKL in osteoclastogenesis. In this study, we investigated the effects of alpha-lipoic acid (alpha-LA), a strong antioxidant clinically used for some time, on osteoclast differentiation and bone resorption. At concentrations showing no growth inhibition, alpha-LA potently suppressed osteoclastogenesis from bone marrow-derived precursor cells driven either by a high-dose RANKL alone or by a low-dose RANKL plus TNF-alpha (RANKL/TNF-alpha). alpha-LA abolished ROS elevation by RANKL or RANKL/TNF-alpha and inhibited NF-kappaB activation in osteoclast precursor cells. Specifically, alpha-LA reduced DNA binding of NF-kappaB but did not inhibit IKK activation. Furthermore, alpha-LA greatly suppressed in vivo bone loss induced by RANKL or TNF-alpha in a calvarial remodeling model. Therefore, our data provide evidence that ROS plays an important role in osteoclast differentiation through NF-kappaB regulation and the antioxidant alpha-lipoic acid has a therapeutic potential for bone erosive diseases.

  20. Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

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    Chidiebere Uchendu

    2014-01-01

    Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

  1. Clinical Usefulness of Oral Supplementation with Alpha-Lipoic Acid, Curcumin Phytosome, and B-Group Vitamins in Patients with Carpal Tunnel Syndrome Undergoing Surgical Treatment

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    Giorgio Pajardi

    2014-01-01

    Full Text Available We investigated the clinical usefulness of oral supplementation with a combination product containing alpha-lipoic acid, curcumin phytosome, and B-group vitamins in 180 patients with carpal tunnel syndrome (CTS, scheduled to undergo surgical decompression of the median nerve. Patients in Group A (n=60 served as controls and did not receive any treatment either before or after surgery. Patients in Group B (n=60 received oral supplementation twice a day for 3 months both before and after surgery (totaling 6 months of supplementation. Patients in Group C (n=60 received oral supplementation twice a day for 3 months before surgery only. Patients in Group B showed significantly lower nocturnal symptoms scores compared with Group A subjects at both 40 days and 3 months after surgery (both P values <0.05. Moreover, patients in Group B had a significantly lower number of positive Phalen’s tests at 3 months compared with the other study groups (P<0.05. We conclude that oral supplementation with alpha-lipoic acid, curcumin phytosome, and B-group vitamins twice a day both before and after surgery is safe and effective in CTS patients scheduled to undergo surgical decompression of the median nerve.

  2. Rheology as a Tool to Predict the Release of Alpha-Lipoic Acid from Emulsions Used for the Prevention of Skin Aging.

    Science.gov (United States)

    Isaac, Vera Lucia Borges; Chiari-Andréo, Bruna Galdorfini; Marto, Joana Marques; Moraes, Jemima Daniela Dias; Leone, Beatriz Alves; Corrêa, Marcos Antonio; Ribeiro, Helena Margarida

    2015-01-01

    The availability of an active substance through the skin depends basically on two consecutive steps: the release of this substance from the vehicle and its subsequent permeation through the skin. Hence, studies on the specific properties of vehicles, such as their rheological behavior, are of great interest in the field of dermatological products. Recent studies have shown the influence of the rheological features of a vehicle on the release of drugs and active compounds from the formulation. In this context, the aim of this study was to evaluate the influence of the rheological features of two different emulsion formulations on the release of alpha-lipoic acid. Alpha-lipoic acid (ALA) was chosen for this study because of its antioxidant characteristics, which could be useful for the prevention of skin diseases and aging. The rheological and mechanical behavior and the in vitro release profile were assayed. The results showed that rheological features, such as viscosity, thixotropy, and compliance, strongly influenced the release of ALA from the emulsion and that the presence of a hydrophilic polymer in one of the emulsions was an important factor affecting the rheology and, therefore, the release of ALA.

  3. The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle.

    Science.gov (United States)

    Sherif, Saly; Bendas, Ehab R; Badawy, Sabry

    2014-02-01

    Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy

  4. Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms.

    Science.gov (United States)

    Hermann, Robert; Mungo, Julius; Cnota, Peter Jürgen; Ziegler, Dan

    2014-01-01

    The present study aimed to examine the enantiomer-selective pharmacokinetics (PK), relative bioavailability (Frel), and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA). In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females) received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200); two 300 mg tablets (T 300); one 600 mg tablet (T 600); and a racemic ALA solution (OS). All tablet formulations (Thioctacid HR) were considered test treatments, while the OS (Thioctacid, 600 T) served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+)- and S-(-)-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax) and total exposure (area under the curve [AUC]0-t) were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax) values ranging from 0.33-0.5 hours. The Frel of all tablet formulations was comparable, with R-(+)-enantiomer Cmax test/reference ratios ranging from 36% (T 600) to 43% (T 200), and R-(+)-enantiomer AUC test/reference ratios ranging from 64% (T 600) to 79% (T 300), indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC). An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA enantiomers indicated the absence of a significant sex effect for Cmax, as well as 20%-26% and 25%-32% higher R-(+)- and S-(-)-ALA enantiomer AUC outcomes in females when compared to males. The observed modest sex effect was comparable for both ALA enantiomers and across all formulations, and it did not appear

  5. Reduced Expression of Lipoic Acid Synthase Accelerates Diabetic Nephropathy

    OpenAIRE

    Yi, Xianwen; Xu, Longquan; Hiller, Sylvia; Kim, Hyung-Suk; Nickeleit, Volker; James, Leighton R; Maeda, Nobuyo

    2011-01-01

    Oxidative stress contributes to the pathogenesis of diabetic nephropathy. In mitochondria, lipoic acid synthase produces α-lipoic acid, an antioxidant and an essential cofactor in α-ketoacid dehydrogenase complexes, which participate in glucose oxidation and ATP generation. Administration of lipoic acid abrogates diabetic nephropathy in animal models, but whether lower production of endogenous lipoic acid promotes diabetic nephropathy is unknown. Here, we crossed mice heterozygous for lipoic ...

  6. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson's Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

    Science.gov (United States)

    de Araújo, Dayane Pessoa; De Sousa, Caren Nádia Soares; Araújo, Paulo Victor Pontes; Menezes, Carlos Eduardo de Souza; Sousa Rodrigues, Francisca Taciana; Escudeiro, Sarah Souza; Lima, Nicole Brito Cortez; Patrocínio, Manoel Claúdio Azevedo; Aguiar, Lissiana Magna Vasconcelos; Viana, Glauce Socorro de Barros; Vasconcelos, Silvânia Maria Mendes

    2013-01-01

    This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg) alone or associated with L-DOPA using an animal model of Parkinson's disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA) at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment. PMID:24023579

  7. Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study.

    Science.gov (United States)

    Rago, R; Marcucci, I; Leto, G; Caponecchia, L; Salacone, P; Bonanni, P; Fiori, C; Sorrenti, G; Sebastianelli, A

    2015-01-01

    The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS.

  8. Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    Ozbag Davut

    2009-01-01

    Full Text Available Abstract Objective Crush injury to the sciatic nerve causes oxidative stress. Alfa Lipoic acid (a-LA is a neuroprotective metabolic antioxidant. This study was designed to investigate the antioxidant effects of pretreatment with a-LA on the crush injury of rat sciatic nerve. Methods Forty rats were randomized into four groups. Group I and Group II received saline (2 ml, intraperitoneally and a-LA (100 mg/kg, 2 ml, intraperitoneally in the groups III and IV at the 24 and 1 hour prior to the crush injury. In groups II, III and IV, the left sciatic nerve was exposed and compressed for 60 seconds with a jeweler's forceps. In Group I (n = 10, the sciatic nerve was explored but not crushed. In all groups of rats, superoxide dismutase (SOD and catalase (CAT activities, as well as malondialdehyde (MDA levels were measured in samples of sciatic nerve tissue. Results Compared to Group I, Group II had significantly decreased tissue SOD and CAT activities and elevated MDA levels indicating crush injury (p < 0.05. In the a-LA treatment groups (groups III and IV, tissue CAT and SOD activities were significantly increased and MDA levels significantly decreased at the first hour (p < 0.05 and on the 3rd day (p < 0.05. There was no significant difference between a-LA treatment groups (p > 0.05. Conclusion A-LA administered before crush injury of the sciatic nerve showed significant protective effects against crush injury by decreasing the oxidative stress. A-LA should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects.

  9. Growth performance, intestinal morphology, and meat quality in relation to alpha-lipoic acid associated with vitamin C and E in broiler chickens under tropical conditions

    Directory of Open Access Journals (Sweden)

    Jaehong Yoo

    2016-03-01

    Full Text Available ABSTRACT This study was conducted to examine the effect of alpha-lipoic acid with vitamin C and E on growth performance, intestinal morphology, and meat quality in broiler chickens under tropical conditions. A total of 288 one-day-old male ROSS 308 chicks (40±0.1 g were used in a completely randomized design and allotted to one of six dietary treatments to form sixe replicates per treatment (eight birds per cage. The six dietary treatments were: a corn-soybean meal-based diet (NC; no antimicrobial compounds added with 8 ppm alpha-lipoic acid (ALA; 150 ppm vitamin C and 75 ppm vitamin E (E-75; E-75 plus ALA (E-75-ALA; 150 ppm vitamin C and 50 ppm vitamin E (E-50 plus ALA (E-50-ALA; and 150 ppm vitamin C and 25 ppm vitamin E (E-25 plus ALA (E-25-ALA. All dietary treatments were continuously provided in liquid form, dissolved in water. Birds were housed in a battery cage (n = 36, and were offered dietary treatments on an ad libitum basis. The ambient temperature was maintained at 32±1 ºC for the first three weeks and reduced gradually to 28 ºC by the end of the experiment (day 35 to induce moderate tropical condition. One bird per pen (n = 6, and another bird per pen (n = 6 were euthanized via cervical dislocation to obtain terminal ileum to measure villus height and crypt depth at day 21, and to harvest breast meat and drumsticks to evaluate meat quality traits at day 35, respectively. Dietary treatment E-75-ALA improved body weight and average daily gain compared with birds fed other dietary treatments from day 1 to day 35. Birds fed dietary treatment E-75-ALA and E-50-ALA had higher villus height than those fed the other dietary treatments at day 21. Dietary treatments E-75-ALA and E-50-ALA reduced thiobarbituric acid reactive substance (TBARS in drumsticks compared with other dietary treatments, but only treatment E-75-ALA decreased TBARS in breast meat at day 35. Liquid form of antioxidant compounds such as E-75-ALA can improve growth

  10. Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    LI Chun-jun; ZHANG Qiu-mei; LI Ming-zhen; ZHANG Jing-yun; YU Pei; YU De-min

    2009-01-01

    Background Cardiac failure is a leading cause of the mortality of diabetic patients.In part this is due to a specific cardiomyopathy,referred to as diabetic cardiomyopathy.Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease.This study aimed to test whether the antioxidant α-lipoic acid(α-LA)could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy.Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin(STZ)45 mg/kg.Experimental animals were randomly assigned to 3 groups:normal control(NC),diabetes(DM)and DM treated with α-LA (α-LA).The latter group was administered with α-LA(100 mg/kg ip per day),the remainder received the same volume vehicle.At weeks 4,8,and 12 after the onset of diabetes,cardiac apoptosis was examined by TUNEL assay.Cardiomyopathy was evaluated by assessment of cardiac structure and function.Oxidative damage was evaluated by the content of malondialdehyde(MDA),reduced glutathione(GSH)and the activity of manganese superoxide diamutase (Mn-SOD)in the myocardial mitochondria.Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blottingResults At 4,8,and 12 weeks after the onset of diabetes,significant reductions in TUNEL-positive cells,caspase-9,-3 expression,and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group.In the DM group,the content of MDA in the myocardial mitochondria was significantly increased,and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD.They were significantly improved by α-LA treatment.HE staining displayed structural abnormalities in diabetic hearts,while α-LA reversed this structural derangement.The index of cardiac function(±dp/dtmax)in the diabetes

  11. Gas-saturated solution process to obtain microcomposite particles of alpha lipoic acid/hydrogenated colza oil in supercritical carbon dioxide.

    Science.gov (United States)

    Mishima, Kenji; Honjo, Masatoshi; Sharmin, Tanjina; Ito, Shota; Kawakami, Ryo; Kato, Takafumi; Misumi, Makoto; Suetsugu, Tadashi; Orii, Hideaki; Kawano, Hiroyuki; Irie, Keiichi; Sano, Kazunori; Mishima, Kenichi; Harada, Takunori; Ouchi, Mikio

    2016-09-01

    Alpha lipoic acid (ALA), an active substance in anti-aging products and dietary supplements, need to be masked with an edible polymer to obscure its unpleasant taste. However, the high viscosity of the ALA molecules prevents them from forming microcomposites with masking materials even in supercritical carbon dioxide (scCO2). Therefore, the purpose of this study was to investigate and develop a novel production method for microcomposite particles for ALA in hydrogenated colza oil (HCO). Microcomposite particles of ALA/HCO were prepared by using a novel gas-saturated solution (PGSS) process in which the solid-dispersion method is used along with stepwise temperature control (PGSS-STC). Its high viscosity prevents the formation of microcomposites in the conventional PGSS process even under strong agitation. Here, we disperse the solid particles of ALA and HCO in scCO2 at low temperatures and change the temperature stepwise in order to mix the melted ALA and HCO in scCO2. As a result, a homogeneous dispersion of the droplets of ALA in melted HCO saturated with CO2 is obtained at high temperatures. After the rapid expansion of the saturated solution through a nozzle, microcomposite particles of ALA/HCO several micrometers in diameter are obtained.

  12. Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies.

    Science.gov (United States)

    Abdel-Daim, Mohamed M; Taha, Ramadan; Ghazy, Emad W; El-Sayed, Yasser S

    2016-01-01

    Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities.

  13. Ambazone-lipoic acid salt: Structural and thermal characterization

    Energy Technology Data Exchange (ETDEWEB)

    Kacso, Irina [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath street, 400293 Cluj-Napoca (Romania); Racz, Csaba-Pal; Santa, Szabolcs [Babes-Bolyai' University, Faculty of Chemistry, 11 Arany Janos street, Cluj-Napoca (Romania); Rus, Lucia [' Iuliu Hatieganu' University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Louis Pasteur street, 400349 Cluj-Napoca (Romania); Dadarlat, Dorin; Borodi, Gheorghe [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath street, 400293 Cluj-Napoca (Romania); Bratu, Ioan, E-mail: ibratu@gmail.com [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath street, 400293 Cluj-Napoca (Romania)

    2012-12-20

    Highlights: Black-Right-Pointing-Pointer Salt of Ambazone with lipoic acid obtained by solvent-drop grinding. Black-Right-Pointing-Pointer Ambazone lipoate salt crystallizes in monoclinic system. Black-Right-Pointing-Pointer FTIR data suggest the deprotonation of the lipoic acid. Black-Right-Pointing-Pointer Thermal behaviour different of ambazone salt as compared to the starting compounds. - Abstract: A suitable method for increasing the solubility, dissolution rate and consequently the bioavailability of poor soluble acidic or basic drugs is their salt formation. The aim of this study is to investigate the structural and thermal properties of the compound obtained by solvent drop grinding (SDG) method at room temperature, starting from the 1:1 molar ratios of ambazone (AMB) and {alpha}-lipoic acid (LA). The structural characterization was performed with X-ray powder diffraction (XRPD) and infrared spectroscopy (FTIR). The thermal behaviour of the obtained compound (AMB{center_dot}LA) was investigated by differential scanning calorimetry (DSC) and thermogravimetry (TG). The photopyroelectric calorimetry, in front detection configuration (FPPE), was applied to measure and compare the room temperature values of one dynamic thermal parameter (thermal effusivity) for starting and resulting compounds. Both structural and supporting calorimetric techniques pointed out a salt structure for AMB{center_dot}LA compound as compared to those of the starting materials.

  14. R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase.

    Science.gov (United States)

    Korotchkina, Lioubov G; Sidhu, Sukhdeep; Patel, Mulchand S

    2004-10-01

    The four pyruvate dehydrogenase kinase (PDK) and two pyruvate dehydrogenase phosphatase (PDP) isoenzymes that are present in mammalian tissues regulate activity of the pyruvate dehydrogenase complex (PDC) by phosphorylation/dephosphorylation of its pyruvate dehydrogenase (E1) component. The effect of lipoic acids on the activity of PDKs and PDPs was investigated in purified proteins system. R-lipoic acid, S-lipoic acid and R-dihydrolipoic acid did not significantly affect activities of PDPs and at the same time inhibited PDKs to different extents (PDK1>PDK4 approximately PDK2>PDK3 for R-LA). Since lipoic acids inhibited PDKs activity both when reconstituted in PDC and in the presence of E1 alone, dissociation of PDK from the lipoyl domains of dihydrolipoamide acetyltransferase in the presence of lipoic acids is not a likely explanation for inhibition. The activity of PDK1 towards phosphorylation sites 1, 2 and 3 of E1 was decreased to the same extent in the presence of R-lipoic acid, thus excluding protection of the E1 active site by lipoic acid from phosphorylation. R-lipoic acid inhibited autophosphorylation of PDK2 indicating that it exerted its effect on PDKs directly. Inhibition of PDK1 by R-lipoic acid was not altered by ADP but was decreased in the presence of pyruvate which itself inhibits PDKs. An inhibitory effect of lipoic acid on PDKs would result in less phosphorylation of E1 and hence increased PDC activity. This finding provides a possible mechanism for a glucose (and lactate) lowering effect of R-lipoic acid in diabetic subjects.

  15. The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats.

    Science.gov (United States)

    Yamamoto, H; Watanabe, T; Mizuno, H; Endo, K; Fukushige, J; Hosokawa, T; Kazusaka, A; Fujita, S

    2001-01-01

    The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

  16. Alpha lipoic acid protects lens from H2O2-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes

    Institute of Scientific and Technical Information of China (English)

    Yun Li; Ya-Zhen Liu; Jing-Ming Shi; Song-Bai Jia

    2013-01-01

    Objective: To determine whether alpha lipoic acid (LA) can effectively protect lenses from hydrogen peroxide (H2O2)-induced cataract. Methods: Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2, 0.2 mM of H2O2 plus 0.5 mM, 1.0 mM, or 2.0 mM of LA for 24 h. Cataract was assessed using cross line grey scale measurement. Superoxide dismutase (SOD), glutathione (GSH-Px), lactate dehydrogenase (LDH), and malondialdehyde (MDA) activity or level in lens homogenates was measured. Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay. Results: A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens’ epithelial cells, but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis. Furthermore, 0.2 mM of H2O2 significantly decreased SOD, GSH-Px, and LDH activity and significant increased MDA level in the lens, but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2. One mM of LA was found to be the most effective. Conclusions: LA can protect lens from H2O2-induced cataract. LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.

  17. Abrogation of cisplatin-induced nephrotoxicity in mice by alpha lipoic acid through ameliorating oxidative stress and enhancing gene expression of antioxidant enzymes.

    Science.gov (United States)

    El-Beshbishy, Hesham A; Bahashwan, Saleh A; Aly, Hamdy A A; Fakher, Hesham A

    2011-10-01

    Cisplatin is chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of present study is to investigate biochemical and molecular effects of alpha lipoic acid (ALA) to protect against cisplatin-induced nephrotoxicity in mice. Cisplatin (12 mg/kg/day) was administered i.p. for 4 days. Group of mice were given ALA (20 mg/kg/day) for 18 days. Another set were administered ALA for 4 days before and 14 days after cisplatin intoxication. The results obtained revealed that kidney/body weight ratio of cisplatin-treated mice was increased by +40%. ALA intake declined the ratio by -19%. Serum creatinine and urea levels were increased in cisplatin-treated mice by +375% and +69%, respectively. These changes were moved to normalcy upon ALA intake. Cisplatin treatment elevated malondialdehyde (MDA) by 27 fold and declined reduced glutathione (GSH) by -49%. Cisplatin decreased catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes by -47%, -49% and -59%, respectively. ALA decreased the MDA by -286% and increased the GSH, catalase, SOD and GPx levels by +60%, +81%, +90% and +38%, respectively. ALA increased mRNA expression of catalase, CuZn SOD and GPx genes near to normalcy compared to cisplatin-treated mice. Cisplatin-treated mice increased caspase-3-activity by +223%, nitric oxide (NO) by +74% and inducible nitric oxide synthase (iNOS) by 10 fold. ALA intake declined these changes by -43%, -45% and -73%, respectively. ALA may play renoprotective role on cisplatin-induced nephrotoxicity through antioxidant and antiapoptotic mechanisms combined with initiation of mRNA expression of antioxidant genes.

  18. Meta analysis of alpha lipoic acid combined with mecobalamin in the treatment of diabetic peripheral neuropathy%α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的Meta分析

    Institute of Scientific and Technical Information of China (English)

    刘慧竹

    2015-01-01

    Objective:To study the clinical curative effect of alpha lipoic acid combined with mecobalamin in diabetic peripheral neuropathy,and to do Meta analysis.Methods:512 patients with diabetic peripheral neuropathy were selected.They were randomly divided into the observation group and the control group.The observation group was given alpha lipoic acid combined with mecobalamin treatment.The control group was given mecobalamin monotherapy.The treatment effects of two groups were compared.Results:The clinical symptoms of the observation group were significantly reduced,the treatment total effective rate was higher,the curative effect was significantly better than that of the control group(P<0.05).Conclusion:Alpha lipoic acid combined with mecobalamin in the treatment of diabetic peripheral neuropathy has a significant clinical effect.%目的:研究α-硫辛酸联合甲钴胺对糖尿病周围神经病变的临床疗效,并对其做Meta分析。方法:收治糖尿病周围神经病变患者512例,随机分为观察组和对照组。观察组给予α-硫辛酸联合甲钴胺治疗,对照组给予甲钴胺单药治疗,分析两组治疗效果。结果:观察组临床症状明显减轻,治疗总有效率较高,疗效明显优于对照组(P<0.05)。结论:α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变具有显著的临床效果。

  19. The Effect of Coenzyme Q10 and Lipoic Acid Added to the Feed of Hens on Physical Characteristics of Eggs

    Directory of Open Access Journals (Sweden)

    Dušan Terčič

    2011-10-01

    Full Text Available This study was designed to investigate whether inclusions of coenzyme Q10, alpha lipoic acid and their combination into diets of hens improve egg quality characteristics. Forty-eight, 33 weeks old Lohmann Brown hens were assigned randomly to four groups of 12 hens each and fed either a basal diet or basal diet supplemented with 2 g/kg coenzyme Q10, 0.4 g/kg alpha lipoic acid and 2 g/kg coenzyme Q10 plus 0.4 g/kg alpha lipoic acid. The diets were fed for 12 weeks. Eggs were weekly examined for interior or exterior quality characteristics. There were no effects of dietary treatments on egg shape index. Coenzyme Q10 supplementation resulted in a reduction in egg shell colour (darker shells and yolk colour (paler yolks and higher incidence of blood and meat spots, which reduce the internal quality of the egg. Alpha lipoic acid had no effect on egg weight, egg shell colour, egg shell density, egg shell weight, egg shell thickness, yolk colour, incidence of blood and meat spots but increased shell strength, albumen height and Haugh units values were noted. Egg shell strength for hens supplemented with alpha lipoic acid was greater than for control hens. The results of the experiment indicated that alpha lipoic acid supplementation to the diet of layers may be of practical value due to the increased egg shell strength and better albumen characteristics without any adverse effect on other egg quality traits.

  20. Meta analysia of Alpha-Lipoic Acid and Mecobalamin in the treatment of diabetic peripheral neuropathy%α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的Meta分析

    Institute of Scientific and Technical Information of China (English)

    李竞; 张琳; 赵湜

    2013-01-01

    Objective To evaluate and analyze the clinical effect of Alpha-Lipoic Acid combined with Mecobalamin in the treatment of diabetic peripheral neuropathy (DPN) by Meta-analysis. Methods The domestic published studies which contained Alpha-Lipoic Acid combined with Mecobalamin in the treatment of diabetic peripheral neuropathy were retrieved in Chinese CNKI and Wanfang databases from 2008 to 2012. The data was extracted for summarizing all studies, testing the overall effect and analyzing the publication bias by Rev Man 5.0. Results A total of 859 DPN patients from 12 literatures were obtained in the analysis. The homogeneity were discovered between the studies (P = 0.85 > 0.05), Meta analysis showed that the therapeutic effect of Lipoic Acid combined with Mecobalamin in treated group was superior to control group [P < 0.000 01, (OR = 5.30, 95%CI: 3.59-7.82)]. Conclusion Comparing with Mecobalamin, Lipoic Acid combined with Mecobalamin is a better therapy for DPN.%目的 用Meta分析对临床使用α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的方案进行分析,评价其治疗效果.方法 利用中国学术期刊全文数据库(CNKI)、万方全文数据库,检索到2008~2012年国内发表的α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变临床试验的相关文献,应用Meta分析软件包Rev Man 5.0对各研究结果进行数据合并,并进行发表偏倚分析.结果 共纳入文献12篇,859例糖尿病周围神经病变患者,各研究结果间存在同质性(P = 0.85 > 0.05),α-硫辛酸与甲钴胺治疗联合治疗组总体有效率明显高于对照组[P < 0.000 01,(OR = 5.30,95%CI:3.59~7.82)].结论 与单独使用甲钴胺相比,采用α-硫辛酸联合甲钴胺的方法治疗糖尿病周围神经病变更加有效.

  1. α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的疗效%Curative effect of alpha lipoic acid combined with mecobalamin in the treatment of diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    王静; 李国华

    2015-01-01

    Objective:To explore the curative effect of alpha lipoic acid combined with mecobalamin in the treatment of diabetic peripheral neuropathy.Methods:86 patients with diabetes were selected.They were randomly divided into the treatment group and the control group.The control group was treated with mecobalamin,and the treatment group was treated with lipoic acid combined with mecobalamin.We compared the efficacy.Results:The treatment effect of treatment group was better than the control group, and the nerve conduction velocity was increased significantly than before treatment(P<0.05).Conclusion:Lipoic acid combined with mecobalamin can significantly improve the situation of diabetic peripheral neuropathy.%目的:探讨α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变患者的临床疗效。方法:收治糖尿病患者86例,随机分为治疗组和对照组,对照组使用甲钴胺治疗,治疗组采用硫辛酸联合甲钴胺治疗,比较疗效。结果:治疗组的治疗效果要优于对照组,神经传导速度较治疗前有显著提高(P<0.05)。结论:硫辛酸联合甲钴胺能显著地改善糖尿病周围神经病变情况。

  2. α-硫辛酸治疗糖尿病神经病变对患者总症状评分的影响%Effect of alpha-lipoic acid on TSS in patients with diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    冯英; 张佼佼; 刘春燕

    2013-01-01

    Objective: To evaluate the effect of alpha-lipoic acid on diabetic peripheral neuropathy. Methods: A lot of 64 diabetic peripheral neuropathy patients col ected from 2011 to 2012 in our hospital were assigned to alpha-lipoic acid (n=32, experiment group) or glutathione(n=32, control group), for 14 days. The primary outcome measure was the change from baseline of the TSS, including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Results: After use of alpha-lipoic acid, the TSS decreased significantly by 4.37 points, as compared with that at the baseline(P<0.01). TSS was more significantly decreased in the experiment group than in the control group (P<0.05). No adverse reactions occurred in both groups. Conclusions: As compared with glutathione, ALA could improved neuropathic symptoms effectively with no adverse reactions.%  目的:评价α-硫辛酸治疗2型糖尿病周围神经病变的有效性。方法:将2011年至2012年我院收治2型糖尿病周围神经病变患者共64例随机分为试验组(n=32)和对照组(n=32),其中试验组使用α-硫辛酸治疗,对照组使用谷胱甘肽治疗,治疗前后对其进行TSS。结果:试验组患者应用α-硫辛酸治疗后,TSS较治疗前改善4.37分(P <0.01),且未见明显不良反应。结论:α-硫辛酸相对于谷胱甘肽可明显改善2型糖尿病患者周围神经病变的症状,且无明显不良反应。

  3. Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice.

    Science.gov (United States)

    Guo, Jun; Gao, Shixing; Liu, Zhiqing; Zhao, Ruqian; Yang, Xiaojing

    2016-10-01

    Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha-lipoic acid (α-LA) has been demonstrated to function as an anti-inflammatory and anti-oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α-LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non-esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation-, lipid- and energy metabolism-related genes and proteins was determined by quantitative real-time polymerase chain reaction and western blotting. The results indicated that α-LA significantly decreased the epididymis fat weight index and the non-esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α-LA reduced their expression. The LPS-induced expression of nuclear factor-κB protein was decreased by α-LA. Regarding lipid metabolism, α-LA significantly counteracted the inhibitory effects of LPS on the expression of hormone-sensitive lipase gene and protein. α-LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α-LA significantly increased the expression of most of mitochondrial DNA-encoded genes compared with the control and LPS group. Accordingly, α-LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.

  4. Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

    2016-08-01

    The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

  5. Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury.

    Science.gov (United States)

    Rocamonde, B; Paradells, S; Barcia, J M; Barcia, C; García Verdugo, J M; Miranda, M; Romero Gómez, F J; Soria, J M

    2012-11-01

    After trauma brain injury, a large number of cells die, releasing neurotoxic chemicals into the extracellular medium, decreasing cellular glutathione levels and increasing reactive oxygen species that affect cell survival and provoke an enlargement of the initial lesion. Alpha-lipoic acid is a potent antioxidant commonly used as a treatment of many degenerative diseases such as multiple sclerosis or diabetic neuropathy. Herein, the antioxidant effects of lipoic acid treatment after brain cryo-injury in rat have been studied, as well as cell survival, proliferation in the injured area, gliogenesis and angiogenesis. Thus, it is shown that newborn cells, mostly corresponded with blood vessels and glial cells, colonized the damaged area 15 days after the lesion. However, lipoic acid was able to stimulate the synthesis of glutathione, decrease cell death, promote angiogenesis and decrease the glial scar formation. All those facts allow the formation of new neural tissue. In view of the results herein, lipoic acid might be a plausible pharmacological treatment after brain injury, acting as a neuroprotective agent of the neural tissue, promoting angiogenesis and reducing the glial scar formation. These findings open new possibilities for restorative strategies after brain injury, stroke or related disorders.

  6. 加巴喷丁联合α-硫辛酸治疗糖尿病痛性神经病变的疗效观察%Effect of Alpha Lipoic Acid and Gabapentin for Diabetic Painful Neuropathy

    Institute of Scientific and Technical Information of China (English)

    李群; 于凤泉

    2015-01-01

    Objective To observe the effect of alpha lipoic acid and gabapentin for diabetic painful neuropathy and its effects on inlfammatory factors. Method 98 diabetic neuropathy patients were at random divided into 3 groups: routine group, alpha lipoic acid group and combination group. They were all given conventional treatment. Alpha lipoic acid group were treated with alpha lipoic acid, and combination group were given the gabapentin combination with alpha lipoic acid. We observed the changes of nerve conduction velocity, hs-CRP, TNF-α, IL-6 and the effect evaluation of DNP before and after treatment. Results The total efifcacy rate in the combination group was signiifcant better than that in routine group and alpha lipoic acid group(P<0.01); There is a signiifcant Improvement of nerve conduction velocity and a decrease of inlfammatory factors in three groups after three weeks treatment(P<0.05). Conclusion Gabapentin combined with alpha lipoic acid could be an effective therapy for diabetic painful neuropathy.%目的:观察加巴喷丁联合α-硫辛酸对糖尿病痛性神经病变的疗效及其对炎性因子的影响。方法98例糖尿病痛性神经病变患者随机分为3组:常规组、α-硫辛酸组和综合组,3组患者均给予常规治疗,α-硫辛酸组加用α-硫辛酸治疗,综合组采用加巴喷丁联合α-硫辛酸治疗。分别于治疗前和治疗3周后检测神经传导速度、血清超敏C反应蛋白(hypersensitivec-reactiveprotein,hs-CRP)、肿瘤坏死因子(tumornecrosisfactor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6),同时观察记录治疗前后疼痛强度变化,进行疗效评价。结果治疗3周后,综合组总有效率明显高于α-硫辛酸组和常规组(P<0.01)。3组患者神经传导速度均有升高、血清炎性因子均

  7. α硫辛酸用于早期糖尿病肾病的临床效果观察%Clinical effect of alpha lipoic acid on early diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    姜文娟; 周连华; 张进安

    2013-01-01

    目的 观察α硫辛酸应用于早期糖尿病肾病(DN)的临床疗效.方法 70例早期DN患者随机分为使用α硫辛酸组35例(观察组)和未使用α硫辛酸治疗组35例(对照组).对照组予以常规的控制血糖等治疗;治疗组加用d硫辛酸300 mg/d静脉滴注,治疗两周,观察两组治疗前、后的超敏C反应蛋白(hs-CRP)、尿微量白蛋白及肌酐变化,并在3个月后复查尿微量白蛋白与尿肌酐.结果 经过两周的治疗,治疗组的hs-CRP从(3.92±4.56) mg/L下降至(2.24±2.49) mg/L,差异有统计学意义(t=2.803,P<0.05),尿微量白蛋白从(127.18±76.91) mg/L下降至(84.50±122.87) mg/L,差异有统计学意义(t=2.501,P<0.05),尿微量白蛋白与尿肌酐的比值从(28.95±30.49) mg/mmol下降至(13.76±20.83) mg/mmol,差异有统计学意义(t=3.616,P<0.05).而对照组差异则无统计学意义.但3个月后两组的尿微量白蛋白及其与尿肌酐的比值与治疗前相比差异均无统计学意义(P均> 0.05).结论 α硫辛酸治疗后短期内能够减少DN患者的尿微量白蛋白,但其能否长期减少DN患者的尿微量白蛋白有待进一步研究.%Objective To investigate the clinical application of alpha lipoic acid on early diabetic nephropathy(DN).Methods Seventy patients with early diabetic nephropathy were randomly divided into two groups.Patients in control group were treated with regular glycemic control methods,while patients in treatment group were received alpha lipoic acid 300 mg static drop treatment for two weeks beside regular treatment.High sensitivity C reaction protein,microalbuminuria and urine creatinine were measured before and after the treatment.Microalbuminuria and urine creatinine were re-measured three months later.Results At the end of two weeks treatment,the levels of high sensitivity C reaction protein in the treatment group decreased from (3.92 ± 4.56) mg/L to (2.24 ± 2.49) mg/L,and there was significant difference (t =2.803,P < 0

  8. The Combination of N-Acetyl Cysteine, Alpha-Lipoic Acid, and Bromelain Shows High Anti-Inflammatory Properties in Novel In Vivo and In Vitro Models of Endometriosis

    Directory of Open Access Journals (Sweden)

    C. Agostinis

    2015-01-01

    Full Text Available To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs and on endothelial cells isolated from normal uterus (UtMECs. We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory “marker” VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.

  9. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling.

    Science.gov (United States)

    Packer, Lester; Cadenas, Enrique

    2011-01-01

    The role of R-α-lipoic acid as a cofactor (lipoyllysine) in mitochondrial energy metabolism is well established. Lipoic acid non-covalently bound and exogenously administered to cells or supplemented in the diet is a potent modulator of the cell's redox status. The diversity of beneficial effects of lipoic acid in a variety of tissues can be mechanistically viewed in terms of thiol/disulfide exchange reactions that modulate the environment's redox and energy status. Lipoic acid-driven thiol/disulfide exchange reactions appear critical for the modulation of proteins involved in cell signaling and transcription factors. This review emphasizes the effects of lipoic acid on PI3K and AMPK signaling and related transcriptional pathways that are integrated by PGC-1α, a critical regulator of energy homoestasis. The effects of lipoic acid on the neuronal energy-redox axis are largely reviewed in terms of their outcomes for aging and age-related neurodegenerative diseases.

  10. Nonlinear Optical Properties of Au-Nanoparticles Conjugated with Lipoic Acid in Water

    Science.gov (United States)

    Trejo-Durán, M.; Cornejo-Monroy, D.; Alvarado-Méndez, E.; Olivares-Vargas, A.; Castano, V. M.

    2014-08-01

    Gold nanoparticles were chemically conjugated with lipoic acid to control their optical properties. Z-scan and other optical techniques were used to characterize the non-linear behavior of the resulting nanostructured materials. The results show that the nonlinearity is of thermal origin, which can be controlled by the use of lipoic acid as well as other organic molecules conjugated onto metal nanoparticles. In particular, the presence of lipoic acid increases n_2 and dn/dT.

  11. Effect of alpha lipoic acid co-administration on structural and immunohistochemical changes in subcutaneous tissue of anterior abdominal wall of adult male albino rat in response to polypropylene mesh implantation.

    Science.gov (United States)

    Mazroa, Shireen A; Asker, Samar A; Asker, Waleed; Abd Ellatif, Mohamed

    2015-06-01

    Polypropylene mesh is commonly used in the treatment of abdominal hernia. Different approaches were addressed to improve their tissue integration and consequently reduce long-term complications. This study aimed to investigate the effect of alpha-lipoic acid (ALA) co-administration on structural and immunohistochemical (IHC) changes in the subcutaneous tissues of the anterior abdominal wall of the adult rat in response to polypropylene mesh implantation. Forty adult male albino rats were divided into: group I (control), group II (receiving ALA), group III (polypropylene mesh implantation) and group IV (mesh implantation + ALA co-administration). After 4 weeks, subcutaneous tissue samples were prepared for light microscopy and IHC study of CD34 as a marker for angiogenesis. In groups I and II rats, positive CD34 expression was demonstrated by IHC reaction, localized to endothelial cells lining small blood vessels. Group III showed an excess inflammatory reaction, deposition of both regular and irregularly arranged collagen fibres around mesh pores and few elastic fibres. CD34-positive was detected not only in cells lining small blood vessels but also in other cells scattered in the connective tissue indicating angiogenesis. In group IV, ALA co-administration resulted in less inflammatory reaction, regular collagen deposition, enhanced elastic fibres synthesis and a significant increase in CD34-positive cells and small blood vessels reflecting improved angiogenesis. ALA co-administration with polypropylene mesh implantation controlled the inflammatory reaction, helped regular collagen deposition, enhanced elastic fibres synthesis and improved angiogenesis in the subcutaneous tissue of anterior abdominal wall of adult albino rats, suggesting a possible role of ALA in optimizing mesh integration in subcutaneous tissue.

  12. Prostaglandin E1 Combined with Alpha Lipoic Acid and Mecobalamin in Treating First Diagnosis of Type 2 Diabetes Peripheral Neuropathy%前列地尔联合α-硫辛酸及甲钴胺治疗初诊2型糖尿病周围神经病变疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨昕; 刘志民

    2016-01-01

    Objective To observe the clinical efficacy of prostaglandin E1, alpha lipoic acid and mecobalamin on first diagnosis of type 2 diabetes peripheral neuropathy. Methods 350 patients with first diagnosis of type 2 diabetes peripheral neuropathy were selected and randomly divided into the prostaglandin E1+alpha lipoic acid+mecobalamin group 71 cases;prostaglandin E1+alpha lipoic acid group 69 cases; alpha lipoic acid+mecobalamin group 72 cases; prostaglandin E1+mecobalamin group 68 cases; control group 70 cases. The nerve conduction velocity , sensory symptoms and overall clinical efficacy were compared before and after treatment among the 5 groups. Results The nerve conduction velocity and the clinical symptoms of feeling in the 4 treatment groups improved compared with before treatment ( P < 0. 01 ); compared with the control group, the 4 treatment groups improved significantly better, the difference between groups was statistically significant ( P < 0. 01 ) , and the prostaglandin E1+alpha lipoic acid+mecobalamin group improved the most significantly. Conclusion On the basis of blood sugar control, comprehensive therapy of prostaglandin E1, alpha lipoic acid and mecobalamin is the key in treating and improving diabetic peripheral neuropathy.%目的:观察初诊2型糖尿病周围神经病变患者应用前列地尔、α-硫辛酸及甲钴胺的临床疗效。方法选取初诊2型糖尿病周围神经病变患者350例,随机分为前列地尔+α-硫辛酸+甲钴胺组71例,前列地尔+α-硫辛酸组69例,α-硫辛酸+甲钴胺组72例,前列地尔+甲钴胺组68例,对照组70例,比较5组患者治疗前后的神经传导速度及临床感觉症状和总体疗效。结果4个治疗组患者的神经传导速度及临床感觉症状均较治疗前有显著改善( P<0.01);与对照组相比,4个治疗组的改善程度显著优于对照组,组间差异有统计学意义( P<0.01),尤以前列地尔+α-硫辛酸

  13. α-硫辛酸对育肥猪生产性能和抗氧化功能的影响%Effects of dietary alpha-lipoic acid on growth performance and anti-oxidative ability in finishing pigs

    Institute of Scientific and Technical Information of China (English)

    汪善锋; 周光宏; 高峰; 徐孝宙

    2013-01-01

    研究日粮中添加α-硫辛酸对肥育猪生产性能和抗氧化功能的影响.对照组饲喂基础日粮,试验组在基础日粮中分别添加300、600和900 mg/kg的旷硫辛酸,试验期28 d.结果表明:与对照组相比,添加600、900 mg/kgα-硫辛酸降低了平均日增重(P<0.05)和平均日采食量(P<0.01),而各组料重比差异均不显著(P>0.05);900mg/kgα-硫辛酸组总抗氧化能力增加显著(P<0.05),谷胱甘肽过氧化物酶活性极显著增强(P<0.01).α-硫辛酸添加组血清中丙二醛含量均显著降低(P<0.05).α-硫辛酸的适宜添加水平为600 mg/kg.%The 28 d experiment was conducted to evaluate the effects of dietary alpha-lipoic acid (LA) on growth performance and anti-oxidative ability in finishing pigs.The feed diets were containing 0,300,600 and 900 mg/kg LA,respectively.The results showed that addition of 600 or 900 mg/kg LA decreased ADG (P<0.05) and AFI (P<0.01),compared with the control group.FCR was not affected by dietary LA content(P>0.05).Dietary 900 mg/kg LA significantly increased TAOC(P<0.05) and GSH-Px(P<0.01).Pigs fed LA had lower MDA(P<0.05).The optimal amount of LA addition in the dietary of finishing pigs was 600 mg/kg.

  14. Effects of two antioxidants; α-lipoic acid and fisetin against diabetic cataract in mice.

    Science.gov (United States)

    Kan, Emrah; Kiliçkan, Elif; Ayar, Ahmet; Çolak, Ramis

    2015-02-01

    The purpose of this study was to determine whether α-lipoic acid and fisetin have protective effects against cataract in a streptozotocin-induced experimental cataract model. Twenty-eight male BALB/C mice were made diabetic by the intraperitoneal administration of streptozotocin (200 mg/kg). Three weeks after induction of diabetes, mice were divided randomly into 4 groups in which each group contained 7 mice; fisetin-treated group (group 1), α-lipoic acid-treated group (group 2), fisetin placebo group (group 3), α-lipoic acid placebo group (group 4). Fisetin and α-lipoic acid were administered intraperitoneally weekly for 5 weeks. Cataract development was assessed at the end of 8 weeks by slit lamp examination, and cataract formation was graded using a scale. All groups developed at least grade 1 cataract formation. In the fisetin-treated group, the cataract stages were significantly lower than in the placebo group (p = 0.02). In the α-lipoic acid-treated group, the cataract stages were lower than in the placebo group but it did not reach to a significant value. Both fisetin and α-lipoic acid had a protective effect on cataract development in a streptozotocin-induced experimental cataract model. The protective effect of fisetin appears as though more effective than α-lipoic acid.

  15. 度洛西汀联合硫辛酸治疗糖尿病周围神经病变性疼痛的疗效观察%Therapeutic effect analysis of duloxetine hydrochloride combined with alpha-lipoic acid in treatment of diabetic peripheral neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    沈柿芬; 郭道骝

    2016-01-01

    目的:探讨度洛西汀联合硫辛酸治疗糖尿病周围神经病变性疼痛的有效性及安全性。方法:将78例糖尿病周围神经病变性疼痛患者随机分为两组,西汀组口服度洛西汀,联合组口服度洛西汀和静脉滴注硫辛酸,比较两组疗效。结果:两组治疗后正中神经感觉传导速度(median nerve conduction velocity,MNCV)、腓总神经感觉传导速度(phil nerve conduction velocity,PNCV)、尺神经感觉传导速度(ulnar nerve conduction velocity,UNCV)均显著提高(P0.05);两组治疗前、治疗8周后胆固醇(TC)、甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、血肌酐(SCr)指标水平均无显著性变化(P>0.05)。结论:度洛西汀联合硫辛酸治疗糖尿病周围神经病变性疼痛,能有效改善患者神经功能,减轻疼痛症状,且安全可靠。%Objective:By comparing duloxetine combination with alpha-lipoic acid and duloxetine in the therapeutic effect of painful diabetic neuropathy, to explore the efficacy and safety of duloxetine combination with alpha-lipoic acid treatment on diabetic peripheral neuropathic pain (DPNP) is optimal.Methods:78 cases with painful diabetic neuropathy of type 2 diabetes were recruited from our department and randomly divided into two groups, which were duloxetine in combination with alpha-lipoic acid group and duloxetine treatment group.Results: Compared to baseline, median nerve sensory conduction velocity (MNCV), Phil nerve conduction velocity (PNCV) and ulnar nerve conduction velocity (UNCV) of both groups were better (P0.05). Before treatment, no statistically signiifcant differences were detected in total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (SCr) between two groups (P>0.05).Conclusion:Duloxetine hydrochloride combined with alpha-lipoic acid has a good

  16. Analysis of Reaction between α-Lipoic Acid and 2-Chloro-1-methylquinolinium Tetrafluoroborate Used as a Precolumn Derivatization Technique in Chromatographic Determination of α-Lipoic Acid.

    Science.gov (United States)

    Godlewska, Magdalena; Odachowska, Angelika; Turkowicz, Monika; Karpinska, Joanna

    2015-01-01

    The present study offers results of analysis concerning the course of reaction between reduced α-lipoic acid (LA) and 2-chloro-1-methylquinolinium tetrafluoroborate (CMQT). In water environments, the reaction between CMQT and hydrophilic thiols proceeds very rapidly and the resultant products are stable. For the described analysis, optimum reaction conditions, such as concentration of the reducing agent, environment pH, and concentration of the reagent were carefully selected. The spectrophotometric assay was carried out measuring absorbance at λ = 348 nm (i.e., the spectral band of the obtained reaction product). Furthermore, the calibration curve of lipoic acid was registered. It was concluded that the Lambert-Beer law was observed within the range 1-10 μmol L(-1). Later, the reaction between LA and CMQT was used as precolumn derivatization in a chromatographic determination of the lipoic acid in the range 2.5-50 μmol L(-1). Practical applicability of the designed methods was evaluated by determining lipoic acid in Revitanerv pharmaceutical preparation which contains 300 mg LA in a single capsule. The error of the determination did not exceed 0.5% in relation to the declared value.

  17. Analysis of Reaction between α-Lipoic Acid and 2-Chloro-1-methylquinolinium Tetrafluoroborate Used as a Precolumn Derivatization Technique in Chromatographic Determination of α-Lipoic Acid

    Directory of Open Access Journals (Sweden)

    Magdalena Godlewska

    2015-01-01

    Full Text Available The present study offers results of analysis concerning the course of reaction between reduced α-lipoic acid (LA and 2-chloro-1-methylquinolinium tetrafluoroborate (CMQT. In water environments, the reaction between CMQT and hydrophilic thiols proceeds very rapidly and the resultant products are stable. For the described analysis, optimum reaction conditions, such as concentration of the reducing agent, environment pH, and concentration of the reagent were carefully selected. The spectrophotometric assay was carried out measuring absorbance at λ=348 nm (i.e., the spectral band of the obtained reaction product. Furthermore, the calibration curve of lipoic acid was registered. It was concluded that the Lambert-Beer law was observed within the range 1–10 μmol L−1. Later, the reaction between LA and CMQT was used as precolumn derivatization in a chromatographic determination of the lipoic acid in the range 2.5–50 μmol L−1. Practical applicability of the designed methods was evaluated by determining lipoic acid in Revitanerv pharmaceutical preparation which contains 300 mg LA in a single capsule. The error of the determination did not exceed 0.5% in relation to the declared value.

  18. Effect of α-lipoic Acid on Hemolytic Activity of Iranian Vipera Lebetina Venom

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    Amoozgari, Z. (MSc

    2015-05-01

    Full Text Available Background and Objective: Snake venom is a complex of several toxic elements and enzymes. It has the agents with the ability to destroy cellular and subcellular membrane and to bring about hemolysis of red blood cells (RBC. Two types of direct and indirect hemolytic activity are known in snake venom in that phospholipase A2 is responsible for the indirect lysis. The aim of this study was to investigate the effect of α-lipoic acid on hemolytic activity of Iranian Vipera Lebetina venom. Material and Methods: Protein concentration of the crude venom of Vipera Lebetina was determined using bovine serum albumin as a standard. Direct hemolytic activity of venom was determined by using the Human RBC and Indirect hemolytic activity was assayed on RBC in the presence of egg yolk. Then, α-lipoic acid with different concentrations in 100 mM Tris-HCL buffer was applied and its effect on hemolysis of RBC was studied. Results: direct hemolytic activity on RBC was not observed while its indirect activity was detected to be increased proportional to different concentration of α-lipoic acid. The range of indirect hemolysis was increased up to 60% by 60µm α-lipoic acid. Conclusion: Not only has α-lipoic acid no inhibitory effects on the hemolytic activity of Iranian Vipera Lebetina venom but also has the positive effects on it.

  19. Effects of alpha lipoic acid on diabetic retinopathy and serum levels of serum asymmetric dimethylarginine and oxidative stress%α-硫辛酸治疗糖尿病视网膜病变的疗效观察及其机制探讨

    Institute of Scientific and Technical Information of China (English)

    尹清风; 马海军; 陈雪辉; 曹萌; 白立炜; 张清贵

    2014-01-01

    目的 观察α-硫辛酸治疗糖尿病变视网膜病变(DR)的治疗效果,并探讨其疗效产生的可能机制,为α-硫辛酸临床治疗DR提供实验依据.方法 纳入75例DR患者,按随机数字表法分为对照组和治疗组:对照组进行正规降血糖、血压等综合治疗,治疗组在上述治疗基础上每天加用α-硫辛酸注射液600 mg+0.9%氯化钠注射液250 ml避光静脉滴注治疗,共4周;治疗前后两组患者均进行眼底荧光血管造影检查及视力检查;高效液相色谱法检测两组患者治疗前后血清非对称性二甲基精氨酸(ADMA)水平,并检测血清脂质过氧化产物丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性以反映体内氧化应激.结果 与对照组比较,α-硫辛酸治疗的DR患者视力明显改善,对眼部病变改善的总有效率显著升高(84.21% vs40.54%,X2=15.28,P<0.01);血中内源性一氧化氮合酶抑制物ADMA[(0.32 ±0.13)μmol/L vs(0.51 ±0.26) μmol/L,P<0.05]及MDA[(3.22 ±0.90) nmol/L vs (5.13 ±0.42) nmol/ml,P<0.05]水平明显降低,抗氧化酶SOD[(72.68±1.31) U/ml vs (53.16±1.54) U/ml,P<0.05]活性升高.结论 α-硫辛酸治疗DR患者有一定疗效,主要改善DR患者的眼部病变和视力,其机制可能与抗氧化和降低血清内源性一氧化氮合酶(NOS)抑制物ADMA水平有关.%Objective To investigate the effects of alpha lipoic acid on patients with diabetic retinopathy (DR),explore the possible mechanisms,and provide experimental evidence for the treatment of DR with lipoic acid.Methods Totally 75 DR patients were randomly divided into control group and treatment group.Patients in control group received the standard hypoglycemic treatment,antihypertensive therapy,and other comprehensive treatment.Patients from the treatment group were treated with alpha lipoic acid 600 mg + 250 ml 0.9% sodium chloride injection additionally,avoiding light intravenous therapy,for a total of 4 weeks.Before and after treatment

  20. Efficacy of ultrashort wave electrotherapy combined with alpha-lipoic acid on diabetic peripheral neuropathy%超短波电疗联合α-硫辛酸治疗糖尿病周围神经病变的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    郭妮; 王为民; 颜新; 苏庆建; 韦美娟; 杨丽

    2015-01-01

    目的:观察超短波电疗联合α-硫辛酸治疗糖尿病周围神经病变的临床疗效。方法60例糖尿病周围神经病变( DPN)患者,随机分为治疗组和对照组,每组30例,治疗组采用超短波电疗联合α-硫辛酸抗氧化剂治疗;对照组采用常规治疗。观察两组治疗前后空腹血糖、餐后2 h血糖,血清超氧化物歧化酶( SOD)活性。结果两组患者治疗后血糖均得到理想控制。治疗后治疗组SOD水平明显升高,振动觉阈值明显下降,且明显低于对照组治疗后水平( P<0.05)。治疗后,治疗组显效26例(86.7%),好转3例(11.1%),无效1例(2.2%);对照组显效16例(53.3%),好转10例(33.3%),无效4例(13.3%)。治疗组疗效优于对照组(P<0.01)。结论采用超短波电疗联合α-硫辛酸抗氧化剂治疗糖尿病周围神经病变取得良好效果。%Objective To investigate the efficacy of ultrashort wave electrotherapy combined with alpha-lipoic acid on the treatment of diabetic peripheral neuropathy( DPN) .Methods Sixty patients with DPN were randomly divided into treatment group and control group, with 30 cases in each group.The treatment group was given ultrashort wave electrotherapy combined with alpha-lipoic acid antioxidant,while the control group was given routine treatment.The levels of fast blood glucose(FBG) and 2-hour postprandial blood glucose(2hPBG) as well as the activity of serum superoxide dismutase( SOD) were detected in two groups before and after treatment.Results The patients in two groups achieved ideal blood glucose control after treatment.The level of SOD increased significantly while the vibration perception threshold(VPT) decreased significantly in the treatment group after treatment in contrast with those before treatment,VPT of treatment group was significantly lower than that of control group after treatment(P<0.05).After treatment

  1. Effect of α-lipoic acid combined with conventional therapy on serum markers of early diabetic nephropathy patients

    Institute of Scientific and Technical Information of China (English)

    Xin-Dong Jin; Xiang-Dong Liu; Xi-Ping Niu

    2015-01-01

    Objective: To study the effect ofα-lipoic acid combined with conventional therapy on serum markers of early diabetic nephropathy patients.Methods: Patients with early diabetic nephropathy treated in our hospital from May 2012 to May 2014 were chosen for study and randomly divided into two groups. Lipoic acid group received α-lipoic acid combined with conventional drug therapy; conventional group received conventional drug therapy. Then renal function, oxidative stress, podocyte injury degree, mitochondrial fusion and fission protein contents of both groups were compared.Results:(1) renal function and oxidative stress indicators: serum CysC, RBP, 8-OHdG, NT, MDA and F2-aisoprostanes contents of lipoic acid group showed a decreasing trend; (2) podocyte injury indicators: serum Nephrin, Podocin, Desmin and CD2AP contents of lipoic acid group showed a significantly increasing trend; (3) mitochondrial indicators: serum Mfs1, Mfs2 and Opa1 contents of lipoic acid group significantly increased; Fis1, Mff and GDAP1 contents significantly decreased.Conclusion:α-lipoic acid combined with conventional therapy is helpful to improve renal function, relieve oxidative stress and protect podocyte structure and mitochondrial function; it’s an ideal method in treating early diabetic nephropathy.

  2. Protective Roles of α-lipoic Acid in Rat Model of Mitochondrial DNA4834bp Deletion in Inner Ear

    Institute of Scientific and Technical Information of China (English)

    彭炜; 胡钰娟; 钟毅; 陈蓓; 孙宇; 杨阳; 孔维佳

    2010-01-01

    The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and...

  3. Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Sivaprasad, R.; Nagaraj, M.; Varalakshmi, P. [Department of Medical Biochemistry, University of Madras (Taramani), Chennai 600 113 (India)

    2002-08-01

    The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-{alpha}-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p) and DMSA (20 mg/kg body weight per day i.p) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of {gamma}-glutamyl transferase and N-acetyl {beta}-D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione-S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell. (orig.)

  4. Effects of Alpha-lipoic Acid on Congnitive Function in Lacunar Infarction Patients with Diabetes Mellitu%α-硫辛酸对腔隙性脑梗死伴糖尿病患者认知功能的影响

    Institute of Scientific and Technical Information of China (English)

    丛文东; 吴达荣; 曾佳; 高展

    2013-01-01

      目的:观察腔隙性脑梗死伴糖尿病患者的认知功能损害特点,并探讨α‐硫辛酸对其认知功能的影响。方法:伴有糖尿病的腔隙性脑梗死患者60例,随机分配在 A 组(30例,每天静脉使用α‐硫辛酸)和B组(30例,一般治疗)中,对照组(30例)选用健康体检人群。使用蒙特利尔认知评估量表(MOCA)分别对两组患者在发病后3天、3个月进行认知功能评估,并分别与正常对照组进行比较。结果:在脑梗死发病后3天,两组患者均出现视空间与执行功能、命名、延迟记忆、注意力和计算能力、语言、定向功能障碍,总分与对照组相比差异有显著性。在发病后3个月,使用硫辛酸组各项评分较一般治疗组高,总分及注意力、视空间与执行功能、定向力差异有统计学意义。结论:在伴有糖尿病的腔隙性脑梗死患者急性期认知损害广泛,α‐硫辛酸对认知功能具有保护作用。%  Objective:To explore the characters of cognitive dysfunction for lacunar infarction (L I) with diabetes mellitus and the protective effects of alpha‐lipoic acid .Methods :A total of 64 LI patients with dia‐betes mellitus randomly divided into 2 groups .Patients of group 1 (n=30) were treated with alphalipoic acid .Patients of group 2(n=30) were assigned conventional therapy .The cognitive function of patients were evaluated with Montreal Cognitive Assessment (MOCA) at 3days and 3months after attack .An additional control group consisted of age‐matched healthy (n=30) .Results:Compared with controls ,significant differ‐ence was found on the memory ,name ,language ,orientation ,attention ,executive function ,visuospatial and visuo‐constructive function at 3 days .Most cognitive domains were improved at 3 months of group 1 ,scores of general MoCA ,attention ,visuospatial and visuo‐constructive function and orientation were higher than those of

  5. Lipoic Acid Gold Nanoparticles Functionalized with Organic Compounds as Bioactive Materials

    Science.gov (United States)

    Turcu, Ioana; Zarafu, Irina; Popa, Marcela; Chifiriuc, Mariana Carmen; Bleotu, Coralia; Culita, Daniela; Ghica, Corneliu; Ionita, Petre

    2017-01-01

    Water soluble gold nanoparticles protected by lipoic acid were obtained and further functionalized by standard coupling reaction with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether. Derivatives of lipoic acid with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether were also obtained and characterized. All these were tested for their antimicrobial activity, as well as for their influence on mammalian cell viability and cellular cycle. In all cases a decreased antimicrobial activity of the obtained bioactive nanoparticles was observed as compared with the organic compounds, proving that a possible inactivation of the bioactive groups could occur during functionalization. However, both the gold nanoparticles as well as the functionalized bioactive nanosystems proved to be biocompatible at concentrations lower than 50 µg/mL, as revealed by the cellular viability and cell cycle assay, demonstrating their potential for the development of novel antimicrobial agents.

  6. Oxidative modification of lipoic acid by HNE in Alzheimer disease brain

    Directory of Open Access Journals (Sweden)

    Sarita S. Hardas

    2013-01-01

    Full Text Available Alzheimer disease (AD is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP and intracellular neurofibrillary tangles (NFTs. The major component of SP is amyloid β-peptide (Aβ, which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE. HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH were measured in AD and control brains. Additionally, LADH activities were measured after in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidative dysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.

  7. Alpha-lipoic acid inhibits mitochondrial oxidative stress in the rat skeletal muscle with chronic hypoxia exposure%α-硫辛酸抑制慢性低氧大鼠骨骼肌线粒体的氧化应激**

    Institute of Scientific and Technical Information of China (English)

    肖频; 庞奕辉; 彭朋; 薄海

    2013-01-01

    BACKGROUND: α-lipoic acid is named as “nature antioxidant” and “mitochondrial nutrition”. But it is unclear whether α-lipoic acid can be used to protect skeletal muscle with chronic hypoxia exposure, as wel as the relative mechanism. OBJECTIVE: To observe the effect of α-lipoic acid on the antioxidant enzymes and oxidative stress in rat skeletal muscle with chronic hypoxia exposure, and to investigate the relative signaling pathway of α-lipoic acid. METHODS: Thirty-six Sprague Dawley rats were randomly divided into three groups: normoxia control group, hypoxia control group, and hypoxia+α-lipoic acid group. Rats in the hypoxia control group were subjected to hypoxia exposure in normobaric hypoxic tent with 11.3% oxygen concentration. Rats in the hypoxia+α-lipoic acid group were induced by adding α-lipoic acid (0.25%) in the normal diet. Al the interventions were lasted for 4 weeks. RESULTS AND CONCLUSION: α-lipoic acid in hypoxia could markedly enhance the mitochondrial Sirtuin-3 expression, improve the mitochondrial adenosine triphosphate synthesis activity and membrane potential, up-regulate the mitochondrial state 3 respiratory rate, respiratory control ratio and ratio of phosphorus to oxygen, down-regulate the mitochondrial state 4 respiratory rate and promote and up-regulate the activity of mitochondrial antioxidant enzymes such as manganese superoxide dismutase, glutathione peroxidase and catalase, thus inhibiting mitochondrial H2O2 generation rate and reducing mitochondrial malondialdehyde level. The results indicated that α-lipoic acid could improve the efficiency of energy metabolism of chronic hypoxia skeletal muscle mitochondria and inhibit reactive oxygen generation, and it could inhibit the oxidative stress through improving antioxidant enzyme activity of mitochondria. The protection mechanism of α-lipoic acid on hypoxia skeletal muscle mitochondria may be related to the increasing of mitochondrial state 3 respiratory rate.%  背

  8. Alleviative effects of α-lipoic acid supplementation on acute heat stress-induced thermal panting and the level of plasma nonesterified fatty acids in hypothyroid broiler chickens.

    Science.gov (United States)

    Hamano, Y

    2012-01-01

    1. The present study was conducted to examine the effects of α-lipoic acid on hypothyroidism-induced negative growth performance and whether α-lipoic acid alleviates acute heat stress in relation to hypothyroid status. 2. Female broiler chickens (14 d-old) were fed diets supplemented with α-lipoic acid (100 mg/kg) and an antithyroid substance, propylthiouracil (200 mg/kg), for 20 d under thermoneutral conditions (25°C). At 42 d of age, chickens were exposed to a high ambient temperature (36°C, 60% RH) for 4 h. 3. Under the thermoneutral condition, propylthiouracil administration decreased feed efficiency and concomitantly increased adipose tissue and thyroid gland weights. Plasma nonesterified fatty acids and triacylglycerol were also increased by propylthiouracil administration. However, α-lipoic acid supplementation did not affect the hypothyroidism-induced effects. 4. In hypothyroid chickens, the rise in respiratory rate induced by heat exposure was greatly inhibited by α-lipoic acid administration at 1 h, but this effect had disappeared at 4 h. In addition, a similar inhibitory effect on the concentrations of plasma nonesterified fatty acids was subsequently observed at 4 h. 5. Therefore, the present study suggested that α-lipoic acid alleviates acute heat stress if chickens are in a hypothyroid status.

  9. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  10. Effects of combined lipoic acid and pyridoxine on albuminuria, advanced glycation end-products, and blood pressure in diabetic nephropathy.

    Science.gov (United States)

    Noori, Nazanin; Tabibi, Hadi; Hosseinpanah, Farhad; Hedayati, Mehdi; Nafar, Mohsen

    2013-01-01

    This study was designed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycation end-products, nitric oxide (NO), and endothelin-1 in patients with diabetic nephropathy. Thirty-four patients were randomly assigned to either a supplement group or a placebo group. The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks, whereas the placebo group received corresponding placebos. Urinary albumin, serum malondialdehyde (MDA), and systolic blood pressure decreased significantly in the supplement group compared to the placebo group (p blood pressure. The present study indicates that combined administration of lipoic acid and pyridoxine improves albuminuria in patients with diabetic nephropathy by reducing oxidative stress, advanced glycation end-products, and systolic blood pressure. The reduction in microalbuminuria may be of benefit in retarding the progression of diabetic nephropathy.

  11. Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance

    Science.gov (United States)

    2011-01-01

    Obese subjects with impaired glucose tolerance (IGT) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease. This randomised controlled investigation was designed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT. All data were collected from 24 obese (BMI ≥ 30 kg/m2) IGT patients. Following participant randomisation into two groups, fasting venous blood samples were obtained at baseline, and before and following intervention. The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65% HRmax for 30 minutes a day, 5 days per week, while ingesting 1 gram per day of α-lipoic acid for 12 weeks. The second group consisted of 12 participants who completed the same 12 week control phase, but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only (no exercise). The main findings show a comparatively greater rate of low density lipoprotein (LDL) oxidation in the group consisting of α-lipoic acid only (p 0.05). These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise, suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances, but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD. However, when α-lipoic acid is combined with exercise, this atherogenic effect is abolished. PMID:22107734

  12. Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload

    Directory of Open Access Journals (Sweden)

    Yasser F. Ali

    2015-01-01

    Full Text Available This work was aimed to study the protective role of α-lipoic acid against the oxidative damage of induced iron overload. Iron (Fe overload is a complication of the treatment, by chronic transfusion, of a number of genetic diseases associated with inadequate red cell production (anemias and of other genetic diseases that lead to excessive iron absorption from the diet. Male rats were injected ip with 5 mg/kg body weight ferrous sulfate for 50 days. The animals were injected ip with α-lipoic acid 20 mg per kg body weight for 21 days. Serum iron, Total Iron Binding Capacity (TIBC, Malonyldialdehyde (MDA, Electron paramagnetic resonance (EPR spectroscopy, UV-visible absorption spectrum of hemoglobin and osmotic fragility were studied. Results showed significant increase in serum iron, total iron binding capacity, and malonyldialdehyde levels in iron-loaded rats. Treatment with lipoic acid (LA resulted in decreasing serum iron and TIBC levels by 47%and 29% respectively. At the same time the lipoic acid decreased the level of the MDA in liver, brain and plasma by 54%, 42% and 74% respectively. Also LA diminished the effect of iron-induced free radicals on erythrocyte membrane integrity; it decreased the elevated average osmotic fragility and decreased the elevated rate of hemolysis. Results from UV-visible spectrophotometric measurement of hemoglobin revealed that no oxidative changes of hemoglobin occurred in iron-loaded rats. EPR spectra showed increased in non-heme ferric ions Fe+3 and free radicals in iron-loaded rats. Whereas the injection of the lipoic acid leads to decreased in such toxic result. In conclusion, these observations suggested that lipoic acid might be a beneficial antioxidant that can be effective for limiting damage from oxidative stress of iron overload.

  13. Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance

    Directory of Open Access Journals (Sweden)

    McNeilly Andrea M

    2011-11-01

    Full Text Available Abstract Obese subjects with impaired glucose tolerance (IGT are more susceptible than healthy individuals to oxidative stress and cardiovascular disease. This randomised controlled investigation was designed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT. All data were collected from 24 obese (BMI ≥ 30 kg/m2 IGT patients. Following participant randomisation into two groups, fasting venous blood samples were obtained at baseline, and before and following intervention. The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65% HRmax for 30 minutes a day, 5 days per week, while ingesting 1 gram per day of α-lipoic acid for 12 weeks. The second group consisted of 12 participants who completed the same 12 week control phase, but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only (no exercise. The main findings show a comparatively greater rate of low density lipoprotein (LDL oxidation in the group consisting of α-lipoic acid only (p p p p p > 0.05. These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise, suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances, but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD. However, when α-lipoic acid is combined with exercise, this atherogenic effect is abolished.

  14. Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance.

    Science.gov (United States)

    McNeilly, Andrea M; Davison, Gareth W; Murphy, Marie H; Nadeem, Nida; Trinick, Tom; Duly, Ellie; Novials, Anna; McEneny, Jane

    2011-11-22

    Obese subjects with impaired glucose tolerance (IGT) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease. This randomised controlled investigation was designed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT. All data were collected from 24 obese (BMI ≥ 30 kg/m2) IGT patients. Following participant randomisation into two groups, fasting venous blood samples were obtained at baseline, and before and following intervention. The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65% HRmax for 30 minutes a day, 5 days per week, while ingesting 1 gram per day of α-lipoic acid for 12 weeks. The second group consisted of 12 participants who completed the same 12 week control phase, but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only (no exercise). The main findings show a comparatively greater rate of low density lipoprotein (LDL) oxidation in the group consisting of α-lipoic acid only (p decreased following exercise training (p 0.05). These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise, suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances, but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD. However, when α-lipoic acid is combined with exercise, this atherogenic effect is abolished.

  15. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria.

    Science.gov (United States)

    Zee, Tiffany; Bose, Neelanjan; Zee, Jarcy; Beck, Jennifer N; Yang, See; Parihar, Jaspreet; Yang, Min; Damodar, Sruthi; Hall, David; O'Leary, Monique N; Ramanathan, Arvind; Gerona, Roy R; Killilea, David W; Chi, Thomas; Tischfield, Jay; Sahota, Amrik; Kahn, Arnold; Stoller, Marshall L; Kapahi, Pankaj

    2017-03-01

    Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1(-/-) mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

  16. The photochemistry of lipoic acid: photoionization and observation of a triplet excited state of a disulfide.

    Science.gov (United States)

    Bucher, Götz; Lu, Changyuan; Sander, Wolfram

    2005-12-09

    Under short-wavelength UV irradiation, lipoic acid (LipSS) and its reduced form, dihydrolipoic acid (DHLA), undergo photoionization processes through a bi- or monophotonic pathway. After ionization, the LipSS radical cation (LipSS*+) and radical anion (LipSS*-) are generated. LipSS*- can be converted to equimolar amounts of LipSS and DHLA through second-order decay. Triplet acetone can be quenched by LipSS and DHLA with a rate close to the diffusion-controlled limit. The mechanism was further confirmed by continuous irradiation experiments. When LipSS is directly irradiated with UVA light, the first excited triplet state of LipSS is observed, with a lifetime tau=75 ns. Characteristic reactions include triplet energy transfer to oxygen and beta-carotene and addition to isoprene. The lifetime of triplet LipSS is also shortened by addition of water and methanol.

  17. Effects of α-lipoic acid supplementation on sexual difference of growth performance, heat exposure-induced metabolic response and lipid peroxidation of raw meat in broiler chickens.

    Science.gov (United States)

    Hamano, Y

    2014-01-01

    1. The effects of α-lipoic acid administration on sexual differences in growth performance, heat exposure-induced metabolic response and lipid peroxidation of raw meat in broiler chickens were studied. 2. Two-week-old male and female broiler chicks were divided into two groups each, as a 2 × 2 factorial arrangement. Half the birds were fed on a diet supplemented with α-lipoic acid (100 mg/kg) and half on a control diet. All groups were reared to 6 weeks of age at 25°C and, thereafter, exposed to 33°C for 8 h per day for 3 d. 3. Under thermo-neutral conditions, α-lipoic acid decreased feed consumption and body weight gain of male chickens. However, the feed conversion rate and tissue mass of breast muscle and abdominal fat were unchanged. 4. In plasma metabolites, α-lipoic acid increased the molar ratio of non-esterified fatty acids to free glycerol, regardless of sex and heat exposure. A decrease in β-hydroxybutyrate was observed in the α-lipoic acid-fed male chickens. In the heat-exposed chickens, α-lipoic acid lowered the molar ratio of plasma lactate to pyruvate in relation to the enhanced concentrations of plasma pyruvate. However, no sexual difference was observed. 5. The value of thiobarbituric acid reactive substances in breast meat of heat-stressed chickens that was refrigerated for 3 or 7 d was higher in males than in females. An antioxidative effect of α-lipoic acid was observed in the meat of male chickens. 6. The present study suggests that the α-lipoic acid-inducing fatty acid metabolism and antioxidative effect persisted during the heat stress, even though a sexual difference in the responsiveness was seen in broiler chickens.

  18. Observation Curative Effect on Alprostadil Combine With Alpha Lipoic in Treatment of Diabetic Foot%前列地尔联合α-硫辛酸治疗糖尿病足疗效观察

    Institute of Scientific and Technical Information of China (English)

    吴昌南

    2015-01-01

    Objective To explore the clinical effect of alprostadil combined with alpha lipoic in the treatment of diabetic foot. Methods Selected 90 cases with diabetic foot in our hospital as the research object, randomly divided into control group and treatment group, 45 cases in each group. Treatment group were treated with alprostadil combined with alpha lipoic treatment, the control group using the traditional treatment methods. Results The total effective rate of the treatment group was higher than that of the control group, P<0.05, had difference statistically significance. Conclusion Alprostadil combined with alpha lipoic acid in the treatment of diabetic foot can improve the treatment efifciency and the symptoms of patients with diabetic foot.%目的:探讨前列地尔联合α-硫辛酸治疗糖尿病足的临床疗效。方法选取我院收治的90例糖尿病足患者为研究对象,随机分成对照组和治疗组,每组各45例。治疗组采用前列地尔联合α-硫辛酸治疗,对照组采用传统的治疗方法。结果治疗组总有效率高于对照组, P<0.05,差异具有统计学意义。结论前列地尔联合α-硫辛酸治疗糖尿病足,可以有效地提高治疗的总有效率,改善糖尿病足患者的症状。

  19. 硫辛酸对糖尿病肾病大鼠足细胞氧化应激的保护作用%Protce tive effect of the alpha-lipoic acid on oix datvi e stress in podocytes of rats with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    刘洁; 王红杰; 侯明辉; 张晶; 张海松

    2015-01-01

    [Abts ract] Objective To investigate the protective effect of alpha-lipoic acid ( ALA ) on oxidative stress in the podocytes of rats with diabetic nephropathy.Methods After the rat models with diabetic nephropathy were successfully established,the 10 rats were randomly selected as diabetic nephropathy group (group B), the other 10 rats were regarded as ALA intervention group (group C),at the sime time, 10 normal rats were served as control group (group A).The animals were sacrificed at th end of 13weeks ,and the renal tissues specimens were harvested .The expression levels of nephrin and podocin were detected by Western Blot and immunohistochemistry.The contents of malondialdehyde ( MDA) in renal tissues were measured by thiobarbituric acid (TAB) method and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase ( GSH-PX) in renal tissues were detected by xanthine oxidase and dithio-2 nitrobenzoic acid method,respectively. Resu lts As compared with those in group A,the concentrations of MDA in group B were significantly increased, however, the acticities of T-SOD ,GSH-PX and the expression levels of nephrin, podocin were significantly decreased ( P <0.05).As compared with those in group B, the concentrations of MDA were obviously decereased, but the acticities of TS-OD ,GSH-PX and the expression levels of nephrin, podocin were significantly increased in group C ( P <0.05).Conclusion ALA can inhibit the apoptosis of podocyte, reduce the urine protein and delay the pathogenesis and development of diabetic nephropathy through antioxidative stress effects.%目的:探讨硫辛酸对糖尿病肾病(DN)大鼠足细胞氧化应激的保护作用。方法制备糖尿病肾病( DN)大鼠模型,成模后随机选取10只作为 DN组( B组),10只作为硫辛酸干预组( C组),并设立正常对照组(A组)。实验共13周,于第13周末收集各组大鼠肾组织标本,分别应用硫代巴比妥酸( TAB)法、黄嘌

  20. Lipoic acid and redox status in barley plants subjected to salinity and elevated CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Lopez, U.; Robredo, A.; Mena-Petite, A.; Munoz-Rueda, A. (Univ. del Pais Vasco/EHU, Dept. de Biologia Vegetal y Ecologia, Bilbao (Spain)); Lacuesta, M. (Univ. del Pais Vasco/EHU, Dept. de Biologia Vegetal y Ecologia, Vitoria-Gasteiz (Spain)); Sgherri, C.; Navari-Izzo, F. (Univ. di Pisa, Dipartimento di Chimica e Biotecnologie Agrarie, Pisa (Italy))

    2010-02-15

    Future environmental conditions will include elevated concentrations of salt in the soil and an elevated concentration of CO{sub 2}in the atmosphere. Because these environmental changes will likely affect reactive oxygen species (ROS) formation and cellular antioxidant metabolism in opposite ways, we analyzed changes in cellular H{sub 2}O{sub 2} and non-enzymatic antioxidant metabolite [lipoic acid (LA), ascorbate (ASA), glutathione (GSH)] content induced by salt stress (0, 80, 160 or 240 mM NaCl) under ambient (350 mumol mol-1) or elevated (700 mumol mol-1) CO{sub 2}concentrations in two barley cultivars (Hordeum vulgare L.) that differ in sensitivity to salinity (cv. Alpha is more sensitive than cv. Iranis). Under non-salinized conditions, elevated CO{sub 2}increased LA content, while ASA and GSH content decreased. Under salinized conditions and ambient CO{sub 2}, ASA increased, while GSH and LA decreased. At 240 mM NaCl, H{sub 2}O{sub 2} increased in Alpha and decreased in Iranis. When salt stress was imposed at elevated CO{sub 2}, less oxidative stress and lower increases in ASA were detected, while LA was constitutively higher. The decrease in oxidative stress could have been because of less ROS formation or to a higher constitutive LA level, which might have improved regulation of ASA and GSH reductions. Iranis had a greater capacity to synthesize ASA de novo and had higher constitutive LA content than did Alpha. Therefore, we conclude that elevated CO{sub 2}protects barley cultivars against oxidative damage. However, the magnitude of the positive effect is cultivar specific. (author)

  1. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory, E-mail: Tory.Hagen@oregonstate.edu [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  2. Preventive effect of α-lipoic acid on prepulse inhibition deficits in a juvenile two-hit model of schizophrenia.

    Science.gov (United States)

    Deslauriers, J; Racine, W; Sarret, P; Grignon, S

    2014-07-11

    Some pathophysiological models of schizophrenia posit that prenatal inflammation sensitizes the developing brain to second insults in early life and enhances brain vulnerability, thereby increasing the risk of developing the disorder during adulthood. We previously developed a two-hit animal model, based on the well-established prenatal immune challenge with poly-inosinic/cytidylic acid (polyI:C), followed by juvenile restraint stress (RS). We observed an additive disruption of prepulse inhibition (PPI) of acoustic startle in juvenile mice submitted to both insults. Previous studies have also reported that oxidative stress is associated with pathophysiological mechanisms of psychiatric disorders, including schizophrenia. We report here that PPI disruption in our two-hit animal model of schizophrenia is associated with an increase in oxidative stress. These findings led us to assess whether α-lipoic acid, an antioxidant, can prevent both increase in oxidative status and PPI deficits in our juvenile in vivo model of schizophrenia. In the offspring submitted to prenatal injection of polyI:C and to RS, treatment with α-lipoic acid prevented the development of PPI deficits 24h after the last period of RS. α-Lipoic acid also improved PPI performance in control mice. The reversal effect of α-lipoic acid pretreatment on these behavioral alterations was further accompanied by a normalization of the associated oxidative status and dopaminergic and GABAergic abnormalities in the prefrontal cortex. Based on our double insult paradigm, these results support the hypothesis that oxidative stress plays an important role in the development of PPI deficits, a well-known behavior associated with schizophrenia. These findings form the basis of future studies aiming to unravel mechanistic insights of the putative role of antioxidants in the treatment of schizophrenia, especially during the prodromal stage.

  3. Self-Assembly of Pyridine-Modified Lipoic Acid Derivatives on Gold and Their Interaction with Thyroxine (T4

    Directory of Open Access Journals (Sweden)

    Pierangelo Metrangolo

    2013-02-01

    Full Text Available Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4. Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR. The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated. Two ligands, a 4-pyridyl and a bis(2-hydroxyethyl derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4. The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer. Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used. More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis(2-hydroxy-ethyl derivatives of lipoic acid were combined in the imprinted layer.

  4. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

    Directory of Open Access Journals (Sweden)

    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  5. BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid.

    Science.gov (United States)

    Findlay, John A; Hamilton, David L; Ashford, Michael L J

    2015-01-01

    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  6. Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Naoko Ikuta

    2016-06-01

    Full Text Available R-α-lipoic acid (R-LA is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD, yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA.

  7. Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers.

    Science.gov (United States)

    Ikuta, Naoko; Okamoto, Hinako; Furune, Takahiro; Uekaji, Yukiko; Terao, Keiji; Uchida, Ryota; Iwamoto, Kosuke; Miyajima, Atsushi; Hirota, Takashi; Sakamoto, Norihiro

    2016-06-15

    R-α-lipoic acid (R-LA) is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD), yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA.

  8. Gold Nanoparticles and Lipoic Acid as a Novel Anti-Inflammatory Treatment for Autism, A Hypothesis

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2012-01-01

    Full Text Available Autism is a neurodevelopment disorder. Its aetiology and pathophysiology are not clearly known. However, mitochondria may play a significant role at least in some cases of autism. There is no therapeutic approach for autism. Moreover, there are only few Food and Drug Administration (FDA-approved medications for autism. Therefore, providing novel therapeutic approaches are highly required. Oxidative stress is suggested as an important factor in the aetiology of autism. Already some interventions targeting oxidative stress in autism are suggested.This article reviews evidence about the possible role of gold nanoparticles and lipoic acid (LA as anti-inflammatory agents. It mentions some evidence about the possible role of oxidative stress. Then, the role of gold nanoparticles and LA for the management of autism is discussed.According to the above-mentioned evidence, it is hypothesised that gold nanoparticles and LA may reduce neuro-inflammation in autism.Controlled experimental studies are needed to test whether gold nanoparticles plus LA enhance antioxidative stress system leading to the improvement of autism clinical symptoms.

  9. Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy

    Science.gov (United States)

    Xu, Longquan; Hiller, Sylvia; Simington, Stephen; Nickeleit, Volker; Maeda, Nobuyo; James, Leighton R.; Yi, Xianwen

    2016-01-01

    Oxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN) but outcomes of many clinical trials are controversial. To define the role of antioxidants in kidney protection during the development of diabetic nephropathy, we have generated a novel genetic antioxidant mouse model with over- or under-expression of lipoic acid synthase gene (Lias). These models have been mated with Ins2Akita/+ mice, a type I diabetic mouse model. We compare the major pathologic changes and oxidative stress status in two new strains of the mice with controls. Our results show that Ins2Akita/+ mice with under-expressed Lias gene, exhibit higher oxidative stress and more severe DN features (albuminuria, glomerular basement membrane thickening and mesangial matrix expansion). In contrast, Ins2Akita/+ mice with highly-expressed Lias gene display lower oxidative stress and less DN pathologic changes. Our study demonstrates that strengthening endogenous antioxidant capacity could be an effective strategy for prevention and treatment of DN. PMID:27706190

  10. Dietary Lipoic Acid Influences Antioxidant Capability and Oxidative Status of Broilers

    Directory of Open Access Journals (Sweden)

    Yong-Ze Jie

    2011-11-01

    Full Text Available The effects of lipoic acid (LA on the antioxidant status of broilers were investigated. Birds (1 day old were randomly assigned to four groups and fed corn-soybean diets supplemented with 0, 100, 200, 300 mg/kg LA, respectively. The feeding program included a starter diet from 1 to 21 days of age and a grower diet from 22 to 42 days of age. Serum, liver and muscle samples were collected at 42 days of age. For antioxidant enzymes, superoxide dismutase (SOD and glutathione peroxidase (GSH-Px activity in serum, liver and breast muscle significantly increased in chickens fed with LA. The concentration of malondiadehyde (MDA, an indicator of lipid peroxidation, was significantly lower in serum, liver and leg muscle in birds that received LA than in the control group. Treatments with LA significantly increased glutathione (GSH content in liver and increased α-tocopherol content in leg muscle as compared to the control. These results indicate that dietary supplementation with 300 mg/kg LA may enhance antioxidant capability and depress oxidative stress in broilers.

  11. Enzymatic hybridization of α-lipoic acid with bioactive compounds in ionic solvents.

    Science.gov (United States)

    Papadopoulou, Athena A; Katsoura, Maria H; Chatzikonstantinou, Alexandra; Kyriakou, Eleni; Polydera, Angeliki C; Tzakos, Andreas G; Stamatis, Haralambos

    2013-05-01

    The lipase-catalyzed molecular hybridization of α-lipoic acid (LA) with bioactive compounds pyridoxine, tyrosol and tyramine was performed in ionic solvents and deep eutectic solvents. The biocatalytic reactions were catalyzed by Candida antarctica lipase B immobilized onto various functionalized multi-walled carbon nanotubes (f-CNTs-CaLB), as well as by commercial Novozym 435. The use of f-CNTs-CaLB leads, in most cases, to higher conversion yields as compared to Novozym 435. The nature and ion composition of ionic solvents affect the performance of the biocatalytic process. The highest conversion yield was observed in (mtoa)NTf2. The high enzyme stability and the relatively low solubility of substrates in specific media account for the improved biocatalytic synthesis of molecular hybrids of LA. Principal component analysis was used to screen for potential lipoxygenase inhibitors. In vitro studies showed that the synthesized compounds exhibit up to 10-fold increased inhibitory activity on lipoxygenase mediated lipid peroxidation as compared to parent molecules.

  12. In Vivo Anti-inflammatory Activity of Lipoic Acid Derivatives in Mice 

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    Brunon Kwiecień

    2013-04-01

    Full Text Available Background: In mammals lipoic acid (LA and its reduced form dihydrolipoic acid (DHLA function as cofactors for multienzymatic complexes catalyzing the decarboxylation of α-ketoacids. Moreover, LA is used as a drug in a variety of diseases including inflammatory diseases. The aim of the study was to examine anti-inflammatory properties of LA metabolites.Material/methods:The present paper reports the chemical synthesis of 2,4-bismethylthio-butanoic acid (BMTBA and tetranor-dihydrolipoic acid (tetranor-DHLA. BMTBA is one of the biotransformation products of LA, while tetranor-DHLA is an analogue of DHLA. Structural identity of these compounds was confirmed by 1H NMR. These compounds were assessed for their anti-inflammatory activity in mice. For this purpose, the zymosan-induced peritonitis and the carrageenan-induced hind paw edema animal models were applied.Results/conclusions: The obtained results indicated that the early vascular permeability measured at 30 min of zymosan-induced peritonitis was significantly inhibited in groups receiving BMTBA (10, 30, 50 mg/kg. The early infiltration of neutrophils measured at 4 hours of zymosan-induced peritonitis was inhibited in the group receiving BMTBA (50 mg/kg and tetranor-DHLA (50 mg/kg. The results indicated that the increase in paw edema was significantly inhibited in the groups receiving BMTBA (50, 100 mg/kg and tetranor-DHLA (30, 50 mg/kg. In summary, the present studies clearly demonstrated that both BMTBA and tetranor-DHLA were able to act as anti-inflammatory agents. This is the first study examining in vivo the anti-inflammatory properties of LA metabolites.

  13. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade.

    Science.gov (United States)

    El-Gowelli, Hanan M; Saad, Evan I; Abdel-Galil, Abdel-Galil A; Ibrahim, Einas R

    2015-11-01

    In this work, α-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that α-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of α-lipoic acid (35 mg/kg ip) or cyclosporine (5mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-α (TNF-α). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of α-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-α. Unexpectedly, co-administration of α-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of α-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of α-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using α-lipoic acid/cyclosporine combination in ulcerative colitis patients.

  14. (R-(+-α-Lipoic acid protected NG108-15 cells against H2O2-induced cell death through PI3K-Akt/GSK-3β pathway and suppression of NF-κβ-cytokines

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    Kamarudin MNA

    2014-10-01

    Full Text Available Muhamad Noor Alfarizal Kamarudin, Nur Afiqah Mohd Raflee, Sharifah Salwa Syed Hussein, Jia Ye Lo, Hadi Supriady, Habsah Abdul KadirInstitute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer’s disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R-(+-alpha-lipoic acid (R-LA against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5–50 µM aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α. The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for

  15. Photoinduced interactions between oxidized and reduced lipoic acid and riboflavin (vitamin B2).

    Science.gov (United States)

    Lu, Changyuan; Bucher, Götz; Sander, Wolfram

    2004-01-23

    As a powerful natural antioxidant, lipoic acid (LipSS) and its reduced form dihydrolipoic acid (DHLA) exert significant antioxidant activities in vivo and in vitro by deactivation of reactive oxygen and nitrogen species (ROS and RNS). In this study the riboflavin (RF, vitamin B2) sensitized UVA and visible-light irradiation of LipSS and DHLA was studied employing continuous irradiation, fluorescence spectroscopy, and laser flash photolysis (LFP). Our results indicate that LipSS and DHLA quench both the singlet state (1RF*) and the triplet state (3RF*) of RF by electron transfer to produce the riboflavin semiquinone radical (RFH.) and the radical cation of LipSS and DHLA, respectively. The radical cation of DHLA is rapidly deprotonated twice to yield a reducing species, the radical anion of LipSS (LipSS.-). When D2O was used as solvent, it was confirmed that the reaction of LipSS with 3RF* consists of a simple electron-transfer step, while loss of hydrogen occurs in the case of DHLA oxidation. Due to the strong absorption of RFH. and the riboflavin ground state, the absorption of the radical cation and the radical anion of LipSS can not be observed directly by LFP. N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and N,N,N',N'-tetramethyl benzidine (TMB) were added as probes to the system. In the case of LipSS, the addition resulted in the formation of the radical cation of TMPD or TMB by quenching of the LipSS radical cation. If DHLA is the reducing substrate, no formation of probe radical cation is observed. This confirms that LipSS.- is produced by riboflavin photosensitization, and that there is no oxidizing species produced after DHLA oxidization.

  16. [Evaluation of the actiom of lipoic acid in ischemia and hypertension].

    Science.gov (United States)

    Borets, V M; Kishkovich, V P; Lis, M A; Butkevich, N D; Kalkun, D P

    1977-01-01

    A total of 203 patients, 48 -- with ischemic and 155 -- with hypertensive disease in the 11A and 11B stages, were examined. The effect of lipoic acid (LA) was assessed on the ground of the dynamics in the clinical picture of the patients, some vitamins allowance figures and the activity of a number of enzymes in leucocytes, erythrocytes and in the blood serum. The LA was administered in the form of tablets, in a dose of 75 mg per day, for 10 dyas. As controls served 90 patients with ischemic and hypertensive diseases. Investigations showed the LA to have but a little influence on the clinical picture of the disease, raising somewhat the beta-lipoproteids level in patients with hypertensive and ischemic disease, irrespective of their age, and increasing the level of free fatty acids in patients over 50, forcing it down in those below 50. An age-specific effect of the LA on the blood proteinic spectrum was disclosed, viz. in patients below 55 it increased the proportion of albumins and reduced that of gamma-globulins, whereas in those aged above 55 reverse picture was in evidence. In the young LA had the tendency of bringing down the coagulating activity of the blood; whereas disaggregation of thrombocytes changed not depending upon the age, but on the form of the affection, decreasing in patients with hypertensive disease and remaining unchanged in those with ischemic heart disease. The LA helped normalize the thiamine metabolism in the organism and that of the thiamine-diphosphate containing enzymes with concurrently disturbed utilization of riboflavin in the examined patients.

  17. A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

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    Giuseppe Derosa

    2016-10-01

    Full Text Available The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG, post-prandial-glucose (PPG, glycated hemoglobin (HbA1c, fasting plasma insulin (FPI, HOMA-index (HOMA-IR, lipid profile, high sensitivity C-reactive protein (Hs-CRP, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, malondialdehyde (MDA. There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

  18. Microwave-Assisted Resolution of α-Lipoic Acid Catalyzed by an Ionic Liquid Co-Lyophilized Lipase

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    Ning Liu

    2015-05-01

    Full Text Available The combination of the ionic liquid co-lyophilized lipase and microwave irradiation was used to improve enzyme performance in enantioselective esterification of α-lipoic acid. Effects of various reaction conditions on enzyme activity and enantioselectivity were investigated. Under optimal condition, the highest enantioselectivity (E = 41.2 was observed with a high enzyme activity (178.1 μmol/h/mg when using the ionic liquid co-lyophilized lipase with microwave assistance. Furthermore, the ionic liquid co-lyophilized lipase exhibited excellent reusability under low power microwave.

  19. α-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction.

    Science.gov (United States)

    Inman, Denise M; Lambert, Wendi S; Calkins, David J; Horner, Philip J

    2013-01-01

    Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense of long-term testing, few studies have modeled antioxidant therapy for prevention of neurodegeneration. We investigated the contribution of oxidative stress to the pathogenesis of glaucoma in the DBA/2J mouse model of glaucoma. Similar to other neurodegenerative diseases, we observed lipid peroxidation and upregulation of oxidative stress-related mRNA and protein in DBA/2J retina. To test the role of oxidative stress in disease progression, we chose to deliver the naturally occurring, antioxidant α-lipoic acid (ALA) to DBA/2J mice in their diet. We used two paradigms for ALA delivery: an intervention paradigm in which DBA/2J mice at 6 months of age received ALA in order to intervene in glaucoma development, and a prevention paradigm in which DBA/2J mice were raised on a diet supplemented with ALA, with the goal of preventing glaucoma development. At 10 and 12 months of age (after 4 and 11 months of dietary ALA respectively), we measured changes in genes and proteins related to oxidative stress, retinal ganglion cell (RGC) number, axon transport, and axon number and integrity. Both ALA treatment paradigms showed increased antioxidant gene and protein expression, increased protection of RGCs and improved retrograde transport compared to control. Measures of lipid peroxidation, protein nitrosylation, and DNA oxidation in retina verified decreased oxidative stress in the prevention and intervention paradigms. These data demonstrate the utility of dietary therapy for reducing oxidative stress and improving RGC survival in glaucoma.

  20. Effects of Lipoic Acid on Immune Function, the Antioxidant Defense System, and Inflammation-Related Genes Expression of Broiler Chickens Fed Aflatoxin Contaminated Diets

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    Yan Li

    2014-04-01

    Full Text Available This study was designed to evaluate the effect of low level of Aflatoxin B1 (AFB1 on oxidative stress, immune reaction and inflammation response and the possible ameliorating effects of dietary alpha-lipoic acid (α-LA in broilers. Birds were randomly allocated into three groups and assigned to receive different diets: basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1 for three weeks. The results showed that the serum levels of malondialdehyde, tumor necrosis factor alpha (TNFα and interferon gamma (IFNγ in the AFB1-treated group were significantly increased than the control group. In addition, the increased expressions of interleukin 6 (IL6, TNFα and IFNγ were observed in birds exposed to the AFB1-contaminated diet. These degenerative changes were inhibited by α-LA-supplement. The activities of total superoxide dismutase and glutathione peroxidase, the levels of humoral immunity, and the expressions of nuclear factor-κB p65 and heme oxygenase-1, however, were not affected by AFB1. The results suggest that α-LA alleviates AFB1 induced oxidative stress and immune changes and modulates the inflammatory response at least partly through changes in the expression of proinflammatory cytokines of spleen such as IL6 and TNFα in broiler chickens.

  1. Effects of Lipoic Acid on Immune Function, the Antioxidant Defense System, and Inflammation-Related Genes Expression of Broiler Chickens Fed Aflatoxin Contaminated Diets

    Science.gov (United States)

    Li, Yan; Ma, Qiu-Gang; Zhao, Li-Hong; Wei, Hua; Duan, Guo-Xiang; Zhang, Jian-Yun; Ji, Cheng

    2014-01-01

    This study was designed to evaluate the effect of low level of Aflatoxin B1 (AFB1) on oxidative stress, immune reaction and inflammation response and the possible ameliorating effects of dietary alpha-lipoic acid (α-LA) in broilers. Birds were randomly allocated into three groups and assigned to receive different diets: basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1 for three weeks. The results showed that the serum levels of malondialdehyde, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) in the AFB1-treated group were significantly increased than the control group. In addition, the increased expressions of interleukin 6 (IL6), TNFα and IFNγ were observed in birds exposed to the AFB1-contaminated diet. These degenerative changes were inhibited by α-LA-supplement. The activities of total superoxide dismutase and glutathione peroxidase, the levels of humoral immunity, and the expressions of nuclear factor-κB p65 and heme oxygenase-1, however, were not affected by AFB1. The results suggest that α-LA alleviates AFB1 induced oxidative stress and immune changes and modulates the inflammatory response at least partly through changes in the expression of proinflammatory cytokines of spleen such as IL6 and TNFα in broiler chickens. PMID:24699046

  2. Effects of lipoic acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets.

    Science.gov (United States)

    Li, Yan; Ma, Qiu-Gang; Zhao, Li-Hong; Wei, Hua; Duan, Guo-Xiang; Zhang, Jian-Yun; Ji, Cheng

    2014-04-02

    This study was designed to evaluate the effect of low level of Aflatoxin B1 (AFB1) on oxidative stress, immune reaction and inflammation response and the possible ameliorating effects of dietary alpha-lipoic acid (α-LA) in broilers. Birds were randomly allocated into three groups and assigned to receive different diets: basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1 for three weeks. The results showed that the serum levels of malondialdehyde, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) in the AFB1-treated group were significantly increased than the control group. In addition, the increased expressions of interleukin 6 (IL6), TNFα and IFNγ were observed in birds exposed to the AFB1-contaminated diet. These degenerative changes were inhibited by α-LA-supplement. The activities of total superoxide dismutase and glutathione peroxidase, the levels of humoral immunity, and the expressions of nuclear factor-κB p65 and heme oxygenase-1, however, were not affected by AFB1. The results suggest that α-LA alleviates AFB1 induced oxidative stress and immune changes and modulates the inflammatory response at least partly through changes in the expression of proinflammatory cytokines of spleen such as IL6 and TNFα in broiler chickens.

  3. The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury

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    Deguan Li

    2016-06-01

    Full Text Available Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS. The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA, which was synthesized from melatonin and α-lipoic acid, against radiation-induced hematopoietic injury. MLA administration significantly enhanced the survival rate of mice after 7.2 Gy total body irradiation. The results showed that MLA not only markedly increased the numbers and clonogenic potential of hematopoietic cells but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, MLA decreased the levels of ROS in hematopoietic cells by inhibiting NOX4 expression. These data demonstrate that MLA prevents radiation-induced hematopoietic syndrome by increasing the number and function of and by inhibiting DNA damage and ROS production in hematopoietic cells. These data suggest MLA is beneficial for the protection of radiation injuries.

  4. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Sancheti, Harsh; Akopian, Garnik; Yin, Fei; Brinton, Roberta D; Walsh, John P; Cadenas, Enrique

    2013-01-01

    Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits) and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) that shows progression of pathology as a function of age; two age groups: 6 months (young) and 12 months (old) were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O) and long term potentiation (LTP) (measured by electrophysiology). Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  5. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

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    Harsh Sancheti

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD that shows progression of pathology as a function of age; two age groups: 6 months (young and 12 months (old were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O and long term potentiation (LTP (measured by electrophysiology. Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  6. Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

    Science.gov (United States)

    Moura, Fabiana Andréa; de Andrade, Kívia Queiroz; de Araújo, Orlando Roberto Pimentel; Santos, Juliana Célia de Farias

    2016-01-01

    Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day−1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage. PMID:27957238

  7. Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

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    Fabiana Andréa Moura

    2016-01-01

    Full Text Available Lipoic acid (LA and N-acetylcysteine (NAC are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC. This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS (2% w/v. LA and/or NAC (100 mg·kg·day−1, each were given, once a day, in the diet, in a pretreatment phase (7 days and during UC induction (5 days. Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®. A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2, malondialdehyde (MDA levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage.

  8. The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress.

    Science.gov (United States)

    Skibska, Beata; Goraca, Anna

    2015-01-01

    Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

  9. Binding of lipoic acid induces conformational change and appearance of a new binding site in methylglyoxal modified serum albumin.

    Science.gov (United States)

    Suji, George; Khedkar, Santosh A; Singh, Sreelekha K; Kishore, Nand; Coutinho, Evans C; Bhor, Vikrant M; Sivakami, S

    2008-06-01

    The binding of lipoic acid (LA), to methylglyoxal (MG) modified BSA was studied using isothermal titration calorimetry in combination with enzyme kinetics and molecular modelling. The binding of LA to BSA was sequential with two sites, one with higher binding constant and another comparatively lower. In contrast the modified protein showed three sequential binding sites with a reduction in affinity at the high affinity binding site by a factor of 10. CD results show appreciable changes in conformation of the modified protein as a result of binding to LA. The inhibition of esterase like activity of BSA by LA revealed that it binds to site II in domain III of BSA. The pH dependence of esterase activity of native BSA indicated a catalytic group with a pK(a) = 7.9 +/- 0.1, assigned to Tyr411 with the conjugate base stabilised by interaction with Arg410. Upon modification by MG, this pK(a) increased to 8.13. A complex obtained by docking of LA to BSA and BSA in which Arg410 is modified to hydroimidazolone showed that the long hydrocarbon chain of lipoic acid sits in a cavity different from the one observed for unmodified BSA. The molecular electrostatic potential showed that the modification of Arg410 reduced the positive electrostatic potential around the protein-binding site. Thus it can be concluded that the modification of BSA by MG resulted in altered ligand binding characteristics due to changes in the internal geometry and electrostatic potential at the binding site.

  10. α-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects.

    Science.gov (United States)

    Fernández-Galilea, Marta; Pérez-Matute, Patricia; Prieto-Hontoria, Pedro L; Houssier, Marianne; Burrell, María A; Langin, Dominique; Martínez, J Alfredo; Moreno-Aliaga, María J

    2015-03-01

    α-Lipoic acid (α-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of α-Lip on mitochondrial biogenesis and the acquirement of brown-like characteristics by subcutaneous adipocytes from overweight/obese subjects. Thus, fully differentiated human subcutaneous adipocytes were treated with α-Lip (100 and 250μM) for 24h for studies on mitochondrial content and morphology, mitochondrial DNA (mtDNA) copy number, fatty acid oxidation enzymes and brown/beige characteristic genes. The involvement of the Sirtuin1/Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (SIRT1/PGC-1α) pathway was also evaluated. Our results showed that α-Lip increased mitochondrial content in cultured human adipocytes as revealed by electron microscopy and by mitotracker green labeling. Moreover, an enhancement in mtDNA content was observed. This increase was accompanied by an up-regulation of SIRT1 protein levels, a decrease in PGC-1α acetylation and up-regulation of Nuclear respiratory factor 1 (Nrf1) and Mitochondrial transcription factor (Tfam) transcription factors. Enhanced oxygen consumption and fatty acid oxidation enzymes, Carnitine palmitoyl transferase 1 and Acyl-coenzyme A oxidase (CPT-1 and ACOX) were also observed. Mitochondria from α-Lip-treated adipocytes exhibited some morphological characteristics of brown mitochondria, and α-Lip also induced up-regulation of some brown/beige adipocytes markers such as cell death-inducing DFFA-like effector a (Cidea) and T-box 1 (Tbx1). Moreover, α-Lip up-regulated PR domain containing 16 (Prdm16) mRNA levels in treated adipocytes. Therefore, our study suggests the ability of α-Lip to promote mitochondrial biogenesis and brown-like remodeling in cultured white subcutaneous adipocytes from overweight/obese donors.

  11. Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer's disease: a 13C NMR study.

    Science.gov (United States)

    Sancheti, Harsh; Kanamori, Keiko; Patil, Ishan; Díaz Brinton, Roberta; Ross, Brian D; Cadenas, Enrique

    2014-02-01

    Alzheimer's disease is an age-related neurodegenerative disease characterized by deterioration of cognition and loss of memory. Several clinical studies have shown Alzheimer's disease to be associated with disturbances in glucose metabolism and the subsequent tricarboxylic acid (TCA) cycle-related metabolites like glutamate (Glu), glutamine (Gln), and N-acetylaspartate (NAA). These metabolites have been viewed as biomarkers by (a) assisting early diagnosis of Alzheimer's disease and (b) evaluating the efficacy of a treatment regimen. In this study, 13-month-old triple transgenic mice (a mouse model of Alzheimer's disease (3xTg-AD)) were given intravenous infusion of [1-(13)C]glucose followed by an ex vivo (13)C NMR to determine the concentrations of (13)C-labeled isotopomers of Glu, Gln, aspartate (Asp), GABA, myo-inositol, and NAA. Total ((12)C+(13)C) Glu, Gln, and Asp were quantified by high-performance liquid chromatography to calculate enrichment. Furthermore, we examined the effects of lipoic acid in modulating these metabolites, based on its previously established insulin mimetic effects. Total (13)C labeling and percent enrichment decreased by ∼50% in the 3xTg-AD mice. This hypometabolism was partially or completely restored by lipoic acid feeding. The ability of lipoic acid to restore glucose metabolism and subsequent TCA cycle-related metabolites further substantiates its role in overcoming the hypometabolic state inherent in early stages of Alzheimer's disease.

  12. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells

    OpenAIRE

    Salinthone, Sonemany; Schillace, Robynn V.; Marracci, Gail H.; Bourdette, Dennis N.; Carr, Daniel W.

    2008-01-01

    The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells ...

  13. Protective effects of alpha lipoic acid on diabetic skeletal myopathy by attenuation mitochondria-dependent cell apoptosis%高血糖致骨骼肌细胞凋亡机制及α-硫辛酸保护作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    张秋梅; 李春君; 张景云; 李明珍; 于德民

    2011-01-01

    目的 探讨高血糖导致骨骼肌细胞凋亡的机制以及抗氧化剂α-硫辛酸的保护作用.方法 将30只雄性Wistar大鼠完全随机分为正常对照组(10只)、糖尿病组(8只)和α-硫辛酸组(8只),对后2组大鼠采用一次性尾静脉注射链脲佐菌素(STZ)45 mg/kg体重制备糖尿病大鼠模型,正常对照组尾静脉注射柠檬酸钠缓冲液,α-硫辛酸组大鼠每天腹腔注射α-硫辛酸0.033 ml/g,糖尿病组注射0.3ml的缓冲液,于α-硫辛酸注射后12周处死动物,处死前测量体重、血糖,苏木素-伊红染色和Masson染色观察骨骼肌的结构和纤维化,测定线粒体内外的细胞色素C、骨骼肌组织的天冬氨酸半胱氨酸(Caspase)-3.结果 糖尿病组骨骼肌纤维化明显增加,胶原含量明显高于正常对照组[(11.73±1.12)%比(3.12±0.32)%,P<0.01],α-硫辛酸组胶原含量(6.58±0.65)%明显低于糖尿病组[(1.73±1.12)%](P<0.05).与对照组比较,12周时糖尿病大鼠骨骼肌出现了明显的结构紊乱和纤维化,Caspase-3的蛋白质水平明显增加,线粒体内的细胞色素C减低,线粒体外的细胞色素C增加;α-硫辛酸治疗12周可以明显改善骨骼肌结构,减少纤维化,减少线粒体细胞色素C的释放,降低Caspase-3的蛋白质的表达,差异有统计学意义.结论 高血糖通过增加线粒体细胞色素C的释放导致骨骼肌细胞凋亡,α-硫辛酸通过减少线粒体细胞色素C的释放减少骨骼肌的细胞凋亡,防护糖尿病骨骼肌病变.%Objectives To explore the mechanisms of high glucose induced skeletal muscle cell apoptosis and observe the protection of antioxidant-lipoic acid(α-LA) on skeletal muscle. Methods Diabetic rat model was induced by a single dose of streptozotocin (45 mg/kg), randomly divided into 3 groups: normal control, diabetes control and α-LA. The structure and fibrosis of skeletal muscle were determined by HE and masson staining respectively. The protein level of cytochrome-c and

  14. Alfa-lipoic acid protects testosterone secretion pathway and sperm quality against 4-tert-octylphenol induced reproductive toxicity.

    Science.gov (United States)

    Othman, Azza I; El-Missiry, Mohamed A; Koriem, Khaled M; El-Sayed, Aml A

    2012-07-01

    The protective effect of α-lipoic acid (LA) (50 mg/kg bw) against 4-tert-octylphenol (OP) (50 mg/kg bw) induced reproductive toxicity in male rats was studied. LA was injected 1h prior to OP administration three times a week. OP caused significant increase in oxidative stress in hypothalamus and epididymal sperm, disturbed hormonal levels in serum, decreased sperm quality, increased DNA fragmentation and loss of 35 and 95 kDa proteins in sperm, as well as elevated proliferating index in testis. LA protected against oxidative stress through promoting the levels of glutathione and glutathione-S-transferase in hypothalamus and sperm. In addition, LA prevented the decrease in testosterone, dehydroepiandrosterone sulfate, 3β-hydroxysteroid dehydrogenase, and inhibited the elevations in sex-hormone-binding globulin levels and showed normal sperm quality. LA modulated proliferation of germ cell, protected against DNA fragmentation and maintained membrane protein organization in the sperm. In conclusion, LA normalized oxidative stress and protected testosterone synthesis pathway across hypothalamus-testicular axis and sperm quality indicating its defensive influence against OP-induced oxidative reproductive dysfunction in male rats.

  15. Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by α-lipoic acid in humans

    Institute of Scientific and Technical Information of China (English)

    Fritz Dünschede; Kirsten Erbes; Achim Kircher; Stefanie Westermann; Joachim Seifert; Arno Schad; Kempski Oliver; Alexandra K Kiemer; Junginger Theodor

    2006-01-01

    AIM:To evaluate the protective effects of preconditioning by α-lipoic acid (LA) in patients undergoing hepatic resection under inflow occlusion of the liver.METHODS:Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCl 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver.RESULTS:Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNELpositive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion.CONCLUSION:This is the first report on the potential for LA reducing ischemia/reperfusion injury (IRI) of the liver in humans who were undergoing liver surgery.Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.

  16. Proteomic and biochemical responses of canola (Brassica napus L.) exposed to salinity stress and exogenous lipoic acid.

    Science.gov (United States)

    Yıldız, Mustafa; Akçalı, Nermin; Terzi, Hakan

    2015-05-01

    To evaluate the mitigating effects of exogenous lipoic acid (LA) on NaCl toxicity, proteomic, biochemical and physiological changes were investigated in the leaves of canola (Brassica napus L.) seedlings. Salinity stress decreased the growth parameters and contents of ascorbate (AsA) and glutathione (GSH), and increased the contents of malondialdehyde (MDA), proline, cysteine and the activities of antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX). The foliar application of LA alleviated the toxic effects of salinity stress on canola seedlings and notably decreased MDA content and increased growth parameters, cysteine content, and activities of CAT and POD. In the proteomic analyses, total proteins from the leaves of control, LA, NaCl and NaCl+LA treated-seedlings were separated using two-dimensional gel electrophoresis (2-DE). A total of 28 proteins were differentially expressed. Of these, 21 proteins were successfully identified by MALDI-TOF/TOF MS. These proteins had functions related to photosynthesis, stress defense, energy metabolism, signal transduction, protein folding and stabilization indicating that LA might play important roles in salinity through the regulation of photosynthesis, stress defense and signal transduction related proteins. The proteomic findings have provided new insight to reveal the effect of LA on salinity stress for the first time.

  17. Lipoic acid and haloperidol-induced vacuous chewing movements: Implications for prophylactic antioxidant use in tardive dyskinesia.

    Science.gov (United States)

    Lister, Joshua; Andreazza, Ana C; Navaid, Bushra; Wilson, Virginia S; Teo, Celine; Nesarajah, Yasika; Wilson, Alan A; Nobrega, José N; Fletcher, Paul J; Remington, Gary

    2017-01-04

    Tardive dyskinesia (TD), a potentially irreversible antipsychotic (AP)-related movement disorder, is a risk with all currently available antipsychotics. AP-induced vacuous chewing movements (VCMs) in rats, a preclinical model of TD, can be attenuated by antioxidant-based treatments although there is a shortage of well-designed studies. Lipoic acid (LA) represents a candidate antioxidant for the treatment of oxidative stress-related nervous system disorders; accordingly, its effects on AP-induced VCMs and striatal oxidative stress were examined. Rats treated with haloperidol decanoate (HAL; 21mg/kg every 3weeks, IM) for 12weeks were concurrently treated with LA (10 or 20mg/kg, PO). VCMs were assessed weekly by a blinded rater, and locomotor activity was evaluated as were striatal lipid peroxidation markers and serum HAL levels. VCMs were decreased by the lower dose (nonsignificant), whereas a significant increase was recorded with the higher dose of LA. HAL decreased locomotor activity and this was unaffected by LA. Striatal malondialdehyde (MDA) levels in HAL-treated rats were reduced by both LA doses, while 4-hydroxynonenal (4-HNE) levels were predictive of final VCM scores (averaged across weeks 10-12). Study limitations include differences between antipsychotics in terms of oxidative stress, LA dosing, choice of biomarkers for lipid peroxidation, and generalizability to TD in humans. Collectively, current preclinical evidence does not support a "protective" role for antioxidants in preventing TD or its progression, although clinical evidence offers limited evidence supporting such an approach.

  18. Differential efficiency of simvastatin and lipoic acid treatments on Bothrops jararaca envenomation-induced acute kidney injury in mice.

    Science.gov (United States)

    Barone, Juliana Marton; Alponti, Rafaela Fadoni; Frezzatti, Rodrigo; Zambotti-Villela, Leonardo; Silveira, Paulo Flávio

    2011-01-01

    Snake bite accidents by Bothrops genus is an important public health issue in Brazil and one of its most serious complications is the acute kidney injury (AKI). Here we evaluated the effects of Bothrops jararaca venom (vBj) and the treatments with lipoic acid (LA) and simvastatin (SA) on renal function, aminopeptidase (AP) activities and renal redox status. Primordial events for establishment of AKI by vBj were hyperuricemia, hypercreatinemia, urinary hyperosmolality, renal oxidative stress and reduction of hematocrit and protein content in the membrane of renal cortex and medulla and in the plasma. In the renal cortex and medulla the changes caused by vBj in soluble and membrane-bound AP activities had a similar pattern. The beneficial effects of LA and SA on envenomed mice were similar on the hyperuricemia, renal oxidative stress and reduction of hematocrit. LA mitigated the hypercreatinemia, but exacerbated the urinary urea and creatinine, whereas SA mitigated the decrease of plasma urea, urinary hyperosmolality and hypercreatinuria induced by vBj. The beneficial effects of LA and especially of SA on renal effects of vBj open a new perspective for clinical investigations of these drugs as coadjuvant agents in the serotherapy of Bothrops envenomation.

  19. Effect of combination therapy consisting of enalapril, α-lipoic acid, and menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat.

    Science.gov (United States)

    Davidson, Eric P; Holmes, Amey; Coppey, Lawrence J; Yorek, Mark A

    2015-10-15

    We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or menhaden oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and menhaden oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and menhaden oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.

  20. Effect of hyperbaric oxygen combined withα-lipoic acid on neurological function and serum indexes of patients with diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    Yu Li; Ling Qi; Jun Li

    2016-01-01

    Objective:To analyze the effect of hyperbaric oxygen combined withα-lipoic acid on neurological function and serum indexes of patients with diabetic peripheral neuropathy. Methods:A total of 118 diabetic peripheral neuropathy patients who received treatment in our hospital were selected as research subjects, and according to the different clinical treatment they received, all included patients were divided into observation group 59 cases and control group 59 cases. Control group received conventional clinical treatment, and observation group received additional hyperbaric oxygen combined withα-lipoic acid treatment. Differences in nerve conduction velocity, gastrocnemius nerve threshold, illness-related factors, oxidative stress indicator values, and so on were compared between two groups after treatment.Results:MCV and SCV values of median nerve, ulnar nerve and tibial nerve of observation group after treatment were higher than those of control group (P<0.05); gastrocnemius nerve threshold of observation group after treatment were significantly lower than those of control group (P<0.05); serum CP and BDNF values of observation group after treatment were higher than those of control group while Cys-C, SDF-1α, HMGB1 and MBP values were lower than those of control group (P<0.05); serum MDA and NO values of observation group after treatment were lower than those of control group while SOD, CAT and GSH-Px values were higher than those of control group (P<0.05).Conclusions:Hyperbaric oxygen combined withα-lipoic acid is a good method to optimize the neurological function and improve overall illness of patients with diabetic peripheral neuropathy, and is expected to become a new way of inhibiting disease progression and improving disease outcome.

  1. Effect ofα-lipoic acid combined with mecobalamine therapy on urodynamics and oxidative damage of nerve in patients with diabetic neurogenic bladder

    Institute of Scientific and Technical Information of China (English)

    Ming-Bao Ye; Chang-Guo Du; Qun-Feng Yan; Jia-Mei Gui

    2016-01-01

    Objective:To analyze the effect ofα-lipoic acid combined with mecobalamine therapy on urodynamics and oxidative damage of nerve in patients with diabetic neurogenic bladder. Methods:A total of 78 patients with diabetic neurogenic bladder were randomly divided into observation group and control group (n=39), control group received conventional therapy and observation group received conventional therapy +α-lipoic acid combined with mecobalamine therapy. Before treatment and after one course of treatment, urodynamic indexes, peripheral nerve conduction latency time and serum indexes of two groups were detected respectively. Results: After one course of treatment, RUV, Pdet, FS, T and C value as well as ROS, MDA, SP, NPY and ChAT content of both groups were significantly lower than those before treatment, MFR value as well as GSH, SOD, BDNF and CNTF content was significantly higher than those before treatment, and the sensory conduction latency time of median nerve and ulnar nerve as well as motor conduction latency time of median nerve and peroneal nerve were shorter than those before treatment (P<0.05); RUV, Pdet, FS, T and C value as well as ROS, MDA, SP, NPY and ChAT content of observation group were significantly lower than those of control group, MFR value as well as GSH, SOD, BDNF and CNTF content was significantly higher than those of control group, and the sensory conduction latency time of median nerve and ulnar nerve as well as motor conduction latency time of median nerve and peroneal nerve were significantly shorter than those of control group (P<0.05).Conclusions:α-lipoic acid combined with mecobalamine therapy can optimize the urodynamics in patients with diabetic neurogenic bladder and also reduce the oxidative damage of nerve, and it is an effective solution for treatment of such disease.

  2. Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies.

    Science.gov (United States)

    Ikuta, Naoko; Endo, Takatsugu; Hosomi, Shota; Setou, Keita; Tanaka, Shiori; Ogawa, Noriko; Yamamoto, Hiromitsu; Mizukami, Tomoyuki; Arai, Shoji; Okuno, Masayuki; Takahashi, Kenji; Terao, Keiji; Matsugo, Seiichi

    2015-10-16

    R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S-S and C-S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring.

  3. Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study.

    Science.gov (United States)

    Keith, Dove J; Butler, Judy A; Bemer, Brett; Dixon, Brian; Johnson, Shawn; Garrard, Mary; Sudakin, Daniel L; Christensen, J Mark; Pereira, Cliff; Hagen, Tory M

    2012-09-01

    Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving elder health. Studies using old rats show that (R)-α-LA (R-LA) significantly increases low molecular weight antioxidants that otherwise decline with age. Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer. To address these discrepancies, a pilot study was performed to establish which form of LA is most effectively absorbed in older subjects relative to young volunteers. Young adults (average age=32 years) and older adults (average age=79 years) each received 500 mg of either R- or R,S-LA. Blood samples were collected for 3h after supplementation. After a washout period they were given the other chiral form of LA not originally ingested. Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA and area under the curve for the R-form of LA versus the racemic mixture. The elder subjects also demonstrated a reduced time to reach maximal plasma LA concentration following R-LA supplementation than for the racemic mixture. In contrast, young males had a tendency for increased bioavailability of R,S-LA. Overall, bioavailability for either LA isoform was much more variable between older subjects compared to young adults. Plasma glutathione levels were not altered during the sampling period. Thus subject age, and potential for varied response, should be considered when determining an LA supplementation regimen.

  4. Ameliorating effect of DL-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals.

    Science.gov (United States)

    Hussein, Asmma; Ahmed, Amany A E; Shouman, Samia A; Sharawy, Sabry

    2012-06-01

    Cisplatin is a potent chemotherapeutic agent with a wide range of activities. Nephrotoxicity and cardiotoxicity represent it's major complication upon clinical use. The present study was carried out to evaluate the possible protective effect of DL-α-lipoic acid (LA) against cisplatin-induced nephrotoxicity and cardiotoxicity. Different groups of rats (n = 10) were administered either saline (control), cisplatin (10 mg/kg, i.p.), LA (100 mg/kg, i.p.) or their combination (LA 30 min prior to cisplatin administration). Twenty-four hours later all animals were decapitated and sera were used for estimation of activities of urea (BUN), creatinine (Cr), lactate dehydrogenase (LDH), and creatine kinase (CK). Homogenates of the kidney and heart were used for estimation of oxidative stress markers (reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO)). Additionally, caspase-3 activities and DNA-fragmentation were investigated in renal tissues. The results showed that cisplatin produced significant elevation in serum activities of LDH, CK, BUN, and Cr and also induced significant elevation in the oxidative stress makers (MDA and NO) accompanied by significant reduction in GSH and SOD in both kidney and heart. The integrity of DNA was heavily damaged and caspase-3 was activated in renal tissues. The results emphasized nephrotoxicty and cardiotoxicity of cisplatin. On the other hand, prior administration of LA significantly attenuated the cisplatin-evoked disturbances in the above mentioned parameters and protected both kidney and heart tissues. The histopathological examination emphasized the obtained results. In conclusion, LA is suggested to be a potential candidate to ameliorate cisplatin-induced nephrotoxicity and cardiotoxicity without altering the antitumor efficacy of cisplatin.

  5. Study of the therapeutic effects of Lactobacillus and α-lipoic acid against dimethylnitrosamine-induced liver fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Khairy M.A. Zoheir

    2014-12-01

    Full Text Available Lactobacillus (LB and α-lipoic acid (ALA were investigated to compare their protective effects against dimethylnitrosamine (DMN-induced liver fibrosis in rats. Animals were either injected intraperitoneally with DMN to induce hepatic fibrosis, or were left untreated (negative control. For the DMN + LB and DMN + ALA treatment groups, at two weeks of DMN treatment LB or ALA was added to the feed and supplementation continued until the experimental endpoint at sixty days. At the study endpoint, expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, TGF-β1, COL1-α1 genes and the concentration of glutathione and malondialdehyde were measured in liver tissues, while GOT, GPT, and ALP concentrations were measured in blood. Body weights remained higher in NC and DMN + LB groups compared to DMN and DMN + ALA groups, while activity of GOT and GPT in serum was lower in DMN + LB and DMN + ALA groups compared to the DMN group. Compared to other treatment groups, in the DMN group expression of both TGF-β1 and, COL1-α1 mRNAs and pro-inflammatory cytokines increased, while that of 1L-10 decreased. Furthermore, LB and ALA treatments increased antioxidant activity of glutathione and decreased malondialdehyde in comparison to the DMN group. Between LB and ALA treatments, glutathione concentration was higher in the DMN + LB group, while malondialdehyde was lower. Our results indicate that both LB and ALA exert hepatoprotective effects against DMN-induced liver fibrosis. Their beneficial effects may be partly associated with down-regulation of both TGF-β1 and COL1-α1 signaling, which may be accounted for reduction of increased oxidative stress and TNF-α production.

  6. Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1α transcriptional pathway.

    Science.gov (United States)

    Jiang, Tianyi; Yin, Fei; Yao, Jia; Brinton, Roberta D; Cadenas, Enrique

    2013-12-01

    This study examines the progress of a hypometabolic state inherent in brain aging with an animal model consisting of Fischer 344 rats of young, middle, and old ages. Dynamic microPET scanning demonstrated a significant decline in brain glucose uptake at old ages, which was associated with a decrease in the expression of insulin-sensitive neuronal glucose transporters GLUT3/4 and of microvascular endothelium GLUT1. Brain aging was associated with an imbalance between the PI3K/Akt pathway of insulin signaling and c-Jun N-terminal kinase (JNK) signaling and a downregulation of the PGC1α-mediated transcriptional pathway of mitochondrial biogenesis that impinged on multiple aspects of energy homeostasis. R-(+)-lipoic acid treatment increased glucose uptake, restored the balance of Akt/JNK signaling, and enhanced mitochondrial bioenergetics and the PGC1α-driven mitochondrial biogenesis. It may be surmised that impairment of a mitochondria-cytosol-nucleus communication is underlying the progression of the age-related hypometabolic state in brain; the effects of lipoic acid are not organelle-limited, but reside on the functional and effective coordination of this communication that results in improved energy metabolism.

  7. A Regenerative Antioxidant Protocol of Vitamin E and α-Lipoic Acid Ameliorates Cardiovascular and Metabolic Changes in Fructose-Fed Rats

    Directory of Open Access Journals (Sweden)

    Jatin Patel

    2011-01-01

    Full Text Available Type 2 diabetes is a major cause of cardiovascular disease. We have determined whether the metabolic and cardiovascular changes induced by a diet high in fructose in young adult male Wistar rats could be prevented or reversed by chronic intervention with natural antioxidants. We administered a regenerative antioxidant protocol using two natural compounds: α-lipoic acid together with vitamin E (α-tocopherol alone or a tocotrienol-rich fraction, given as either a prevention or reversal protocol in the food. These rats developed glucose intolerance, hypertension, and increased collagen deposition in the heart together with an increased ventricular stiffness. Treatment with a fixed combination of vitamin E (either α-tocopherol or tocotrienol-rich fraction, 0.84 g/kg food and α-lipoic acid (1.6 g/kg food normalized glucose tolerance, blood pressure, cardiac collagen deposition, and ventricular stiffness in both prevention and reversal protocols in these fructose-fed rats. These results suggest that adequate antioxidant therapy can both prevent and reverse the metabolic and cardiovascular damage in type 2 diabetes.

  8. Use of an alpha lipoic, methylsulfonylmethane and bromelain dietary supplement (Opera(®)) for chemotherapy-induced peripheral neuropathy management, a prospective study.

    Science.gov (United States)

    Desideri, Isacco; Francolini, Giulio; Becherini, Carlotta; Terziani, Francesca; Delli Paoli, Camilla; Olmetto, Emanuela; Loi, Mauro; Perna, Marco; Meattini, Icro; Scotti, Vieri; Greto, Daniela; Bonomo, Pierluigi; Sulprizio, Susanna; Livi, Lorenzo

    2017-03-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA(®) (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA(®) supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA(®). Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA(®) was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients' population is warranted to confirm its promising activity.

  9. Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E.

    Science.gov (United States)

    Segall, A I; Moyano, M A

    2008-12-01

    The stability of ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate in topical formulations was investigated by direct reverse phase high performance liquid chromatography after sample dilution with a suitable buffer - organic solvent mixture. Ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate are derivatives of ascorbic acid which differ in hydrolipophilic properties. They are widely used in cosmetic and pharmaceutical preparations. According to the results, ascorbyl esters showed significant differences: sodium ascorbyl phosphate and magnesium ascorbyl phosphate are more stable derivatives of vitamin C than ascorbyl palmitate and may be easily used in cosmetic products.

  10. Hypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer's disease and the effect of lipoic acid: a 13C-NMR study.

    Science.gov (United States)

    Sancheti, Harsh; Patil, Ishan; Kanamori, Keiko; Díaz Brinton, Roberta; Zhang, Wei; Lin, Ai-Ling; Cadenas, Enrique

    2014-11-01

    Alzheimer's disease (AD) is characterized by age-dependent biochemical, metabolic, and physiologic changes. These age-dependent changes ultimately converge to impair cognitive functions. This study was carried out to examine the metabolic changes by probing glucose and tricarboxylic acid cycle metabolism in a 7-month-old triple transgenic mouse model of AD (3xTg-AD). The effect of lipoic acid, an insulin-mimetic agent, was also investigated to examine its ability in modulating age-dependent metabolic changes. Seven-month-old 3xTg-AD mice were given intravenous infusion of [1-(13)C]glucose followed by an ex vivo (13)C nuclear magnetic resonance to determine the concentrations of (13)C-labeled isotopomers of glutamate, glutamine, aspartate, gamma aminobutyric acid, and N-acetylaspartate. An intravenous infusion of [1-(13)C]glucose+[1,2-(13)C]acetate was given for different periods of time to distinguish neuronal and astrocytic metabolism. Enrichments of glutamate, glutamine, and aspartate were calculated after quantifying the total ((12)C+(13)C) concentrations by high-performance liquid chromatography. A hypermetabolic state was clearly evident in 7-month-old 3xTg-AD mice in contrast to the hypometabolic state reported earlier in 13-month-old mice. Hypermetabolism was evidenced by prominent increase of (13)C labeling and enrichment in the 3xTg-AD mice. Lipoic acid feeding to the hypermetabolic 3xTg-AD mice brought the metabolic parameters to the levels of nonTg mice.

  11. Estabilização do ácido lipoico via encapsulação em nanocápsulas poliméricas planejadas para aplicação cutânea Stabilization of lipoic acid by encapsulation in polymeric nanocapsules designed for cutaneous administration

    Directory of Open Access Journals (Sweden)

    Irene Clemes Külkamp

    2009-01-01

    Full Text Available This work reports the development of polymeric nanocapsules containing lipoic acid prepared by interfacial deposition of poli(ε-caprolactona. The suspensions showed acid pH and encapsulation efficiencies from 77 to 90%. Zeta potential values were from -7.42 to -5.43 mV and particle sizes were lower than 340 nm with polidispersion lower than 0.3. The stability of nanocapsules within 28 days was evaluated in terms of pH, lipoic acid content, diameter, size distribution, zeta potential and measurements of relative light backscattering. The stability of formulations containing free lipoic acid was also evaluated. Nanoencapsulation drastically improved the physico-chemical stability of lipoic acid.

  12. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells.

    Science.gov (United States)

    Salinthone, Sonemany; Schillace, Robynn V; Marracci, Gail H; Bourdette, Dennis N; Carr, Daniel W

    2008-08-13

    The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells in a dose-dependent manner. Studies using pharmacological inhibitors and receptor transfection experiments indicate that LA stimulates cAMP production via activation of the EP2 and EP4 prostanoid receptors and adenylyl cyclase. In addition, LA suppressed interleukin (IL)-12/IL-18 induced IFNgamma secretion and cytotoxicity in NK cells. These novel findings suggest that LA may inhibit NK cell function via the cAMP signaling pathway.

  13. Alpha-lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice

    Science.gov (United States)

    Abstract: Hypothermia is a key symptom of sepsis and the mechanism(s) leading to hypothermia during sepsis is largely unknown. To investigate a potential mechanism and find an effective treatment for hypothermia in sepsis, we induced hypothermia in mice by lipopolysaccharide (LP...

  14. Effect of alpha lipoic acid on the blood cell count and iron kinetics in hypertensive patients.

    Science.gov (United States)

    Mendes, Paula Renata Florêncio; Félix, Danielle dos Santos; Silva, Paulo César Dantas da; Pereira, Guêdijany Henrique; Simões, Mônica Oliveira da Silva

    2014-11-03

    Introducción: El Ácido -Lipóico (ALA) ha sido utilizado como recurso terapéutico para reducir daño oxidativo en la Hipertensión Arterial Sistémica (HAS), pero aún no existen estudios in vivo que reporten sobre su mecanismo de acción en el metabolismo del hierro. Objetivo: Evaluar el efecto antioxidante del ácido Alfa- Lipóico sobre el hemograma y metabolismo del hierro en individuos hipertensos con o sin anemia. Métodos: Estudio clínico doble-ciego, randomizado y controlado con placebo. La muestra fue constituida por 60 individuos hipertensos, distribuidos aleatoriamente en grupo tratamiento (n = 32), que recibió 600 mg/día del ALA por doce semanas y grupo control (n = 28), que recibió el placebo por el mismo período. Fueron analizados antes y después de la intervención, los parámetros del hemograma, Hierro Sérico, Ferritina, Capacidad Latente de Enlace del hierro, Capacidad Total de Enlace del Hierro, Índice de Saturación de la Transferrina (ISI) y Transferrina. Para evaluar las alteraciones entre los grupos, se utilizó el teste t de Student y el análisis de varianza ANOVA, adoptándose el nivel de significación de 5%. Resultados: Después de la intervención, el suplemento con el ALA demostró una asociación estadísticamente significativa (p < 0,05) con la reducción de los leucocitos totales, aumento del número de neutrófilos y reducciones en los niveles de Hierro Sérico e ISI. Conclusión: La administración oral del ALA como un adyuvante terapéutico, altera la respuesta hematológica del leucograma y reduce la absorción del hierro. Cabe senãlar que el mecanismo de quelación de metales por el ácido lipoico puede ser responsable de estos cambios y, en consecuencia, podría desencadenar una condicion de anemia ferropénica en individuos hipertensos.

  15. [Alpha lipoic acid and its antioxidant against cancer and diseases of central sensitization].

    Science.gov (United States)

    Durand, Marisa; Mach, Núria

    2013-01-01

    Introducción: El ácido alfa lipoico (ALA) puede controlar y limitar la cantidad de radicales libres, influyendo el desarrollo de patologías como el cáncer o las enfermedades de sensibilización central, aunque los mecanismos moleculares implicados en este proceso aún están dilucidándose. Objetivo: Reunir y contrastar información sobre las propiedades antioxidantes del ALA en la prevención y desarrollo de las patologías relacionadas con el estrés oxidativo. Material y métodos: En este trabajo, se analizan más de 100 artículos publicados en los últimos 20 años que relacionan el consumo de ALA y la prevalencia y desarrollo de patologías relacionadas con el estrés oxidativo. Los artículos han sido obtenidos en diferentes bases de datos (PubMed central, Web of Science, Elsevier Journal, Science Direct), e incluyen experimentos en células, animales y humanos. Las palabras clave utilizadas fueron: cáncer, enfermedades de sensibilización central, radicales libres, y ALA. Resultados y discusión: Se han reunido resultados de trabajos realizados in vitro y en animales de laboratorio en los que se pone de manifiesto el efecto del ALA en el control de la apoptosis celular de diferentes tipos de cánceres mediante un aumento de las especies reactivas de oxígeno, así como también el retardo en el crecimiento de las mismas. Aparte, se ha demostrado que la capacidad antioxidante del ALA y su potencial para regenerar otros antioxidantes es de gran importancia para tratar las patologías de sensibilización central. Conclusiones: El ALA ha demostrado un papel significativo como antioxidante y prooxidante en el cáncer y las patologías de sensibilización central, aunque son necesarias más investigaciones en humanos.

  16. Analysis A - cobalt Lipoic Acid and Mecobalamin, Beraprost Sodium in the Treatment of Diabetic Peripheral Neuropathy and Health Economics%a-硫辛酸、甲钴胺、贝前列腺素钠口服治疗糖尿病周围神经病变的临床及卫生经济学分析

    Institute of Scientific and Technical Information of China (English)

    王毅祯

    2015-01-01

    Objective To explore the patients with diabetic peripheral neuropathy, and observe the choice of alpha lipoic acid, beraprost sodium, and mecobalamin obtained after treatment of clinical efficacy.MethodsGather 120 cases patients with diabetic peripheral neuropathy from December 2012 to December 2014. Through the stochastic indicator method to complete all randomized patients. C1 group (alpha lipoic acid add mecobalamin group, 40 cases), C2 group (Beraprost Sodium add mecobalamin group, 40 cases), C3 group (alpha lipoic acid add Beraprost Sodium group, 40 cases), Comparison of three groups of patients for clinical curative effect and the results of the analysis of cost effectiveness, etc.Results The total effective rate in the clinical treatment, C1, C2 and C3 showed no significant difference between groups (P>0.05), In terms of cost-effectiveness analysis, C1 group is superior to the C2 and C3 group with diabetes significantly (P<0.05).Conclusion For patients with diabetic peripheral neuropathy, the clinical selection of alpha lipoic acid add a combination method of mecobalamin treatment, showed higher therapeutic effectiveness and economy, the highlight of this method in the treatment of diabetes disease.%目的探探讨针对糖尿病周围神经病变患者,观察选择α-硫辛酸、贝前列腺素钠以及甲钴胺完成治疗后获得的临床疗效。并对其卫生经济学进行认真分析。方法选取我院2012年12月~2014年12月糖尿病周围神经病变患者120例。通过随机数表法完成所有患者的随机分组。C1组(α-硫辛酸+甲钴胺组,40例);C2组(贝前列腺素钠+甲钴胺组,40例);C3组(α-硫辛酸+贝前列腺素钠组,40例);对比三组患者获得的临床疗效以及成本效果分析结果等。结果在临床治疗总有效率方面,C1组、C2组以及C3组之间,P>0.05,差异不具有统计学意义;在成本效果分析方面,C1组优于C2组以及C3组

  17. 游泳训练联合补充α-硫辛酸对WistarⅡ型糖尿病大鼠心肌线粒体的保护作用%Protective Effects of Swimming Exercise and Joint Supplement α-Lipoic Acid on Myocardial Mitochondria in Wistar Ⅱ Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    江红轲

    2012-01-01

    将60只wistar大鼠糖尿病造模完成后随机分成4组,即对照组(CON)、α-硫辛酸(LA)组、游泳训练组(SEX)和α-硫辛酸+游泳训练组(SEX+ LA)进行训练,训练结束后,检测大鼠心肌线粒体呼吸功能、氧化磷酸化蛋白表达及氧化应激相关指标,以便对游泳训练及联合补充α-硫辛酸对Ⅱ型糖尿病大鼠心肌线粒体的保护作用的内在影响机制进行探索.结果显示:α-硫辛酸和游泳运动均可以显著性改善糖尿病引起的3态呼吸水平、呼吸控制率及磷氧比值降低(P <0.05);联合作用在提高3态呼吸及降低4态呼吸方面存在增强作用(P<0.05).在对氧化磷酸化蛋白表达的影响方面,α-硫辛酸可有效提高complex Ⅰ、Ⅲ蛋白表达;游泳训练具有和α-硫辛酸相似的作用效果,且能显著性地上调complex Ⅳ表达水平(P<0.05),联合作用在提高complexⅠ、Ⅲ蛋白表达水平上存在加强作用(P <0.05).在降低组织氧化应激水平方面,各种干预方式均可降低ROS含量,提高抗氧化蛋白SOD和GSH-Px水平(P<0.05);联合作用方式在降低ROS,增强SOD水平上有叠加作用(P<0.05).以上结果说明,游泳训练及联合补充α-硫辛酸可能通过对抗氧化酶活性的提高,进一步降低ROS对呼吸链复合物及膜结构的损伤而实现线粒体呼吸功能的增强.%In the current study, after diabetic models, 60 Wistar rats randomly divided into four groups, namely the control group (CON), alpha-lipoic acid (LA) group, swimming training group (SEX) and alpha-lipoic acid + swimming training group (SEX+LA). Rats were detected myocardial mitochondrial respiratory function, oxidative phosphorylation, protein expression and oxidative stress indicators in order to elucidate swim training and joint supplement alpha-lipoic acid of type II diabetic rat heart mitochondriathe protective effect and to explore the internal influence mechanism. The results showed that alpha-lipoic acid

  18. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid Alterações na concentração de monoaminas no hipocampo de ratos produzidas pelo ácido lipóico

    OpenAIRE

    Ítala Mônica de Sales Santos; Rizângela Lyne Mendes de Freitas; Gláucio Barros Saldanha; Adriana da Rocha Tomé; Joaquín Jordán; Rivelilson Mendes de Freitas

    2010-01-01

    The purposes of the present study were to verify monoamines (dopamine (DA), norepinephrine (NE), serotonin (5-HT)), and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) contents in rat hippocampus after lipoic acid (LA) administration. Wistar rats were treated with 0.9% saline (i.p., control group) and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively). After the treatments all groups were observed f...

  19. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

    Energy Technology Data Exchange (ETDEWEB)

    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of); Won, Mooho [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2013-04-15

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC{sub 50} values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC{sub 50} = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

  20. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

    Directory of Open Access Journals (Sweden)

    Hector Garcia-Alcala

    2015-01-01

    Full Text Available Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid for 4 weeks (phase 1. Subsequently, responders were randomized to receive ALA (600 mg qd; n=16 or to ALA withdrawal (n=17 for 16 weeks (phase 2. During phase 1, the Total Symptom Score (TSS decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p<0.05 and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p<0.05. In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid administration of ALA, subsequent treatment with ALA (600 mg qd over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879.

  1. Various levels and forms of dietary α-lipoic acid in broiler chickens: Impact on blood biochemistry, stress response, liver enzymes, and antibody titers.

    Science.gov (United States)

    Kim, D W; Mushtaq, M M H; Parvin, R; Kang, H K; Kim, J H; Na, J C; Hwangbo, J; Kim, J D; Yang, C B; Park, B J; Choi, H C

    2015-02-01

    The present experiment was conducted to evaluate the impact of various levels and forms of α-lipoic acid (ALA) on blood biochemistry, immune and stress response, and antibody titers in broiler chickens. The four levels (7.5, 15, 75, and 150 ppm) and 2 sources (powder, P-ALA and encapsulated, E-ALA) of ALA along with negative (C-) and positive control (C+; contains antibiotics) diets consisted of 10 dietary treatments, and these treatments were allocated to 1,200 1-d-old chicks and were replicated 12 times with 10 birds per replicate. Among the blood biochemistry parameters, creatinine levels were almost 3 times lower in E-ALA-supplemented diets compared to the C- diet (0.09 vs. 0.25 mg/dL; P0.05). The concentration of cortisol was reduced in chickens fed ALA-supplemented diets as compared to the C- diet (Pstress in broiler chickens. The encapsulated form of ALA was more effective than the powder form.

  2. Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with α-lipoic acid.

    Directory of Open Access Journals (Sweden)

    Takayuki Koga

    Full Text Available 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA, an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; i.e., ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production.

  3. Lipoic acid inhibits the DNA repair protein O 6-methylguanine-DNA methyltransferase (MGMT) and triggers its depletion in colorectal cancer cells with concomitant autophagy induction.

    Science.gov (United States)

    Göder, Anja; Nagel, Georg; Kraus, Alexander; Dörsam, Bastian; Seiwert, Nina; Kaina, Bernd; Fahrer, Jörg

    2015-08-01

    Alkylating agents are present in food and tobacco smoke, but are also used in cancer chemotherapy, inducing the DNA lesion O (6)-methylguanine. This critical adduct is repaired by O (6)-methylguanine-DNA methyltransferase (MGMT), resulting in MGMT inactivation and degradation. In the present study, we analyzed the effects of the natural disulfide compound lipoic acid (LA) on MGMT in vitro and in colorectal cancer cells. We show that LA, but not its reduced form dihydrolipoic acid, potently inhibits the activity of recombinant MGMT by interfering with its catalytic Cys-145 residue, which was partially reversible by N-acetyl cysteine. Incubation of HCT116 colorectal cancer cells with LA altered their glutathione pool and caused a decline in MGMT activity. This was mirrored by LA-induced depletion of MGMT protein, which was not attributable to changes in MGMT messenger RNA levels. Loss of MGMT protein coincided with LA-induced autophagy, a process resulting in lysosomal degradation of proteins, including presumably MGMT. LA-stimulated autophagy in a p53-independent manner as revealed by the response of isogenic HCT116 cell lines. Knockdown of the crucial autophagy component beclin-1 and chemical inhibitors blocked LA-induced autophagy, but did not abrogate LA-triggered MGMT degradation. Concomitant with MGMT depletion, LA pretreatment resulted in enhanced O (6)-methylguanine levels in DNA. It also increased the cytotoxicity of the alkylating anticancer drug temozolomide in temozolomide-resistant colorectal cancer cells. Taken together, our study showed that the natural compound LA inhibits MGMT and induces autophagy. Furthermore, LA enhanced the cytotoxic effects of temozolomide, which makes it a candidate for a supplement in cancer therapy.

  4. Clinical Observation on Lipoic acid and Ganglioside in Treating Diabetic Neurogenic Bladder%神经节苷脂联合α-硫辛酸治疗糖尿病神经源性膀胱临床观察

    Institute of Scientific and Technical Information of China (English)

    李振兴; 谭万寿; 周斌; 金铃; 颜勇华

    2011-01-01

    Objective: The studywas designed to assess the role of lipoic acid and ganglioside in treating diabetic neurogenic bladder. Methods: Sixty patients with type 2 diabetes and diabetic neurogenic bladder were treated with lipoic acid and ganglioside for 30 days,and the postvoiding residue of bladder measured by ultrasonogram were compared before and after therapy. Results: The postvoiding residue of bladder after therapy were significantly decreased than those before therapy. Comparison of the efficacy of different programs. Results α-lipoic acid treatment control group was 90%, ganglioside treatment control group was 90%, combined treatment group was 95%, there were no significant difference between the two groups (P> 0.05), but the 3 groups Cure rates were 90.0%, 50.0%, 60.0% cure rate in treatment group than two control groups, were significantly different (P <0.05). Conclusion: Lipoic acid and ganglioside can significantly improve the postvoiding residue of bladder in patients with diabetic neurogenic bladder which Worthy to be popularized.%目的:观察α-硫辛酸、神经节苷脂联合治疗糖尿病神经源性膀胱的临床疗效.方法:60例2型糖尿病神经源性膀胱患者,随机分为α-硫辛酸治疗对照组、神经节苷脂治疗对照组,联合治疗组,疗程30d,观察症状体征及治疗前后B超膀胱残余尿量症状的变化,比较不同方案的疗效.结果:α-硫辛酸治疗对照组有效率90%,神经节苷脂治疗对照组有效率90%,联合治疗组有效率95%两组间无统计学差异(P>0.05),但3组的治愈率分别为90.0%、50.0%、60.0%,治疗组的治愈率高于两个对照组,有统计学差异(P<0.05).结论:α-硫辛酸和神经节苷脂联合治疗糖尿病神经源性膀胱有较好的临床疗效,值得临床推广.

  5. Role of α-lipoic acid in LPS/d-GalN induced fulminant hepatic failure in mice: studies on oxidative stress, inflammation and apoptosis.

    Science.gov (United States)

    Xia, Xiaomin; Su, Chuanyang; Fu, Juanli; Zhang, Pu; Jiang, Xiaoji; Xu, Demei; Hu, Lihua; Song, Erqun; Song, Yang

    2014-10-01

    This study investigated the protective effect of α-lipoic acid (LA) on lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced fulminant hepatic failure in mice. First, we found that LA markedly reduced LPS/d-GalN-induced increases in serum ALT and AST activities, which were supplemented with histopathological examination, suggested that LA has a protective effect on this model of hepatic damage. Livers challenged with LPS/d-GalN exhibited extensive areas of vacuolization with the disappearance of nuclei and the loss of hepatic architecture. On the contrary, these pathological alterations were ameliorated by LA treatment. Next, we found that ROS and TBARS levels were increased in LPS/d-GalN treated liver homogenates, which were attenuated by LA administration. Consistently, decreases in hepatic CAT and GPx activities were observed in LPS/d-GalN group and were significantly restored by LA administration. Moreover, pretreatment with LA markedly reduced LPS/d-GalN-induced iNOS, COX-2, TNF-α, NF-κB, IL-1β and IL-6 expressions. Furthermore, our data showed that TUNEL-positive cells increased in LPS/d-GalN-treated mice liver which was counteracted by LA administration. LPS/d-GalN induced apoptosis of hepatocytes, as estimated by caspase 3, caspase 8 and caspase 9 activations. Also, the increasing of Bax and the decreasing of Bcl-2 expressions also supported LPS/d-GalN induced apoptosis. Interestingly, LA marked relieved these apoptotic features. Taking together, our results indicated that LA plays an important role on LPS/d-GalN-induced fulminant hepatic failure through its antioxidant, anti-inflammatory and anti-apoptotic activities.

  6. Inhibitory effect of α-lipoic acid on thioacetamide-induced tumor promotion through suppression of inflammatory cell responses in a two-stage hepatocarcinogenesis model in rats.

    Science.gov (United States)

    Fujii, Yuta; Segawa, Risa; Kimura, Masayuki; Wang, Liyun; Ishii, Yuji; Yamamoto, Ryuichi; Morita, Reiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2013-09-25

    To investigate the protective effect of α-lipoic acid (a-LA) on the hepatocarcinogenic process promoted by thioacetamide (TAA), we used a two-stage liver carcinogenesis model in N-diethylnitrosamine (DEN)-initiated and TAA-promoted rats. We examined the modifying effect of co-administered a-LA on the liver tissue environment surrounding preneoplastic hepatocellular lesions, with particular focus on hepatic macrophages and the mechanism behind the decrease in apoptosis of cells surrounding preneoplastic hepatocellular lesions during the early stages of hepatocellular tumor promotion. TAA increased the number and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of proliferating and apoptotic cells in the liver. Co-administration with a-LA suppressed these effects. TAA also increased the numbers of ED2(+), cyclooxygenase-2(+), and heme oxygenase-1(+) hepatic macrophages as well as the number of CD3(+) lymphocytes. These effects were also suppressed by a-LA. Transcript levels of some inflammation-related genes were upregulated by TAA and downregulated by a-LA in real-time RT-PCR analysis. Outside the GST-P(+) foci, a-LA reduced the numbers of apoptotic cells, active caspase-8(+) cells and death receptor (DR)-5(+) cells. These results suggest that hepatic macrophages producing proinflammatory factors may be activated in TAA-induced tumor promotion. a-LA may suppress tumor-promoting activity by suppressing the activation of these macrophages and the subsequent inflammatory responses. Furthermore, a-LA may suppress tumor-promoting activity by suppressing the DR5-mediated extrinsic pathway of apoptosis and the subsequent regeneration of liver cells outside GST-P(+) foci.

  7. α-Lipoic Acid Treatment Improves Vision-Related Quality of Life in Patients with Dry Age-Related Macular Degeneration.

    Science.gov (United States)

    Tao, Yuan; Jiang, Pengfei; Wei, Yuhua; Wang, Ping; Sun, Xiaoling; Wang, Hong

    2016-01-01

    Dry form of age-related macular degeneration (AMD) constitutes 90% of AMD cases, and it is characterized by the formation of drusen under the retina and the slow breakdown of the light-sensing cells in the macula, which causes a gradual loss of central vision. Since oxidative stress is involved in the pathogenesis of dry AMD, α-lipoic acid (LA) with antioxidant properties was selected, and its effect on anti-oxidative markers and visual quality in patients with dry AMD was assessed. A total of 100 dry AMD patients (60-83 years old) were randomly assigned to LA treatment group (n = 50) and placebo control group (n = 50). We measured the serum superoxide dismutase (SOD) activity, an important marker of antioxidant defense, best-corrected visual acuity (BCVA), contrast sensitivity, and Chinese-Version Low Vision Quality of Life (CLVQOL) before and after LA or placebo intervention. Pearson correlation coefficients were calculated to explore the relationship between contrast sensitivity values and CLVQOL scores. There was a statistically significant increase in serum SOD activity after LA intervention. The CLVQOL score was improved significantly after LA treatment. The contrast sensitivity measured at middle and low spatial frequency was significantly higher after LA treatment. CLVQOL scores were positively correlated with contrast sensitivity at low spatial frequency (3 cyc/degree) in LA-treated group. These results indicate that LA treatment improves vision-related quality of life in patients with dry AMD probably by increasing antioxidant activity. Thus, LA can be regarded as a promising agent for the treatment of AMD.

  8. α-Lipoic Acid Inhibits Helicobacter pylori-Induced Oncogene Expression and Hyperproliferation by Suppressing the Activation of NADPH Oxidase in Gastric Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Eunyoung Byun

    2014-01-01

    Full Text Available Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori- infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as β-catenin and c-myc is related to oxidative stress. α-Lipoic acid (α-LA, a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of α-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation, levels of reactive oxygen species (ROS, NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits, activation of redox-sensitive transcription factors (NF-κB, AP-1, expression of oncogenes (β-catenin, c-myc, and nuclear localization of β-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI, an inhibitor of NADPH oxidase. As a result, α-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-κB and AP-1, induction of oncogenes, nuclear translocation of β-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-κB and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by α-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells.

  9. Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen

    Science.gov (United States)

    Di Pierro, Francesco; Settembre, Roberto

    2013-01-01

    We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day) and based on a multi-ingredient formula (Lipicur), consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects), or with carpal tunnel syndrome (45 subjects). A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur) reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome), and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain. PMID:23861596

  10. Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2013-07-01

    Full Text Available Francesco Di Pierro,1 Roberto Settembre2 1Scientific Department, Velleja Research, Milan, Italy; 2Neurosurgery Department, Di Venere Hospital, Bari, Italy Abstract: We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day and based on a multi-ingredient formula (Lipicur, consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects, or with carpal tunnel syndrome (45 subjects. A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome, and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain. Keywords: curcumin, phytosome, piperine, dexibuprofen, neuropathic pain

  11. Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model

    Institute of Scientific and Technical Information of China (English)

    Friedrich Duenschede; Ines Gockel; Alexandra K Kiemer; Theodor Junginger; Kirsten Erbes; Nina Riegler; Patrick Ewald; Achim Kircher; Stefanie Westermann; Arno Schad; Imke Miesmer; Simon Albrecht-Sch(o)ck

    2007-01-01

    AIM: To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning (IP) as well as pharmacologic pretreatment by αα-lipoic acid (LA).METHODS: Several groups of rats were compared:sham operated animals, non-pretreated animals (nt),animals receiving IP (10 min of ischemia by clamping of the portal triad and 10 min of reperfusion) prior to sustained ischemia, animals receiving selective ischemic preconditioning (IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 min of reperfusion)prior to sustained ichemia, and animals receiving 500μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia.RESULTS: Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA (19±2 vs 10±1, P<0.05 and 29±5 vs 12±1,P<0.05). Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment (3.1±0.3 vs 1.8±0.2, P<0.05). Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation (LPO) in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death.CONCLUSION: IP, consisting of 10 min of ischemia and 10 min of reperfusion, protects only partly against ischemia/reperfusion injury of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia,possibly by downregulation of pro-apoptotic Bax.

  12. Efficient synthesis of 1-azadienes derived from alpha-aminoesters. Regioselective preparation of alpha-dehydroamino acids, vinylglycines, and alpha-amino acids.

    Science.gov (United States)

    Palacios, Francisco; Vicario, Javier; Aparicio, Domitila

    2006-09-29

    An efficient synthesis of 1-azadienes derived from alpha-aminoesters is achieved through an aza-Wittig reaction of phosphazenes with beta,gamma-unsaturated alpha-ketoesters. Regioselective 1,2-reduction of these functionalized 1-azadienes affords vinylglycine derivatives, while conjugative 1,4-reduction gives alpha-dehydroamino acid compounds. Reduction of both the carbon-carbon and the imine-carbon-nitrogen double bonds leads to the formation of alpha-amino acid derivatives.

  13. Research progress in anti-oxidative and thermo-sensitive lipoic acid molecularly imprinted polymers%抗氧化温敏型硫辛酸分子印迹聚合物的研究动态

    Institute of Scientific and Technical Information of China (English)

    朱秋劲; 张进; 张孝刚; 许龙; 黄丹丹; 叶春; 陆宽

    2013-01-01

    The mutual transformation process of α-lipoic acid (ALA) and its reduction state called dihydrolipoic acid (DHLA) constitutes a good free radical scavenger in the organism. Biopolymer chitosan (CS), meanwhile, has excellent membrane-forming ability and biocompatibility. Therefore, the preparation of ALA-CS molecularly imprinted polymers (MIPs) with ALA/DHLA as template molecules and CS as functional monomer or the immobilization of MIPs on plastic films will prevent or delay the food deterioration by taking advantage of the characteristics of temperature-sensitive compounds MIPs. A review on the research progress in anti-oxidative and thermo-sensitive lipoic acid molecularly imprinted polymers was presented and the prospect of these MIPs were proposed in this paper.%α-硫辛酸(ALA)及其还原态二氢硫辛酸(DHLA)在生物体内的转化过程组成了良好的自由基清除剂,壳聚糖(CS)具有良好的成膜性能和生物相容性。以ALA/DHLA为模板分子, CS为功能单体,制备温敏型ALA-CS分子印迹聚合物(MIPs)膜或将其固载于塑料膜中,可以有效发挥温敏型化合物的特性,开发防止或延缓食品劣变的活性包装材料。本文综述了基于分子印迹膜的抗氧化型包装材料的研究进展,并对其未来发展进行了展望。

  14. [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

    Science.gov (United States)

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

  15. Alpha-Linolenic Acid: Is It Essential to Cardiovascular Health?

    NARCIS (Netherlands)

    Geleijnse, J.M.; Goede, de J.; Brouwer, I.A.

    2010-01-01

    There is a large body of scientific evidence that has been confirmed in randomized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish. For alpha-linolenic acid (ALA), which is the omega-3 fatty acid from plants, the relation to cardiovascular health is less clea

  16. Palladium-Catalyzed alpha-Arylation of Tetramic Acids

    DEFF Research Database (Denmark)

    Storgaard, Morten; Dorwald, F. Z.; Peschke, B.;

    2009-01-01

    A mild, racemization-free, palladium-Catalyzed alpha-arylation of tetramic acids (2,4-pyrrolidinediones) has been developed. Various amino acid-derived tetramic acids were cleanly arylated by treatment with 2 mol % of Pd(OAc)(2), 4 mol % of a sterically demanding biaryl phosphine, 2.3 equiv of K2CO...

  17. Iron-regulated excretion of alpha-keto acids by Salmonella typhimurium.

    OpenAIRE

    Reissbrodt, R.; Kingsley, R; Rabsch, W.; Beer, W.; Roberts, M.; Williams, P H

    1997-01-01

    Excretion of alpha-keto acids by clinical isolates and laboratory strains of Salmonella typhimurium was determined by high-performance liquid chromatography analysis of culture supernatants. The levels of excretion increased markedly with increasing iron stress imposed by the presence of alpha,alpha'-dipyridyl or conalbumin in the medium. The major product was pyruvic acid, but significant concentrations of alpha-ketoglutaric acid, alpha-ketoisovaleric acid, and alpha-ketoisocaproic acid were...

  18. Protonation and lactonization of {alpha}-iso-saccharinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Rao, L.; Tian, G. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Zhang, Z. [Washington State University, Pullman, WA 99165 (United States); Rai, D. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2005-07-01

    Full text of publication follows: {alpha}-iso-saccharinic acid, a degradation product of cellulose materials, has been a subject of study due to its ability to complex actinides and affect their migration behavior in the environment. Like other poly-hydroxy-carboxylic acids such as gluconic acid, {alpha}-iso-saccharinic acid undergoes dehydration to form {alpha}-iso-saccharinate-1,4-lactone in acidic solutions. The lactonization of iso-saccharinic acid is slower than the protonation/deprotonation reactions because it involves breaking and formation of C-O as well as O-H bonds. It is important to take into consideration the slow lactonization reaction when determining the protonation constant of iso-saccharinic acid. In this work, the protonation of a-iso-saccharinate and the lactonization of {alpha}-iso-saccharinic acid have been evaluated by potentiometry. A concept of 'composite' protonation constant, similar to the well-known composite protonation constant of carbonic acid [1], is developed for {alpha}- iso-saccharinic acid. Results on the protonation and lactonization of {alpha}-iso-saccharinic acid are discussed in comparison with gluconic acid. This research was supported by the Office of Science, Office of Basic Energy Sciences and Office of Biological and Environmental Research, U.S. Department of Energy, under Contract No. DE-AC03-76SF0098 at Lawrence Berkeley National Laboratory. [1] Stumm, W., Morgan, J.J.: 'Aquatic Chemistry: an Introduction Emphasizing Chemical Equilibria in Natural Waters', John Wiley and Sons, New York (1981), pp. 173-174. (authors)

  19. Alpha-linolenic acid protects against gentamicin induced toxicity

    Directory of Open Access Journals (Sweden)

    Priyadarshini M

    2012-11-01

    Full Text Available Medha Priyadarshini, Mohammad Aatif, Bilqees BanoDepartment of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, IndiaBackground: Recent studies indicate that reactive oxygen species are the major culprits behind the renal damage induced by gentamicin, an aminoglycoside antibiotic used to treat serious and life threatening Gram-negative infections. Experimental evidence suggests a protective role of alpha-linolenic acid supplementation against oxidative stress. The aim of the present study was to investigate the possible beneficial role of alpha-linolenic acid against gentamicin induced renal distress.Methods: Male Wistar rats were divided into three groups of eight rats each, with the first group serving as a control. The other groups were treated intraperitoneally with gentamicin 100 mg/kg body weight per day for 10 days ± alpha-linolenic acid and vitamin E (each given as 250 mg/kg body weight per day. Concentrations of creatinine, urea, cholesterol, inorganic phosphate in serum, malondialdehyde and total sulfhydryl levels, and glutathione-S-transferase, superoxide dismutase, and catalase activity in kidney tissues were determined.Results: Administration of gentamicin to rats induced marked renal failure, characterized by a profound increase in serum creatinine, urea, and cholesterol concentrations, accompanied by significant lowering of renal alkaline phosphatase and acid phosphatase activity, an increase in malondialdehyde, a decline in total sulfhydryl levels, and lowered superoxide dismutase, catalase, and glutathione-S-transferase activity. Cotreatment with alpha-linolenic acid produced amelioration in these biochemical indices of nephrotoxicity in serum as well as in tissue. Further histopathological and human studies are necessary to demonstrate the beneficial effects of alpha-linolenic acid in renal disease.Conclusion: Alpha-linolenic acid may represent a nontoxic and effective intervention strategy in

  20. Enzymatic tRNA acylation by acid and alpha-hydroxy acid analogues of amino acids.

    Science.gov (United States)

    Owczarek, Alina; Safro, Mark; Wolfson, Alexey D

    2008-01-08

    Incorporation of unnatural amino acids with unique chemical functionalities has proven to be a valuable tool for expansion of the functional repertoire and properties of proteins as well as for structure-function analysis. Incorporation of alpha-hydroxy acids (primary amino group is substituted with hydroxyl) leads to the synthesis of proteins with peptide bonds being substituted by ester bonds. Practical application of this modification is limited by the necessity to prepare corresponding acylated tRNA by chemical synthesis. We investigated the possibility of enzymatic incorporation of alpha-hydroxy acid and acid analogues (lacking amino group) of amino acids into tRNA using aminoacyl-tRNA synthetases (aaRSs). We studied direct acylation of tRNAs by alpha-hydroxy acid and acid analogues of amino acids and corresponding chemically synthesized analogues of aminoacyl-adenylates. Using adenylate analogues we were able to enzymatically acylate tRNA with amino acid analogues which were otherwise completely inactive in direct aminoacylation reaction, thus bypassing the natural mechanisms ensuring the selectivity of tRNA aminoacylation. Our results are the first demonstration that the use of synthetic aminoacyl-adenylates as substrates in tRNA aminoacylation reaction may provide a way for incorporation of unnatural amino acids into tRNA, and consequently into proteins.

  1. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-l-carnitine and/or R-α-lipoic acid

    Science.gov (United States)

    Liu, Jiankang; Head, Elizabeth; Gharib, Afshin M.; Yuan, Wenjun; Ingersoll, Russell T.; Hagen, Tory M.; Cotman, Carl W.; Ames, Bruce N.

    2002-01-01

    Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-l-carnitine (ALCAR) [0.5% or 0.2% (wt/vol) in drinking water], and/or R-α-lipoic acid (LA) [0.2% or 0.1% (wt/wt) in diet]. Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and/or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2′-deoxyguanosine) increased with age in the hippocampus, a region important for memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALCAR and/or LA significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that ALCAR and/or LA reversed age-associated mitochondrial structural decay. These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function. PMID:11854529

  2. UK Food Standards Agency alpha-linolenic acid workshop report

    NARCIS (Netherlands)

    Sanderson, P; Finnegan, YE; Williams, CM; Calder, PC; Burdge, GC; Wootton, SA; Griffin, BA; Millward, DJ; Pegge, NC; Bemelmans, WJE

    2002-01-01

    The UK Food Standards Agency convened a group of expert scientists to review current research investigating whether n-3 polyunsaturated fatty acids (PUFA) from plant oils (alpha-linolenic acid; ALA) were as beneficial to cardiovascular health as the n-3 PUFA from the marine oils, eicosapentaenoic ac

  3. Studies of iso-alpha-acids : analysis, purification, and stability.

    NARCIS (Netherlands)

    Khatib, Alfi

    2006-01-01

    The female cones of hop (Humulus lupulus L.) are added to beer, providing taste and flavour and contributing to the stability of foam. The main constituents of hop related to these properties are generically known as alpha-acids. During the brewing process, these acids are isomerized, resulting in t

  4. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maëlle Lempereur

    2016-01-01

    Full Text Available Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L. which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box. In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells. Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.

  5. Regulation of Vascular Tone, Angiogenesis and Cellular Bioenergetics by the 3-Mercaptopyruvate Sulfurtransferase/H2S Pathway: Functional Impairment by Hyperglycemia and Restoration by DL-α-Lipoic Acid.

    Science.gov (United States)

    Coletta, Ciro; Módis, Katalin; Szczesny, Bartosz; Brunyánszki, Attila; Oláh, Gábor; Rios, Ester C S; Yanagi, Kazunori; Ahmad, Akbar; Papapetropoulos, Andreas; Szabo, Csaba

    2015-02-18

    Hydrogen sulfide (H2S), as a reducing agent and an antioxidant molecule, exerts protective effects against hyperglycemic stress in the vascular endothelium. The mitochondrial enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is an important biological source of H2S. We have recently demonstrated that 3-MST activity is inhibited by oxidative stress in vitro and speculated that this may have an adverse effect on cellular homeostasis. In the current study, given the importance of H2S as a vasorelaxant, angiogenesis stimulator and cellular bioenergetic mediator, we first determined whether the 3-MST/H2S system plays a physiological regulatory role in endothelial cells. Next, we tested whether a dysfunction of this pathway develops during the development of hyperglycemia and μmol/L to diabetes-associated vascular complications. Intraperitoneal (IP) 3-MP (1 mg/kg) raised plasma H2S levels in rats. 3-MP (10 1 mmol/L) promoted angiogenesis in vitro in bEnd3 microvascular endothelial cells and in vivo in a Matrigel assay in mice (0.3-1 mg/kg). In vitro studies with bEnd3 cell homogenates demonstrated that the 3-MP-induced increases in H2S production depended on enzymatic activity, although at higher concentrations (1-3 mmol/L) there was also evidence for an additional nonenzymatic H2S production by 3-MP. In vivo, 3-MP facilitated wound healing in rats, induced the relaxation of dermal microvessels and increased mitochondrial bioenergetic function. In vitro hyperglycemia or in vivo streptozotocin diabetes impaired angiogenesis, attenuated mitochondrial function and delayed wound healing; all of these responses were associated with an impairment of the proangiogenic and bioenergetic effects of 3-MP. The antioxidants DL-α-lipoic acid (LA) in vivo, or dihydrolipoic acid (DHLA) in vitro restored the ability of 3-MP to stimulate angiogenesis, cellular bioenergetics and wound healing in hyperglycemia and diabetes. We conclude that diabetes leads to an impairment of the 3-MST

  6. HPLC Analysis of [Alpha]- and [Beta]-Acids in Hops

    Science.gov (United States)

    Danenhower, Travis M.; Force, Leyna J.; Petersen, Kenneth J.; Betts, Thomas A.; Baker, Gary A.

    2008-01-01

    Hops have been used for centuries to impart aroma and bitterness to beer. The cones of the female hop plant contain both essential oils, which include many of the fragrant components of hops, and a collection of compounds known as [alpha]- and [beta]-acids that are the precursors to bittering agents. In order for brewers to predict the ultimate…

  7. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

    Science.gov (United States)

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-09-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  8. Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

    Energy Technology Data Exchange (ETDEWEB)

    Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.; Thorn, Katherine J.; Christianson, David W. (MIT); (Episcopal U); (Rutgers); (Drexel); (Penn)

    2011-10-21

    Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.

  9. Clinical Observation of Alprostadil Combined with Lipoic Acid in the Treat-ment of Diabetic Peripheral Neuropathy%前列地尔联合硫辛酸治疗糖尿病周围神经病变的临床探讨

    Institute of Scientific and Technical Information of China (English)

    车微娟

    2015-01-01

    目的:探讨前列地尔联合硫辛酸治疗糖尿病周围神经病变的疗效。方法选择该院就诊的糖尿病周围神经病变患者62例,随机分为两组。其中对照组30例采用前列地尔治疗;观察组32例采用前列地尔联合硫辛酸治疗。结果治疗2周后,观察组神经传导速度及临床效果均优于对照组,差异有统计学意义(P<0.05)。结论前列地尔联合硫辛酸应用可改善糖尿病周围神经病变神经传导阻滞。%Objective To investigate the curative effect of alprostadil combined with lipoic acid in treatment of diabetic pe-ripheral neuropathy. Methods 62 patients with diabetic peripheral neuropathy were randomly divided into 2 groups. The control group of 30 cases treated by alprostadil; observation group of 32 cases, treated by alprostadil combined with lipoic acid. Results After 2 weeks of treatment, the nerve conduction velocity and clinical effect of the observation group were bet-ter than those of the control group, the difference was statistically significant (P<0.05). Conclusion Alprostadil combined with lipoic acid can improve nerve conduction block lesions of diabetic peripheral nerve.

  10. 硫辛酸对早期糖尿病足患者氧化应激与炎症反应的影响%The Effect of Lipoic Acid on Oxidative Stress and Inflammatory Reaction in Patients With Early Diabetic Foot

    Institute of Scientific and Technical Information of China (English)

    任艳莉; 李可心

    2016-01-01

    Objective To understand the effect of lipoic acid on oxidative stress and inflammatory reaction in patients with early diabetic foot. Methods90 patients with early diabetic foot were randomly divided into experimental group and control group, patients in control group were treated with conventional therapy, patients in the experimental group were treated with conventional hypoglycemic therapy plus the treatment of lipoic acid,the oxidative stress and inlfammatory reaction in the two groups were compared.Results The oxidative stress and inlfammatory reaction in the experimental group were lighter than the control group. Conclusion The oxidative stress and inlfammatory reaction in diabetic foot patients can be reduced by lipoic acid.%目的:研究硫辛酸对早期糖尿病足患者氧化应激与炎症反应的影响。方法将90例早期糖尿病足患者随机分为实验组和对照组,对照组使用常规降糖治疗,实验组在常规降糖治疗的基础上加硫辛酸的治疗方式,比较两组患者的氧化应激和炎症反应。结果实验组的氧化应激及炎症反应都要轻于对照组。结论硫辛酸能够减轻糖尿病足患者的氧化应激状态和炎症反应。

  11. Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

    Directory of Open Access Journals (Sweden)

    Hiroshi Honda

    2016-01-01

    Full Text Available The alpha-linolenic acid (ALA-diacylglycerol (DAG oil is an edible oil enriched with DAG (>80% and ALA (>50%. Although DAG oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of DAG. Therefore, the purpose of this study was to evaluate the genotoxicity of ALA-DAG oil using standard genotoxicity tests in accordance with the OECD guidelines. ALA-DAG oil showed negative results in the bacterial reverse mutation test (Ames test and in vitro micronucleus test in cultured Chinese hamster lung cells with and without metabolic activation, and in the in vivo bone marrow micronucleus test in mice. Our results did not show any genotoxicity, suggesting that the fatty acid composition had no deleterious effects. We conclude that ALA-DAG oil had no genotoxicity concerns under the testing conditions.

  12. 钙蛋白酶抑制剂、α-硫辛酸单用及联用治疗癌性恶病质%Caplain inhibitor and α-lipoic acid used alone or in combination for cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    陈思曾; 曹少祥

    2013-01-01

    目的 探讨钙蛋白酶(caplain)抑制剂ALLN(N-acetyl-Leu-Leu-Norleucinal)、α-硫辛酸(α-LA)单用及联用对癌性恶病质小鼠的治疗效果及其机制.方法 结肠腺癌Colon26 (C26)细胞接种于小鼠前腋窝皮下构建恶病质模型.药物干预7d后检测去瘤体质量、腓肠肌湿重、血生化、细胞因子水平、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、肿瘤组织核因子-κB(NF-κB)表达及骨骼肌中caplain-1和泛素mRNA表达.结果 荷瘤对照组caplain-1与泛素mRNA表达值分别为0.84 ±0.10、2.68±0.08,ALLN组、α-LA组、ALLN+ α-LA组caplain-1表达值分别为0.59 ±0.07、0.65±0.07、0.57 ±0.04,泛素mRNA表达值分别为2.29±0.07、2.34 ±0.05、2.20±0.10,均低于荷瘤对照组(P<0.05),其他指标亦有不同程度的改善(P<0.05).结论 caplain抑制剂和α-硫辛酸均具改善癌症恶病质的作用,两者联合应用效果更好.%Objective To study the treatment effects by using calpain inhibitor N-acetyl-Leu-LeuNorleucinal (ALLN) and α-lipoic acid (α-LA) alone or in combination for mice with cancer cachexia and the possible mechanism.Methods Murine colon 26 adenocarcinoma cells were inoculated subcutaneously into the anterior subaxilla of Balb/c mice to establish cachexia modcl.Tumor-free body weight and wet weight of gastrocnemius were measured,and the levels of serum biochemistry parameters,cytokines,malondialdehyde (MAD),superoxide dismutase (SOD),nuclear factor-κB (NF-κB),caplain-1 and ubiquitin mRNA in skeletal muscle were detected at 7th day after intervention.Results The absorbance (A)ratio of calpain-1 and ubiquitin mRNA in tumor-bearing control group was 0.84 ± 0.10 and 2.68 ± 0.08,that of calpain-1 in ALLN group,α-LA group and ALLN + α-LA group was 0.59 ± 0.07,0.65 ± 0.07 and 0.57 ± 0.04,and that of ubiquitin mRNA in ALLN group,α-LA group and ALLN + α-LA group was 2.29 ± 0.07,2.34 ± 0.05 and 2.20 ± 0.10,respectively.The A ratio of calpain-I and

  13. Effect of α-lipoic acid on cognitive function after cardiopulmonary bypass in diabetic rats%α-硫辛酸对糖尿病大鼠体外循环后认知功能的影响

    Institute of Scientific and Technical Information of China (English)

    尹光明; 姚尚龙; 舒化青

    2012-01-01

    Objective To evaluate the effect of α-lipoic acid on the cognitive function after cardiopulmonary bypass (CPB) in diabetic rats.Methods Health adult male Sprague-Dawley rats,weighing 400-500 g,aged 16-22 weeks,were used in this study.Diabetes mellitus was induced by intraperitoneal streptozocin 60 mg/kg and confirmed by blood glucose≥ 16.7 mmol/L.Thirty-two diabetic rats were randomly divided into 2 groups (n =16 each):diabetes mellitus group (group D) and α-lipoi cacid group (group L).In group L,α-lipoic acid 30 mg/kg was intraperitoneally injected once a day for 7 consecutive days starting from 6th week after induction of diabetes mellitus.While the equal volume of normal saline was given instead in group D.The two groups underwent CPB after the last administration.Before induction of diabetes mellitus,on 5th week after induction of diabetes mellitus,before CPB,at the end of CPB,and on 3 and 5 days after termination of CPB,10 rats were chosen from each group and venous blood samples were collected for determination of plasma TNF-α and IL-10 concentrations.Ten rats in each group were chosen for detection of cognitive function before induction of diabetes mellitus,before CPB and 5 days after termination of CPB.The rats were then sacrificed and hippocampi were isolated for measurement of NF-κB activity.Results Compare with group D,the plasma TNF-α concentration,times of electric shock and activity of NF-κB in hippocampal tissues were significantly decreased and the plasma IL-10 concentration was increased in group L (P < 0.05 or 0.01).Conclusion α-lipoic acid can improve the cognitive function after CPB in diabetic rats and inhibition of activation of NF-κB in hippocampal neurons is involved in the mechanism.%目的 评价α-硫辛酸对糖尿病大鼠体外循环(CPB)后认知功能的影响.方法 成年雄性SD大鼠,体重400~ 450 g,16 ~ 22周龄,腹腔注射1%链脲佐菌素60 mg/kg建立糖尿病模型.取糖尿

  14. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid Alterações na concentração de monoaminas no hipocampo de ratos produzidas pelo ácido lipóico

    Directory of Open Access Journals (Sweden)

    Ítala Mônica de Sales Santos

    2010-06-01

    Full Text Available The purposes of the present study were to verify monoamines (dopamine (DA, norepinephrine (NE, serotonin (5-HT, and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC, homovanillic acid (HVA and 5-hydroxyindoleacetic acid (5-HIAA contents in rat hippocampus after lipoic acid (LA administration. Wistar rats were treated with 0.9% saline (i.p., control group and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively. After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.O objetivo do presente estudo foi verificar a concentração das monoaminas (dopamina (DA, norepinefrina (NA, serotonina (5-HT, e seus metabólitos (ácido 3,4-hidroxifenil (DOPAC, ácido homovanílico (HVA e 5 ácido hydroxiindolacético (5-HIAA no hipocampo de ratos após administração do ácido lipóico (AL. Ratos Wistar foram tratados com solução salina 0,9% (i.p., grupo controle e AL (10, 20 ou 30 mg/kg, i.p., AL10, AL20 e AL30 grupos, respectivamente. Após os tratamentos todos os grupos foram observados durante 24 h. O conteúdo de DA no hipocampo de ratos foi aumentado apenas com AL na dose de 20 mg/kg dose. A concentração de serotonina e do seu metabólito 5-HIAA também foi diminuída com esta dose de AL. Por outro lado, os níveis de DOPAC e de HVA não mostrram nenhuma mudança significativa. As alterações na concentração das monoaminas hipocampais podem ser sugeridas como um possível mecanismo de ação cerebral deste antioxidante. O resultado do estudo pode

  15. Protective Effects of Lipoic Acid on Myocardial Injury in SIRS Rats Induced by Lipopolysaccharide%硫辛酸对内毒素诱导的 SIRS大鼠心肌损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    范志文; 汤彦

    2015-01-01

    ABSTRACT:Objective To explore the protective effects of different dose of lipoic acid onmyocardial inju-ry rats with systemic inflammatory response syndrome ( SIRS) induced by lipopolysaccharide .Methods A total of 75 healthy SD rats were enrolled .Among them,60 rats were intraperitoneally injected with 25mg/kg LPS to establish SIRS model of myocardial injury ,thenthose rats were divided into negative control group ,LA high-dose group ,LA middle-dose group and LA low-dose group ,15 rats in each group .the other 15 rats were intraperitone-ally injected with saline solution ( normal group ) .The levels of NF-κB and IL-1 in myocardium were detected with real-time PCR after 24h,48h and 72h,respectively,and the level of TNF-αwas measured with ELISA.HE staining was used to observe the microscopical change of myocradium tissue .Results After challenge with LPS , the levels of NF-κB,IL-1 and TNF-αin myocardium in negative control group were the highest at 72h.Com-pared with the negative control group ,the levels of NF-κB,IL-1 and TNF-αin LA high-dose group and LA mid-dle-dose group were decreased after treatment for 24h,48h and 72h(P<0.05).With LA dose increase,myo-cardial tissue inflammation reduced accordingly .Conclusion Lipoic acid has a protective effect on myocardial injury of SIRS rats,and the underlyingmechnism may be correlated with inhibition of NF-κB activation and the down-regulation of IL-1 and TNF-αexpression .%目的:以内毒素( lipopolysaccharide ,LPS)诱导法建立全身炎症反应综合征( SIRS)大鼠心肌损伤模型,探讨不同浓度硫辛酸( lipoic acid,LA)对大鼠心肌损伤的保护作用。方法选择健康SD大鼠75只,其中60只腹腔注射内毒素25mg/kg,构建SIRS大鼠心肌损伤模型,再分为阴性对照组、LA大剂量组、LA中剂量组、LA小剂量组,每组15只;其余15只大鼠为正常组。分别于24、48、72h后采用real-time PCR检测各组每只大鼠心

  16. Manoyl oxide alpha-arabinopyranoside and grindelic acid diterpenoids from Grindelia integrifolia.

    Science.gov (United States)

    Ahmed, A A; Mahmoud, A A; Ahmed, U M; El-Bassuony, A A; Abd El-Razk, M H; Pare, P W; Karchesy, J

    2001-10-01

    Two new manoyl oxide-alpha-arabinopyranoside diterpenoids, 15-hydroxy-13-epi-manoyl oxide-14-O-alpha-L-arabinopyranoside (tarapacol-14-O-alpha-L-arabinopyranoside) (1) and 15-acetoxy-13-epi-manoyl oxide-14-O-alpha-L-arabinopyranoside (tarapacol-15-acetate-14-O-alpha-L-arabinopyranoside) (2), as well as a new grindelic acid derivative, 19-hydroxygrindelic acid (3), together with five known diterpenoids (tarapacol, tarapacanol A, grindelic acid, methyl grindeloate, 3beta-hydroxygrindelic acid, 4) were isolated from the aerial parts of Grindelia integrifolia. The structures of 1-3 were elucidated by spectral data analysis.

  17. Impact of Omega-3 Supplementation with Alpha-Linolenic Acid on Neuronal Cell Fatty Acid Status

    OpenAIRE

    Densel, Owen

    2016-01-01

    A method of treating retinoic acid differentiated SH-SY5Y neuroblastoma cells with alpha-linolenic acid (ALA) in the free acid form has been developed in order to examine impacts of such supplementation on fatty acid composition of cells and on functional outcomes. Through Bovine Serum Albumin: ALA conjugation, an ALA treatment media was created and compared to the stock media which contained no detectible amounts of ALA. Results from fatty acid analysis of the control cells (n=3) and ALA-sup...

  18. PGC-1alpha inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Oleic acid (OA stimulates vascular smooth muscle cell (VSMC proliferation and migration. The precise mechanism is still unclear. We sought to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARgamma coactivator-1 alpha (PGC-1alpha on OA-induced VSMC proliferation and migration. PRINCIPAL FINDINGS: Oleate and palmitate, the most abundant monounsaturated fatty acid and saturated fatty acid in plasma, respectively, differently affect the mRNA and protein levels of PGC-1alpha in VSMCs. OA treatment resulted in a reduction of PGC-1alpha expression, which may be responsible for the increase in VSMC proliferation and migration caused by this fatty acid. In fact, overexpression of PGC-1alpha prevented OA-induced VSMC proliferation and migration while suppression of PGC-1alpha by siRNA enhanced the effects of OA. In contrast, palmitic acid (PA treatment led to opposite effects. This saturated fatty acid induced PGC-1alpha expression and prevented OA-induced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1alpha on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation. CONCLUSIONS: OA and PA regulate PGC-1alpha expression in VSMCs differentially. OA stimulates VSMC proliferation and migration via suppression of PGC-1alpha expression while PA reverses the effects of OA by inducing PGC-1alpha expression. Upregulation of PGC-1alpha in VSMCs provides a potential novel strategy in preventing atherosclerosis.

  19. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress and nitrate tolerance.

    Science.gov (United States)

    Wenzel, Philip; Hink, Ulrich; Oelze, Matthias; Schuppan, Swaantje; Schaeuble, Karin; Schildknecht, Stefan; Ho, Kwok K; Weiner, Henry; Bachschmid, Markus; Münzel, Thomas; Daiber, Andreas

    2007-01-05

    Chronic therapy with nitroglycerin results in a rapid development of nitrate tolerance, which is associated with an increased production of reactive oxygen species. We have recently shown that mitochondria are an important source of nitroglycerin-induced oxidants and that the nitroglycerin-bioactivating mitochondrial aldehyde dehydrogenase is oxidatively inactivated in the setting of tolerance. Here we investigated the effect of various oxidants on aldehyde dehydrogenase activity and its restoration by dihydrolipoic acid. In vivo tolerance in Wistar rats was induced by infusion of nitroglycerin (6.6 microg/kg/min, 4 days). Vascular reactivity was measured by isometric tension studies of isolated aortic rings in response to nitroglycerin. Chronic nitroglycerin infusion lead to impaired vascular responses to nitroglycerin and decreased dehydrogenase activity, which was corrected by dihydrolipoic acid co-incubation. Superoxide, peroxynitrite, and nitroglycerin itself were highly efficient in inhibiting mitochondrial and yeast aldehyde dehydrogenase activity, which was restored by dithiol compounds such as dihydrolipoic acid and dithiothreitol. Hydrogen peroxide and nitric oxide were rather insensitive inhibitors. Our observations indicate that mitochondrial oxidative stress (especially superoxide and peroxynitrite) in response to organic nitrate treatment may inactivate aldehyde dehydrogenase thereby leading to nitrate tolerance. Glutathionylation obviously amplifies oxidative inactivation of the enzyme providing another regulatory pathway. Furthermore, the present data demonstrate that the mitochondrial dithiol compound dihydrolipoic acid restores mitochondrial aldehyde dehydrogenase activity via reduction of a disulfide at the active site and thereby improves nitrate tolerance.

  20. alpha-Linolenic acid protects renal cells against palmitic acid lipotoxicity via inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Katsoulieris, Elias; Mabley, Jon G; Samai, Mohamed; Green, Irene C; Chatterjee, Prabal K

    2009-11-25

    Unsaturated fatty acids may counteract the lipotoxicity associated with saturated fatty acids. Palmitic acid induced endoplasmic reticulum (ER) stress and caused apoptotic and necrotic cell death in the renal proximal tubular cell line, NRK-52E. We investigated whether alpha-linolenic acid, an unsaturated fatty acid, protected against ER stress and cell death induced by palmitic acid or by other non-nutrient ER stress generators. Incubation of NRK-52E cells for 24h with palmitic acid produced a significant increase in apoptosis and necrosis. Palmitic acid also increased levels of three indicators of ER stress - the phosphorylated form of the eukaryotic initiation factor 2alpha (eIF2alpha), C/EBP homologous protein (CHOP), and glucose regulated protein 78 (GRP78). alpha-Linolenic acid dramatically reduced cell death and levels of all three indicators of ER stress brought about by palmitic acid. Tunicamycin, which induces ER stress by glycosylation of proteins, produced similar effects to those obtained using palmitic acid; its effects were partially reversed by alpha-linolenic acid. Salubrinal (a phosphatase inhibitor) causes increased levels of the phosphorylated form of eIF2alpha - this effect was partially reversed by alpha-linolenic acid. Palmitoleate, a monosaturated fatty acid, had similar effects to those of alpha-linolenic acid. These results suggest that part of the mechanism of protection of the kidney by unsaturated fatty acids is through inhibition of ER stress, eIF2alpha phosphorylation and consequential reduction of CHOP protein expression and apoptotic renal cell death.

  1. Transport and metabolic effects of alpha-aminoisobutyric acid in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kim, K W; Roon, R J

    1982-11-24

    alpha-Aminoisobutyric acid is actively transported into yeast cells by the general amino acid transport system. The system exhibits a Km for alpha-aminoisobutyric acid of 270 microM, a Vmax of 24 nmol/min per mg cells (dry weight), and a pH optimum of 4.1-4.3. alpha-Aminoisobutyric acid is also transported by a minor system(s) with a Vmax of 1.7 nmol/min per mg cells. Transport occurs against a concentration gradient with the concentration ratio reaching over 1000:1 (in/out). The alpha-aminoisobutyric acid is not significantly metabolized or incorporated into protein after an 18 h incubation. alpha-Aminoisobutyric acid inhibits cell growth when a poor nitrogen source such as proline is provided but not with good nitrogen sources such as NH+4. During nitrogen starvation alpha-aminoisobutyric acid strongly inhibits the synthesis of the nitrogen catabolite repression sensitive enzyme, asparaginase II. Studies with a mutant yeast strain (GDH-CR) suggest that alpha-aminoisobutyric acid inhibition of asparaginase II synthesis occurs because alpha-aminoisobutyric acid is an effective inhibitor of protein synthesis in nitrogen starved cells.

  2. Photolysis of hop-derived trans-iso-alpha-acids and trans-tetrahydroiso-alpha-acids: product identification in relation to the lightstruck flavour of beer.

    Science.gov (United States)

    Heyerick, Arne; Zhao, Yining; Sandra, Pat; Huvaere, Kevin; Roelens, Frederik; De Keukeleire, Denis

    2003-03-01

    The photolysis of hop-derived trans-iso-alpha-acids (2a-c; naturally occurring bitter compounds present in beer) and of trans-tetrahydroiso-alpha-acids (5a-c; semi-synthetic advanced hop products) was investigated at 300 nm in methanol. The complex photoreaction mixtures were separated by high-performance liquid chromatography (HPLC) using diode array detection and the major photoreaction products were identified by HPLC-mass spectroscopy. The main part of the mixture consisted of compounds, which originated from recombination of radicals derived from Norrish Type I photocleavage of the acyloin moiety in both trans-iso-alpha-acids and trans-tetrahydroiso-alpha-acids. The results confirm the intermediacy of radicals that were previously identified by time-resolved electron paramagnetic resonance and they bear relevance to the formation of the lightstruck flavour that is generated when beer is exposed to light. Additionally, new photoproducts were found that are formed by photochemical reactions hitherto undiscovered in hop chemistry, including photoenolization of trans-isohumulone (2a) leading to trans-alloisohumulone (13a) and a retro oxa-di-pi-methane rearrangement in trans-isohumulone (2a) and trans-tetrahydroiso-alpha-acids to humulone (1a) and tetrahydro-alpha-acids (23a-b), respectively.

  3. Foam-stabilizing effects and cling formation patterns of iso-alpha-acids and reduced iso-alpha-acids in lager beer.

    Science.gov (United States)

    Kunimune, Takeshi; Shellhammer, Thomas H

    2008-09-24

    Foam-stabilizing properties and cling formation patterns of iso-alpha-acids and reduced iso-alpha-acids were investigated using an unhopped lager beer. Unhopped beer was dosed with iso-alpha-acid (Iso), rho-iso-alpha-acid (Rho), tetrahydro-iso-alpha-acid (Tetra), and hexahydro-iso-alpha-acid (Hexa), separately, over a range of concentrations from 2 to 10 ppm. A uniform foam was created by Inpack 2000 Flasher Head and was measured by a NIBEM Foam Stability Tester (NIBEM-TPH) followed by a NIBEM Cling Meter (NIBEM-CLM) to determine the relationship between the concentration and NIBEM-30 and the cling formation ability of each compound. The foam-stabilizing power was determined to be Tetra, Hexa, Iso, and Rho from the strongest to weakest. Linear regression models were created using the NIBEM-TPH data set, and on the basis of 95% confidence intervals, the foam stability of Tetra or Hexa became significantly larger than that of Iso when 2.4 or 4.2 ppm of Tetra or Hexa was used as a replacement for Iso, respectively. Cling formation patterns could be categorized into three groups: "ring", "mesh", and "powdery". The control beer had the lowest foam stability and did not yield any foam cling.

  4. Clinical observation on Lipoic Acid and Pyridostigmine Bromide in treating diabetic neurogenic bladder%α-硫辛酸、溴吡斯的明联合治疗糖尿病神经源性膀胱疗效观察

    Institute of Scientific and Technical Information of China (English)

    曹萌; 王涛; 陈雪辉

    2011-01-01

    Objective: To observe the efficacy of Lipoic Acid and Pyridostigmine Bromide in treating diabetic neurogenic bladder.Methods: 40 patients with type 2 diabetes and diabetic neurogenic bladder were treated with Lipoic Acid and Pyridostigmine Bromide for two weeks, and the postvoiding residue of bladder measured by ultragonogram were compared before and after therapy.Results: The postvoiding residue of bladder after therapy (40±8) ml were significantly decreased than those before therapy (205±l 1) ml (t=6.677, P<0.001).The postvoiding residue of bladder four weeks after drug discontinuance (20±5) ml were significantly decreased than those before therapy (205±ll) ml (t=7.033, P<0.001).Conclusion: Lipoic Acid and Pyridostigmine Bromide can significantly improve the postvoiding residue of bladder in patients with diabetic neurogenic bladder.%目的:观察α-硫辛酸、溴吡斯的明联合治疗糖尿病神经源性膀胱的临床疗效.方法:40例2型糖尿病神经源性膀胱患者,给予α-硫辛酸、溴吡斯的明联合治疗2周,比较治疗前后B超膀胱残余尿量的变化.结果:治疗后B超测定的膀胱残余尿量(40±8)ml较治疗前(205±11)ml有明显减少(t=6.677,P<0.001);停药4周后B超测定的膀胱残余尿量(20±5)ml,较治疗前(205±11)ml有明显减少(t=7.033,P<0.001).结论:α-硫辛酸、溴吡斯的明联合治疗糖尿病神经源性膀胱,可以明显改善尿潴留,有较好的临床疗效.

  5. α-硫辛酸联合甲钴胺治疗化疗药引起周围神经病变的疗效观察%Efficacy of α-Lipoic Acid combined with Mecobalamin for Chemotherapy-induced Peripheral Neuropathy

    Institute of Scientific and Technical Information of China (English)

    郑志高; 陈毅德; 洪东花; 林雨标; 郑文慧

    2015-01-01

    目的:观察硫辛酸联合甲钴胺治疗化疗药所致周围神经病变的疗效。方法:将126例恶性肿瘤化疗后周围神经病变患者随机分为治疗组和对照组,每组63例。治疗组给予α-硫辛酸600 mg静脉滴注、1日1次,甲钴胺500μg,静脉注射、1日1次;对照组单用甲钴胺500μg,静脉注射、1日1次,疗程均为2周。比较2组患者治疗前后临床疗效。结果:治疗组患者总有效率为80.95%(51/63),对照组为47.62%(30/63),治疗组优于对照组,差异有统计学意义(P<0.05)。结论:α-硫辛酸联合甲钴胺治疗化疗药引起周围神经病变安全、有效。%OBJECTIVE:To evaluate the clinical efficacy of α-lipoic acid plus mecobalamin for peripheral neuropathy induced by chemotherapy.METHODS:One hundred and tweenty six patients with chemotherapy-induced peripheral neuropathy were randomly divided into two groups ( of 63 cases each) to be treated with eitherα-lipoic acid (600 mg) q.d by intravenous infusion plus mecobalamin (500 μg) q.d by intravenous injection ( treatment groups) or with mecobalamin (500μg) q.d by intravenous infusion ( control group) for 2 weeks, the clinical efficacy between the two groups were compared.RESULTS: The response rate in the treatment group was better than in the control gorup [ 80.95%( 51/63 ) vs.47.62%( 30/63 ) , P <0.05 ] . CONCLUSIONS: α-Lipoic acid combined with mecobalamin are safe and effective in the treatment of peripheral neuropathy induced by chemotherapy.

  6. Therapeutic effect of α-lipoic acid combined with mecobalamin and alprostadil on diabetic peripheral neuropathy%α-硫辛酸联合甲钴胺及前列地尔治疗糖尿病周围神经病变的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张菁; 邓晓龙; 王敏哲

    2011-01-01

    目的 评价α-硫辛酸联合甲钴胺及前列地尔治疗糖尿病周围神经病变(DPN)的疗效.方法 将32例患者随机分为两组:治疗组予α-硫辛酸、甲钴胺及前列地尔,对照组予甲钴胺及前列地尔,治疗2周.观察两组临床疗效及神经传导速度(NCV).结果 治疗组总有效率达87.5%,明显高于对照组的50%(P<0.05);两组患者的神经病变主觉症状问卷(TSS)评分明显改善(P<0.05);治疗组NCV较对照组有显著提高(P< 0.01).结论 临床使用α-硫辛酸联合甲钴胺及前列地尔治疗DPN安全有效.%Objective To evaluate the therapeutic effect of α-lipoic acid combined with mecobalamin and alprostadil on diabetic peripheral neuropathy(DPN). Methods The 32 DPN patients receiving a 2 weeks of therapy were randomly divided into two groups: treatment group treated with α-lipoic acid combined with mecobalamin and alprostadil and control group treated with mecobalamin and alprostadil.The therapeutic effect and nerve conduction velocity(NCV)were observed. Results The total efficacious rate was higher in treatment group than in control group (87. 5% vs 50. 0%, P<0. 05). TSS score improvement in treatment group was superior to control group (P<0. 05). NCV acceleration was more in treatment group than in control (P<0.01). Conclusions Treatment with α-lipoic acid combined with mecobalamin and alprostadil in patients with DPN is safe and effective.

  7. Clinical observation of α-lipoic acid and shuxuening combined with mecobalamin in treatment of diabetic peripheral neuropathy%α-硫辛酸、舒血宁联合甲钴胺治疗糖尿病周围神经病变的临床观察

    Institute of Scientific and Technical Information of China (English)

    潘宁; 李旭东; 吕燕

    2014-01-01

    目的:观察α-硫辛酸、舒血宁联合甲钴胺治疗糖尿病周围神经病变( DPN)的临床疗效。方法将70例DPN患者随机分为两组,观察组采用α-硫辛酸+舒血宁+甲钴胺治疗,对照组采用甲钴胺治疗。观察两组的临床疗效、神经传导速度、多伦多临床评分系统( TCSS)的评分与血浆超敏C-反应蛋白( hs-CRP)水平在治疗前后的变化。结果观察组总有效率为91.43%,高于对照组的71.43%,差异有统计学意义( P﹤0.05);治疗后两组TCSS评分、血浆hs-CRP水平均明显降低,神经传导速度( NCV)均增加,上述指标改善情况观察组优于对照组,差异有统计学意义( P﹤0.05)。结论α-硫辛酸、舒血宁联合甲钴胺治疗糖尿病周围神经病变疗效确切。%Objective To observe the clinical efficacy ofα-lipoic acid and shuxuening combined with mecobalamin on diabetic peripheral neuropathy( DPN). Methods Seventy patients with DPN were randomly divided into two groups( observation group and control group),observation group was given α-lipoic acid,shuxuening and mecobalamin,control group was given mecobalamin. The clinical efficacy, the improving condition of NCV,the TCSS score and the peripheral blood level of hs-CRP before and af-ter treatment was observed. Results The efficacy of observation group(91. 43%)was higher than that of control group(71. 43%),there was significant difference(P﹤0. 05). The TCSS score,the levels of hs-CRP were significantly reduced( P ﹤0. 05 ),and the NCV obviously increased( P ﹤0. 05 )in both group after treatment,and there were significant differences between the two groups after treatment( P﹤0. 05). Conclusions α-lipoic acid,shuxuening combining with mecobalamin is effective on diabetic peripheral neuropathy.

  8. A specific acid [alpha]-glucosidase in lamellar bodies of the human lung

    OpenAIRE

    Vries, A.C.J. de; Schram, A.W.; Tager, J.M.; Batenburg, J.J.

    2006-01-01

    In the present investigation, we have demonstrated that three lysosomal-type hydrolases, alpha-glucosidase, alpha-mannosidase and a phosphatase, are present in lamellar bodies isolated from adult human lung. The hydrolase activities that were studied, all showed an acidic pH optimum, which is characteristic for lysosomal enzymes. The properties of acid alpha-glucosidase in the lamellar body fraction and that in the lysosome-enriched fraction were compared. Using specific antibodies against ly...

  9. α-硫辛酸联合甲钴胺治疗2型糖尿病患者糖尿病周围神经病变的疗效观察%Effects of α-lipoic acid in combination with mecobalamin on diabetic peripheral neuropathy in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    黄晓敏; 刘伟芳

    2014-01-01

    目的 观察α-硫辛酸联合甲钴胺治疗2型糖尿病患者糖尿病周围神经病变(DPN)的疗效.方法 符合入选条件的DPN患者68例,随机分为观察组与对照组,每组各34例.观察组给予α-硫辛酸600 mg/d静脉滴注及甲钴胺500μg/d静脉滴注,对照组给予甲钴胺500μg/d静脉滴注,共治疗3周.在治疗前、治疗后分别进行神经病变主觉症状问卷(TSS)评分及神经传导速度测定并观察有无药物不良反应.结果 组内比较:与治疗前相比,两组患者治疗后TSS评分均有下降(P<0.01),神经传导速度均有加快(P<0.01);组间比较:治疗后观察组患者TSS评分下降比对照组显著,两组比较差异有统计学意义(P<0.05),治疗后两组患者神经传导速度比较差异无统计学意义(P>0.05).两组均未见严重药物不良反应.结论 α-硫辛酸与甲钴胺联合治疗能有效且安全地治疗2型糖尿病患者DPN,联合治疗对DPN阳性症状的改善作用优于甲钴胺单药治疗.%Objective To observe the efficacy of α-lipoic acid in combination with mecobalamin for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus.Methods 68 patients with DPN were randomly divided into observation group and control group with each group of 34 cases.The observation group received α-lipoic acid 600 mg/d and mecobalamin 500 μ g/d by intravenous drip for 3 weeks,and the control group received mecobalamin 500 μ g/d by intravenous drip for 3 weeks.Before treatment and after treatment,their total symptoms score (TSS) and nerve conductive velocity were measured and compared,and the side effects of drugs were observed.Results Compared with that before treatment,the TSS was decreased and nerve conductive velocity was accelerated significantly after 3 weeks of treatment in both groups (all P < 0.01).Compared with the control group,the TSS decrease of the observation group was more obvious after treatment and the difference was significant

  10. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  11. THE ANTIOXIDATIVE EFFECT OF α-LIPOIC ACID ON BLOOD CELL MITOCHONDRIA OF AGED RATS%α-硫辛酸对老年大鼠外周血细胞线粒体的抗氧化作用

    Institute of Scientific and Technical Information of China (English)

    田芳; 赵鹏; 袁准; 孙宇立; 邵春海; 刘景芳

    2012-01-01

    目的 探讨α-硫辛酸(α-LA)对老年大鼠线粒体活性氧及膜电位的影响.方法 以18月龄老年大鼠为研究对象,6月龄大鼠作为青年对照.不同浓度硫辛酸灌胃饲养7d、停止灌胃3d、再次恢复灌胃7d,用双氢罗丹明123 (DHR123)标记外周血细胞线粒体活性氧,罗丹明123 (Rh123)指示线粒体膜电位,借助流式细胞仪评价LA对老龄大鼠体内细胞活性氧及膜电位的改变.结果 老年大鼠外周血细胞线粒体活性氧水平高于青年对照,线粒体膜电位低于青年对照.LA灌胃饲养7d后,实验组老年大鼠活性氧水平低于老年对照组(P<0.05),线粒体膜电位高于老年对照组(P<0.05).停止灌胃3d后,各实验组活性氧水平不同程度回升,高剂量组较明显;各实验组线粒体膜电位变化不明显.继续用LA灌胃7d,各实验组活性氧水平不同程度下降,线粒体膜电位变化无统计意义.结论 LA能清除活性氧,稳定线粒体膜电位;LA对活性氧的抑制有浓度依赖性,对线粒体膜电位的稳定作用较持久.%Objective To investigate the antioxidantive effect of a-lipoic acid (a-LA) on the mitochondria of elderly Sprague Dawley (SD) rats. Method Sprague Dawley rats of 18 mo old were fed diet with a-LA as the experiment group. The control group was fed with the same diet without LA . The experiment group was fed LA diet for 1 w, then ceased feeding for 3 d, and continued feeding for another week. In the last day of each stage, Rhodaminel23 (Rhl23) was used as fluorescent probe to indicate mitochondrial membrane potential. Dihydrorho- daminel23 (DHR123) was used to indicate mitochondrial ROS. Fluorescent signal was detected and analyzed by flow cytometry. Results Mitochondrial ROS level was higher and membrane potential was lower in the experiment groups than the control group. The ROS level was increased in the LA feeding stage and dropped after ceasing. The mitochondrial membrane potential was increased in the first

  12. Effect of alpha-linolenic, capric and lauric acid on the fatty acid biosynthesis in Staphylococcus aureus.

    Science.gov (United States)

    Sado-Kamdem, Sylvain L; Vannini, Lucia; Guerzoni, M Elisabetta

    2009-02-28

    The antimicrobial activity of alpha-linolenic, capric and lauric acids on Staphylococcus aureus was studied in relation to their effect on the de novo fatty acid biosynthesis. Labelled acetate was used as integrated carbon source and traced in the de novo fatty acid by using a GC-Mass spectrometer and the single ion monitoring (SIM) technique. The detection of the incorporation of the labelled carbon into the individual cell fatty acids (FAs) provided an insight into the different effects of alpha-linolenic, capric and lauric acids on the FA biosynthesis. The results suggested that FAs pathway is the major target of alpha-linolenic acid and that other enzymes in addition to FabI are involved in S. aureus response mechanism when medium chain fatty acids are present.

  13. PGC-1alpha activates CYP7A1 and bile acid biosynthesis.

    Science.gov (United States)

    Shin, Dong-Ju; Campos, Jose A; Gil, Gregorio; Osborne, Timothy F

    2003-12-12

    Cholesterol 7-alpha-hydroxylase (CYP7A1) is the key enzyme that commits cholesterol to the neutral bile acid biosynthesis pathway and is highly regulated. In the current studies, we have uncovered a role for the transcriptional co-activator PGC-1alpha in CYP7A1 gene transcription. PGC-1alpha plays a vital role in adaptive thermogenesis in brown adipose tissue and stimulates genes important to mitochondrial function and oxidative metabolism. It is also involved in the activation of hepatic gluconeogenesic gene expression during fasting. Because the mRNA for CYP7A1 was also induced in mouse liver by fasting, we reasoned that PGC-1alpha might be an important co-activator for CYP7A1. Here we show that PGC-1alpha and CYP7A1 are also co-induced in livers of mice in response to streptozotocin induced diabetes. Additionally, infection of cultured HepG2 cells with a recombinant adenovirus expressing PGC-1alpha directly activates CYP7A1 gene expression and increases bile acid biosynthesis as well. Furthermore, we show that PGC-1alpha activates the CYP7A1 promoter directly in transient transfection assays in cultured cells. Thus, PGC-1alpha is a key activator of CYP7A1 and bile acid biosynthesis and is likely responsible for the fasting and diabetes dependent induction of CYP7A1. PGC-1alpha has already been shown to be a critical activator of several other oxidative processes including adaptive thermogenesis and fatty acid oxidation. Our studies provide further evidence of the fundamental role played by PGC-1alpha in oxidative metabolism and define PGC-1alpha as a link between diabetes and bile acid metabolism.

  14. Uptake of neutral alpha- and beta-amino acids by human proximal tubular cells

    DEFF Research Database (Denmark)

    Jessen, H; Røigaard, H; Jacobsen, Christian

    1996-01-01

    The transport characteristics of amino acids in primary cell cultures from the proximal tubule of human adults (AHKE cells) were examined, using alpha-aminoisobutyric acid (AIB) and beta-alanine as representatives of alpha- and beta-amino acids, respectively. The Na(+)-gradient dependent influx...... of AIB occurred by a single, saturable transport system, whereas the Na(+)-gradient dependent uptake data for beta-alanine could be described in terms of two-independent transport components as well as one-transport one-leak model with identical kinetic constants for the high-affinity system. Competition...... experiments revealed that all the neutral amino acids tested reduced the uptake of AIB, whereas there was no effect of taurine, L-aspartic acid, and L-arginine. By contrast, the influx of beta-alanine was only drastically reduced by beta-amino acids, whereas the inhibition by neutral alpha-amino acids...

  15. Amino acids allosterically regulate the thiamine diphosphate-dependent alpha-keto acid decarboxylase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Werther, Tobias; Spinka, Michael; Tittmann, Kai; Schütz, Anja; Golbik, Ralph; Mrestani-Klaus, Carmen; Hübner, Gerhard; König, Stephan

    2008-02-29

    The gene rv0853c from Mycobacterium tuberculosis strain H37Rv codes for a thiamine diphosphate-dependent alpha-keto acid decarboxylase (MtKDC), an enzyme involved in the amino acid degradation via the Ehrlich pathway. Steady state kinetic experiments were performed to determine the substrate specificity of MtKDC. The mycobacterial enzyme was found to convert a broad spectrum of branched-chain and aromatic alpha-keto acids. Stopped-flow kinetics showed that MtKDC is allosterically activated by alpha-keto acids. Even more, we demonstrate that also amino acids are potent activators of this thiamine diphosphate-dependent enzyme. Thus, metabolic flow through the Ehrlich pathway can be directly regulated at the decarboxylation step. The influence of amino acids on MtKDC catalysis was investigated, and implications for other thiamine diphosphate-dependent enzymes are discussed.

  16. A specific acid [alpha]-glucosidase in lamellar bodies of the human lung

    NARCIS (Netherlands)

    Vries, A.C.J. de; Schram, A.W.; Tager, J.M.; Batenburg, J.J.

    2006-01-01

    In the present investigation, we have demonstrated that three lysosomal-type hydrolases, alpha-glucosidase, alpha-mannosidase and a phosphatase, are present in lamellar bodies isolated from adult human lung. The hydrolase activities that were studied, all showed an acidic pH optimum, which is charac

  17. Importance of tetrahydroiso alpha-acids to the microbiological stability of beer.

    Science.gov (United States)

    Caballero, Isabel; Agut, Montserrat; Armentia, Alicia; Blanco, Carlos A

    2009-01-01

    While beer provides a very stable microbiological environment, a few niche microorganisms are capable of growth in malt, wort, and beer. The production of off-flavors and development of turbidity in the packaged product are due to the growth and metabolic activity of wild yeast, certain lactic acid bacteria (LAB) and anaerobic Gram-negative bacteria. Beer also contains bitter hop compounds, which are toxic to Gram-positive and Gram-negative bacteria, and contribute to preventing the spoilage of this beverage. In the boiling process, the hop alpha-acids (humulones) are isomerized into iso alpha-acids. These products are responsible for the bitter taste of beer, but they also play an essential role in enhancing foam stability. Antibacterial activity of iso alpha-acids and their hydrogenated derivates (rhoiso alpha-acids and tetrahydroiso alpha-acids) in MRS broth and beer have been evaluated against different LAB (Lactobacillus and Pediococcus) for the determination of their beer-stabilizing capabilities. Besides this, we have determined the minimum inhibitory concentration and the bacteriostatic effect of each compound against Pediococcus. We found that tetrahydroiso alpha-acids (added directly to beer during production processes) are the compounds that present the greatest antibacterial activity against the main agents implicated in beer spoilage.

  18. Phytanic acid alpha-oxidase deficiency (Refsum disease) presenting in infancy.

    Science.gov (United States)

    Herbert, M A; Clayton, P T

    1994-01-01

    This report describes a patient with high serum phytanic acid concentration due to phytanic acid alpha-oxidase deficiency (classical Refsum disease). He presented unusually early, hypotonia and developmental delay being apparent by 7 months. A generalized peroxisomal disorder (so-called 'infantile Refsum disease') was excluded by analyses of pristanic acid, very long-chain fatty acids, bile acids and plasmalogen synthesis. The early presentation raises the possibility of in utero exposure to phytanate.

  19. Nucleic acid (cDNA) and amino acid sequences of alpha-type gliadins from wheat (Triticum aestivum).

    OpenAIRE

    Kasarda, D.D.; Okita, T W; Bernardin, J. E.; Baecker, P A; Nimmo, C C; Lew, E J; Dietler, M D; Greene, F C

    1984-01-01

    The complete amino acid sequence for an alpha-type gliadin protein of wheat (Triticum aestivum Linnaeus) endosperm has been derived from a cloned cDNA sequence. An additional cDNA clone that corresponds to about 75% of a similar alpha-type gliadin has been sequenced and shows some important differences. About 97% of the composite sequence of A-gliadin (an alpha-type gliadin fraction) has also been obtained by direct amino acid sequencing. This sequence shows a high degree of similarity with a...

  20. Differential modulation of alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors expressed in Xenopus oocytes by flufenamic acid and niflumic acid.

    Science.gov (United States)

    Zwart, R; Oortgiesen, M; Vijverberg, H P

    1995-03-01

    Effects of flufenamic acid (FFA) and niflumic acid (NFA), which are often used to block Ca(2+)-activated Cl- current, have been investigated in voltage-clamped Xenopus oocytes expressing alpha 3 beta 2 and alpha 3 beta 4 nicotinic ACh receptors (nAChRs). NFA and FFA inhibit alpha 3 beta 2 nAChR-mediated inward currents and potentiate alpha 3 beta 4 nAChR-mediated inward currents in normal, Cl(-)-free and Ca(2+)-free solutions to a similar extent. The concentration-dependence of the inhibition of alpha 3 beta 2 nAChR-mediated ion current yields IC50 values of 90 microM for FFA and of 260 microM for NFA. The potentiation of alpha 3 beta 4 nAChR-mediated ion current by NFA yields an EC50 value of 30 microM, whereas the effect of FFA does not saturate for concentrations of up to 1 mM. At 100 microM, FFA reduces the maximum of the concentration-effect curve of ACh for alpha 3 beta 2 nAChRs, but leaves the EC50 of ACh unaffected. The same concentration of FFA potentiates alpha 3 beta 4 nAChR-mediated ion currents for all ACh concentrations and causes a small shift of the concentration-effect curve of ACh to lower agonist concentrations. The potentiation, like the inhibition, is most likely due to a noncompetitive effect of FFA. Increasing ACh-induced inward current either by raising the agonist concentration from 10 microM to 200 microM or by coapplication of 10 microM ACh and 200 microM FFA causes a similar enhancement of block of the alpha 3 beta 4 nAChR-mediated ion current by Mg2+. This suggests that the effects of FFA and of an increased agonist concentration result in a similar functional modification of the alpha 3 beta 4 nAChR-operated ion channel. It is concluded that alpha 3 beta 4 and alpha 3 beta 2 nAChRs are oppositely modulated by FFA and NFA through a direct beta-subunit-dependent effect.

  1. Stable right- and left-handed peptide helices containing C(alpha)-tetrasubstituted alpha-amino acids.

    Science.gov (United States)

    Grauer, Andreas A; Cabrele, Chiara; Zabel, Manfred; König, Burkhard

    2009-05-15

    Short peptidomimetics with stable secondary structures in solution are of interest for applications in chemistry, biology, and medicine. One way to rigidify the backbone of a peptide is the use of cyclic C(alpha)-tetrasubstituted alpha-amino acids (TAAs) like compound 14. The structures resulting from the incorporation of this unnatural amino acid into peptides were investigated. In total, 13 different peptides with a length of up to eight residues and alternating sequences of TAA 14 and (S)- or (R)-valine were synthesized. Their structures were characterized by X-ray diffraction analysis and NMR and CD measurements showing that the all-S-backbone-configured peptides 5 and 6 (SS)(2-3) form right-handed 3(10)-helices, while the all-R-configured peptides 11-13 (RR)(2-4) form left-handed 3(10)-helices in the solid state and solution.

  2. Appearance and cellular distribution of lectin-like receptors for alpha 1-acid glycoprotein in the developing rat testis

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    glycoprotein glycoforms to their receptors is inhibited by steroids. Testosterone, oestradiol and progesterone inhibited the binding of alpha 1-acid glycoprotein glycoform A to its receptor. Cortisone, aldosterone, oestradiol and progesterone inhibited the binding of alpha 1-acid glycoprotein glycoforms B......A histochemical avidin-biotin technique with three different alpha 1-acid glycoprotein glycoforms showed pronounced alterations in the cellular localization of two alpha 1-acid glycoprotein lectin-like receptors during cell differentiation in the developing rat testis. The binding of alpha 1-acid...... and C to their receptor. A difference in the cellular content of alpha 1-acid glycoprotein glycoforms and alpha 1-acid glycoprotein receptors separates the spermatocytes and the early spermatids from the late spermatids. The difference in receptor composition implies a difference in the effect...

  3. Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1999-01-01

    Using a histochemical technique with three different alpha 1-acid glycoprotein glycoform one glycoform specific receptor has been identified in human adrenal cortex. The receptor is associated to alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C. The glycoform specific...... specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution....... The binding activity was dependent on the presence of calcium ions and not on thiol reagents. Thus the lectin-like receptor may belong to the C-type lectin family. Using an antibody to alpha 1-acid glycoprotein the presence of alpha 1-acid glycoprotein was observed in the same location as the glycoform...

  4. Nucleic acid (cDNA) and amino acid sequences of alpha-type gliadins from wheat (Triticum aestivum).

    Science.gov (United States)

    Kasarda, D D; Okita, T W; Bernardin, J E; Baecker, P A; Nimmo, C C; Lew, E J; Dietler, M D; Greene, F C

    1984-01-01

    The complete amino acid sequence for an alpha-type gliadin protein of wheat (Triticum aestivum Linnaeus) endosperm has been derived from a cloned cDNA sequence. An additional cDNA clone that corresponds to about 75% of a similar alpha-type gliadin has been sequenced and shows some important differences. About 97% of the composite sequence of A-gliadin (an alpha-type gliadin fraction) has also been obtained by direct amino acid sequencing. This sequence shows a high degree of similarity with amino acid sequences derived from both cDNA clones and is virtually identical to one of them. On the basis of sequence information, after loss of the signal sequence, the mature alpha-type gliadins may be divided into five different domains, two of which may have evolved from an ancestral gliadin gene, whereas the remaining three contain repeating sequences that may have developed independently. Images PMID:6589619

  5. Adsorption of gaseous formaldehyde and carboxylic acids by ammonium-ion-exchanged alpha-zirconium phosphate.

    Science.gov (United States)

    Hayashi, A; Fujimoto, Y; Ogawa, Y; Nakayama, H; Tsuhako, M

    2005-03-01

    Ammonium-ion-exchanged alpha-Zr(HPO(4))(2)H(2)O (alpha-ZrP) was obtained as a single phase with the interlayer distance of 9.4 A by the ion-exchange of proton with ammonium ion. The ammonium ion-exchanged alpha-ZrP could adsorb ill-smelling gases, such as formaldehyde and carboxylic acids (formic acid, acetic acid, propionic acid, and butyric acid). The adsorption amounts of carboxylic acids increased in the order, butyric acidacidacidacid, whereas the adsorption amount of formaldehyde was the same as that of butyric acid. It was cleared that the adsorbed formaldehyde was partially decomposed to formic acid and methanol by self oxidation-reduction reaction in the interlayer region as evidenced by solid-state NMR. Thereby the interlayer distance after the adsorption of formaldehyde expanded to 14.4 A. In the case of formic acid, it was cointercalated into the interlayer region, and the interlayer distance expanded to 11.1 A. On the other hand, the interlayer distance of the other carboxylic acid-adsorbed compounds decreased to 7.6 A due to release by the evacuation.

  6. Natively unfolded human prothymosin alpha adopts partially folded collapsed conformation at acidic pH.

    Science.gov (United States)

    Uversky, V N; Gillespie, J R; Millett, I S; Khodyakova, A V; Vasiliev, A M; Chernovskaya, T V; Vasilenko, R N; Kozlovskaya, G D; Dolgikh, D A; Fink, A L; Doniach, S; Abramov, V M

    1999-11-09

    Prothymosin alpha has previously been shown to be unfolded at neutral pH, thus belonging to a growing family of "natively unfolded" proteins. The structural properties and conformational stability of recombinant human prothymosin alpha were characterized at neutral and acidic pH by gel filtration, SAXS, circular dichroism, ANS fluorescence, (1)H NMR, and resistance to urea-induced unfolding. Interestingly, prothymosin alpha underwent a cooperative transition from the unfolded state into a partially folded conformation on lowering the pH. This conformation of prothymosin alpha is a compact denatured state, with structural properties different from those of the molten globule. The formation of alpha-helical structure by the glutamic acid-rich elements of the protein accompanied by the partial hydrophobic collapse is expected at lower pH due to the neutralization of the negatively charged residues. It is possible that such conformational changes may be associated with the protein function.

  7. Response of Substituted Indoleacetic Acids in the Indolo-alpha-pyrone Fluorescence Determination

    DEFF Research Database (Denmark)

    Engvild, Kjeld Christensen; Böttger, M.; Kaiser, P.

    1978-01-01

    .-pyrones. Other halogenated indoleacetic acids show between zero and 60% of the fluorescence of IAA. Apparently the concentration of IAA cannot be determined in crude extracts in the presence of 4-chloro- or 5-hydroxy-indoleacetic acid, because separate determinations of each of these compounds are not possible......The method of indolo-.alpha.-pyrone fluorescence-determination of IAA was investigated to study possible interference from 4-chloro-indoleacetic acid and 5-hydroxyindoleacetic acid, which occur naturally. Both compounds show about 40% of the fluorescence of IAA after conversion into their .alpha...

  8. Anti-apoptosis effect of lipoic acid-niacin diad on acrolein-induced apoptosis in ARPE-19 cells%硫辛酸烟酸二联体拮抗丙烯醛诱导ARPE-19细胞凋亡的作用机制

    Institute of Scientific and Technical Information of China (English)

    邹秀兰; 王观峰; 李文立; 皮荣标; 俞永珍; 邹玉平

    2014-01-01

    Objective To investigate the regulations of Bax , Bcl-2 in the protection of lipoic acid-niacin diad in acrolein-induced apoptosis in ARPE-19 cells. Methods The ARPE-19 cells were cultured in medium containing 10% fetal bovine serum , at 37 ℃ with 5% CO2. The ARPE-19 was transferred to 6-well plate after reaching to 70% confluence. After starvation for 24 h , the cells in 6-well plates were divided into three groups , including the blank control group , the acrolein treatment group with 50 μmol/L acrolein for 24 h , and the protection group with 100 μmol/L lipoic acid-niacin diad for 24 h and with the acrolein for another 24 h. The apoptotic cells were detected by flow cytometry assay , and expressions of Bcl-2 , Bax protein were detected by Western Blot assay. Results The percentages of normal healthy cells were 94.8%, 60.98%, and 91.34% in the blank control group , 50 μmol/L acrolein group and 100 μmol/L diad contained of lipoic acid and niacin group , respectively. The ratios of Bax/Bcl-2 protein expression were 0.293 9, 1.389 2, and 0.555 8 in the blank control group, 50 μmol/L acrolein group and 100 μmol/L diad contained of lipoic acid and niacin group, respectively. Conclusion The protective effect of lipoic acid-niacin diad on acrolein-induced apoptosis in ARPE-19 cell through promoting Bcl-2 expression and inhibiting Bax expression.%目的:探讨Bax、Bcl-2蛋白在硫辛酸烟酸二联体拮抗丙烯醛诱导的体外培养 ARPE-19细胞凋亡中可能的调控作用。方法:ARPE-19细胞置于含有10%体积分数胎牛血清的DMEM培养基,37℃、体积分数5%CO2培养箱中培养,待培养瓶底部ARPE-19细胞长至70%时,种6孔板,用不含血清的DMEM培养基培养24 h ,细胞换液。实验分为3组:空白对照组、丙烯醛组和硫辛酸烟酸二联体组。细胞流式检测各组ARPE-19细胞凋亡情况,Western blot检测Bax、Bcl-2蛋白的表达水平。结果:细胞流式显示正常细

  9. Recent developments in the catalytic asymmetric synthesis of alpha- and beta-amino acids.

    Science.gov (United States)

    Ma, Jun-An

    2003-09-22

    The stereoselective synthesis of amino acids is of great importance for the construction of optically active natural products and pharmaceuticals. Apart from enzymes, a broad repertoire of chiral reagents, auxiliaries, and catalysts can be used for the formation of amino acids. Asymmetric reactions using catalytic amounts of chiral molecules provide efficient methods for the generation of optically active proteinogenic and nonproteinogenic amino acids. This minireview collects recent work on catalytic asymmetric synthesis of alpha- and beta-amino acids.

  10. Separation of basic drug enantiomers by capillary electrophoresis using chicken alpha1-acid glycoprotein: insight into chiral recognition mechanism.

    Science.gov (United States)

    Matsunaga, Hisami; Sadakane, Yutaka; Haginaka, Jun

    2003-08-01

    Recombinant chicken alpha(1)-acid glycoprotein (alpha(1)-AGP) was prepared by the Escherichia coli expression system and completely deglycosylated alpha(1)-AGP (cd-alpha(1)-AGP) was obtained by treatments of native alpha(1)-AGP with a mixture of endoglycosidase and N-glycosidase. The average molecular masses of chicken alpha(1)-AGP, cd-alpha(1)-AGP and recombinant alpha(1)-AGP were estimated to be about 29 200, 21 700 and 20 700, respectively, by matrix-assisted laser desorption-time of flight-mass spectrometry. We compared the chiral recognition ability of chicken alpha(1)-AGP, cd-alpha(1)-AGP and recombinant alpha(1)-AGP using them as chiral selectors in capillary electrophoresis. The chicken alpha(1)-AGP showed higher resolution for eperisone, pindolol and tolperisone than cd-alpha(1)-AGP or recombinant alpha(1)-AGP. Recombinant alpha(1)-AGP still showed chiral recognition for three basic drugs tested. By addition of propranolol as a competitor in the separation solution in CE, no enantioseparations of three basic drugs were observed with chicken alpha(1)-AGP, cd-alpha(1)-AGP or recombinant alpha(1)-AGP. These results reveal that the protein domain of the chicken alpha(1)-AGP is responsible for the chiral recognition ability, and that the chiral recognition site(s) for basic drugs exists on the protein domain.

  11. Synthesis and evaluation of novel [alpha]-heteroaryl-phenylpropanoic acid derivatives as PPAR[alpha/gamma] dual agonists

    Energy Technology Data Exchange (ETDEWEB)

    Casimiro-Garcia, Agustin; Bigge, Christopher F.; Davis, Jo Ann; Padalino, Teresa; Pulaski, James; Ohren, Jeffrey F.; McConnell, Patrick; Kane, Christopher D.; Royer, Lori J.; Stevens, Kimberly A.; Auerbach, Bruce; Collard, Wendy; McGregor, Christine; Song, Kun; Pfizer

    2010-09-27

    The synthesis of a new series of phenylpropanoic acid derivatives incorporating an heteroaryl group at the {alpha}-position and their evaluation for binding and activation of PPAR{alpha} and PPAR{gamma} are presented in this report. Among the new compounds, (S)-3-{l_brace}4-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-phenyl{r_brace}-2-1,2,3-triazol-2-yl-propionic acid (17j), was identified as a potent human PPAR{alpha}/{gamma} dual agonist (EC{sub 50} = 0.013 and 0.061 {micro}M, respectively) with demonstrated oral bioavailability in rat and dog. 17j was shown to decrease insulin levels, plasma glucose, and triglycerides in the ZDF female rat model. In the human apolipoprotein A-1/CETP transgenic mouse model 17j produced increases in hApoA1 and HDL-C and decreases in plasma triglycerides. The increased potency for binding and activation of both PPAR subtypes observed with 17j when compared to previous analogs in this series was explained based on results derived from crystallographic and modeling studies.

  12. Synthesis of alpha-hydroxyphosphonic acids from Lesquerella oil

    Science.gov (United States)

    Lesquerella oil has been a substance of growing chemical interest, due to the ease with which it is produced and its similarity in structure to castor oil. The primary fatty acid in Lesquerella oil, lesquerolic acid, is very similar to the principal component of castor oil, ricinoleic acid, and may ...

  13. Synthesis of Long Chain Unsaturated-alpha,omega-Dicarboxylic Acids from Renewable Materials via Olefin Metathesis

    Science.gov (United States)

    The self-metathesis reaction of soy, rapeseed, tall, and linseed oil fatty acids was investigated for the synthesis of symmetrical long-chain unsaturated-alpha,omega-dicarboxylic acids. The metathesis reactions were carried out in the presence of a Grubbs catalyst under solvent-free conditions at a...

  14. Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

    Energy Technology Data Exchange (ETDEWEB)

    Jessen, Holly Jean; Liao, Hans H; Gort, Steven John; Selifonova, Olga V

    2014-11-18

    The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

  15. Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

    Energy Technology Data Exchange (ETDEWEB)

    Jessen, Holly Jean [Chanhassen, MN; Liao, Hans H [Eden Prairie, MN; Gort, Steven John [Apple Valley, MN; Selifonova, Olga V [Plymouth, MN

    2011-10-04

    The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

  16. Effects of Lipoic Acid on Abnormal Distortion Product Otoacoustic Emissions Without Hearing Lose Following Blast Noise Exposure%硫辛酸对纯音听力损失前畸变产物耳声发射异常的作用及意义

    Institute of Scientific and Technical Information of China (English)

    何端军; 郭万宏; 唐建勇; 张家超; 杨静芬; 付艳秋

    2013-01-01

    Objective To investigate the effect of lipoic acid on abnormally low distortion product otoacoustic emissions (DPOAE) with no hearing loss following military noise exposure. Methods Twenty six (41ears) artillerymen,with normal pure tone hearing thresholds and abnormal DPOAEs amplitudes following military noise exposure were randomly divided into 2 groups. The test group with 13 young adults (21 ears) received intravenous drip of lipoic acid (600 mg/day). The control group with 13 young adults (20 ears) received intravenous drip of placebo. Pure tone audiomety and otoacoustic emission were per-formed on Days 2, 4, 6, 8 and 10 after treatment. Pure tone hearing thresholds and amplitudes of DPOAEs were compared and analyzed. Results Statistical analysis showed that prior to the treatment the amplitudes of DPOAE at 3, 4 , 6 and 8 kHz did not differ significantly between the two groups. DPOAE amplitudes in the control group increased significantly on the 8th day after treatment. The amplitudes in the test group increased significantly on the 4th day after treatment, with a significant differ-ence between the test and control groups. Conclusion Lipoic acid seems to significantly improve DPOAE amplitudes toward normal in individuals with subclinical auditory system impairment caused by military noise exposure.%目的观察脉冲噪声致纯音听力损失前畸变产物耳声发射(DPOAE)异常的自然转归及硫辛酸对其转归的影响。方法纯音听阈正常、DPOAE异常者26例(41耳),随机分为对照组和治疗组,每组各13例。治疗组给予硫辛酸600mg/日静滴治疗,对照组给予安慰剂治疗,治疗后第2、4、6、8、10天,分别进行纯音听阈及DPOAE检查。结果治疗前两组各对应频率的纯音听阈及DPOAE幅值均无显著差别,DPOAE异常频率主要发生在3、4、6、8kHz。经过治疗后,两组的纯音听阈无明显变化,对照组异常频率的DPOAE的幅值自第8天开始,显著大

  17. Kinetic studies of acid inactivation of alpha-amylase from Aspergillus oryzae

    DEFF Research Database (Denmark)

    Carlsen, Morten; Nielsen, Jens Bredal; Villadsen, John

    1996-01-01

    The stability of alpha-amylase from Aspergillus oryzae has been studied at different pH. The enzyme is extremely stable at neutral pH (pH 5-8), whereas outside this pH-range a substantial loss of activity is observed. The acid-inactivation of alpha-amylase from A. oryzae was monitored on-line by ......The stability of alpha-amylase from Aspergillus oryzae has been studied at different pH. The enzyme is extremely stable at neutral pH (pH 5-8), whereas outside this pH-range a substantial loss of activity is observed. The acid-inactivation of alpha-amylase from A. oryzae was monitored on...

  18. Involvement of vacuolar sequestration and active transport in tolerance of Saccharomyces cerevisiae to hop iso-alpha-acids.

    Science.gov (United States)

    Hazelwood, Lucie A; Walsh, Michael C; Pronk, Jack T; Daran, Jean-Marc

    2010-01-01

    The hop plant, Humulus lupulus L., has an exceptionally high content of secondary metabolites, the hop alpha-acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso-alpha-acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso-alpha-acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso-alpha-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the S. cerevisiae haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-alpha-acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-alpha-acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso-alpha-acids and alteration of cell wall structure and, to a lesser extent, active export of iso-alpha-acids across the plasma membrane. Furthermore, iso-alpha-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.

  19. An NMR and ab initio quantum chemical study of acid-base equilibria for conformationally constrained acidic alpha-amino acids in aqueous solution

    DEFF Research Database (Denmark)

    Nielsen, Peter Aadal; Jaroszewski, Jerzy W.; Norrby, Per-Ola

    2001-01-01

    The protonation states of a series of piperidinedicarboxylic acids (PDAs), which are conformationally constrained acidic alpha -amino acids, have been studied by C-13 NMR titration in water. The resulting data have been correlated with theoretical results obtained by HF/6-31+G* calculations using...

  20. Characterization of 3alpha-acetyl-11-keto-alpha-boswellic acid, a pentacyclic triterpenoid inducing apoptosis in vitro and in vivo.

    Science.gov (United States)

    Büchele, Berthold; Zugmaier, Waltraud; Estrada, Aidee; Genze, Felicitas; Syrovets, Tatiana; Paetz, Christian; Schneider, Bernd; Simmet, Thomas

    2006-11-01

    3Alpha-acetyl-11-keto-alpha-boswellic acid (3alpha-acetoxy-11-oxo-olean-12-en-24-oic acid, 1) was synthesized by a radical-type reaction using bromine and 3alpha-acetyl-alpha-boswellic acid isolated from the oleo-gum-resin of Boswellia carterii. 1D and 2D NMR (COSY, HMBC, ROESY) at 500 MHz were used for shift assignments and structure verification. The compound investigated is present in a herbal preparation extracted from Boswellia serrata oleo-gum-resin, it inhibits the growth of chemotherapy-resistant human PC-3 prostate cancer cells in vitro and induces apoptosis as shown by activation of caspase 3 and the induction of DNA fragmentation. In addition, compound 1 is active IN VIVO as shown by inhibition of proliferation and induction of apoptosis in PC-3 prostate cancer cells xenotransplanted onto the chick chorioallantoic membrane.

  1. Asthma induction in mice leads to appearance of alpha2-3- and alpha2-6-linked sialic acid residues in respiratory goblet-like cells

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Jensen, Niels-Erik Viby; Mandel, Ulla;

    2008-01-01

    to demonstrate binding of lectins and antibodies that detect alpha2-3- and alpha2-6-linked sialic acid residues. After sensitization and challenge, the histology of the lung changed markedly, and goblet-like cells appeared, most likely caused by Clara cell metaplasia. Normal Clara cells showed no reaction after......Allergic asthmatic inflammation in mice was induced by sensitization with ovalbumin and lipopolysaccharide from Escherichia coli and visualized in the airways of asthmatic mice by spatial and temporal changes of carbohydrates containing sialic acid residues. Immunohistochemistry was used...... incubation with the sialic acid detecting agents, while the goblet-like cells expressed both alpha2-3- and alpha2-6-linked sialic acid residues in the asthmatic animals. The lectins but not the antibodies reacted with intestinal goblet cells. Instead, an antibody recognizing a disialoganglioside, stained...

  2. Transport of. cap alpha. -aminoisobutyric acid into rat parotid after X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bodner, Lipa

    1989-04-01

    Rat parotid gland exposed to 20 Gy X-irradiation exhibits functional alteration 3 days after exposure. The flow rate of saliva and the uptake of ..cap alpha..-aminoisobutyric acid by the gland was reduced to 50% of values for the control non-irradiated glands. When the same gland was studied in an in vitro system it functioned normally. K/sup +/ release and ..cap alpha..-aminoisobutyric acid uptake by the irradiated dispersed acinar cells was comparable to the control. Transport alteration from the circulatory system into the parotid gland may cause the initial radiation-induced damage.

  3. N-terminal amino acid sequence of Bacillus licheniformis alpha-amylase: comparison with Bacillus amyloliquefaciens and Bacillus subtilis Enzymes.

    OpenAIRE

    Kuhn, H.; Fietzek, P P; Lampen, J O

    1982-01-01

    The thermostable, liquefying alpha-amylase from Bacillus licheniformis was immunologically cross-reactive with the thermolabile, liquefying alpha-amylase from Bacillus amyloliquefaciens. Their N-terminal amino acid sequences showed extensive homology with each other, but not with the saccharifying alpha-amylases of Bacillus subtilis.

  4. Mitochondrial complex II participates in normoxic and hypoxic regulation of alpha-keto acids in the murine heart.

    NARCIS (Netherlands)

    Muhling, J.; Tiefenbach, M.; Lopez-Barneo, J.; Piruat, J.I.; Garcia-Flores, P.; Pfeil, U.; Gries, B.; Muhlfeld, C.; Weigand, M.A.; Kummer, W.; Weissmann, N.; Paddenberg, R.

    2010-01-01

    alpha-Keto acids (alpha-KAs) are not just metabolic intermediates but are also powerful modulators of different cellular pathways. Here, we tested the hypothesis that alpha-KA concentrations are regulated by complex II (succinate dehydrogenase=SDH), which represents an intersection between the mitoc

  5. Chemical reactivity of {alpha}-isosaccharinic acid in heterogeneous alkaline systems

    Energy Technology Data Exchange (ETDEWEB)

    Glaus, M. A.; Loon, L. R. Van

    2009-05-15

    Cellulose degradation under alkaline conditions is of relevance for the mobility of many radionuclides in the near-field of a cementitious repository for radioactive waste, because metal-binding degradation products may be formed. Among these, {alpha}- isosaccharinic acid ({alpha}-ISA) is the strongest complexant. The prediction of the equilibrium concentration of {alpha}-ISA in cement pore water is therefore an important step in the assessment of the influence of cellulose degradation products on the speciation of radionuclides in such environments. The present report focuses on possible chemical transformation reactions of {alpha}-ISA in heterogeneous alkaline model systems containing either Ca(OH){sub 2} or crushed hardened cement paste. The transformation reactions were monitored by measuring the concentration of {alpha}-ISA by high performance anion exchange chromatography and the formation of reaction products by high performance ion exclusion chromatography. The overall loss of organic species from solution was monitored by measuring the concentration of non-purgeable organic carbon. The reactions were examined in diluted and compacted suspensions, at either 25 {sup o}C or 90 {sup o}C, and under anaerobic atmospheres obtained by various methods. It was found that {alpha}-ISA was transformed under all conditions tested to some extent. Reaction products, such as glycolate, formate, lactate and acetate, all compounds with less complexing strength than {alpha}-ISA, were detected. The amount of reaction products identified by the chromatographic technique applied was {approx} 50 % of the amount of {alpha}-ISA reacted. Sorption of {alpha}-ISA to Ca(OH){sub 2} contributed only to a minor extent to the loss of {alpha}-ISA from the solution phase. As the most important conclusion of the present work it was demonstrated that the presence of oxidising agents had a distinctive influence on the turnover of {alpha}-ISA. Under aerobic conditions {alpha}-ISA was

  6. The clinical efficacy of Methylprednisolone pulse combined Lipoic Acid therapy on different types of multiple sclerosis%甲基强的松龙冲击联合硫辛酸疗法对不同类型多发性硬化的疗效观察

    Institute of Scientific and Technical Information of China (English)

    蒲志勇; 柯莎

    2011-01-01

    目的 比较甲基强的松龙(methylprednisolone,MP)冲击疗法和甲基强的松龙冲击联合硫辛酸(Lipoic acid,LA)疗法对不同类型多发性硬化(multiple sclerosis,MS)的近期疗效.方法 MP组以MP冲击3 d后,剂量减半并改为口服,每3天减半量,直至减完;MP+LA组MP用法与MP组相同,但从口服起,即加服α-LA胶囊,连续14 d.结果 两种疗法在观察期内对迅速缓解复发-缓解型症状均有显著疗效;对于继发进展型MP疗法在观察期内并未取得显著疗效,而MP +LA疗法取得显著疗效.结论 提示MP +LA可能在近期内对改善继发进展型症状较单用MP冲击显著有效.

  7. α-硫辛酸和维生素C对慢性砷染毒大鼠氧化应激的保护作用%Effects of α-lipoic acid and vitamin C on oxidative stress in rat exposed to chronic arsenic toxicity

    Institute of Scientific and Technical Information of China (English)

    刘重斌; 冯彦红; 叶光华; 肖敏

    2010-01-01

    饮水砷毒性有重要作用.%Objective To explore arsenic-induced oxidative stress and the protective efficacy of α-lipoic acid and vitamin c.Methods 50 male SD rats were randomly divided into 5 groups.Ten rats(the control group)were exposed to deionized water for 6 weeks, and the others were alone exposed to sodium arsenite (50 mg/L water)for 6 weeks, at the same time, three group rats were administered intragastrically(I.g.)with α-lipoic acid 10 mg· kg-1· d-1 and vitamin C 25 mg· kg-1· d-1 either alone or in combination.At the end of experiment, blood was drawn from abdominal aorta, and then the blood, brain and liver of rats were used for biochemical assays, including blood glutathione(GSH), δ-aminolevulinic acid dehydratase(δ-ALAD), reactive oxygen species(ROS)and oxidized glutathione(GSSG)level.At the same time, the super oxide dismutase(SOD)activity, glutathione peroxidase(GSH-Px)activity, catalase(CAT)activity, ATPase activity of brain and liver were determined.The caspase activity of brain were also determined.Results There were a significant increase in ROS level(P<0.05), but a significant decrease in δ-ALAD activity(P<0.01)in the chronic arsenic toxicity model group compared with the control group.These alterations were marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in rat(P<0.05).At the same time, there was a significant increase in the ROS and TBARS level of the brain and liver(P<0.05), and caspase activity of the brain(P<0.05), while there was a significant decrease in antioxidant enzymes and ATPase activity on arsenite exposure in rats(P<0.05).These alterations were also marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite

  8. Effect of temperature on the dilution enthalpies of {alpha},{omega}-amino acids in aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Romero, C.M., E-mail: cmromeroi@unal.edu.co [Departamento de Quimica, Facultad de Ciencias, Universidad Nacional de Colombia, Bogota (Colombia); Cadena, J.C., E-mail: jccadena@unal.edu.co [Departamento de Quimica, Facultad de Ciencias, Universidad Nacional de Colombia, Bogota (Colombia); Lamprecht, I., E-mail: ingolf.lamprecht@t-online.de [Institut fuer Biologie, Freie Universitaet Berlin, Berlin (Germany)

    2011-10-15

    Highlights: > The dilution of 3-amino propanoic acid, 4-amino butanoic acid, 5-amino pentanoic acid, and 6-amino hexanoic acid in water is an exothermic process at T = (293.15, 298.15, 303.15, and 308.15) K. > The limiting experimental slopes of the enthalpies of dilution with respect to the molality change {Delta}m, are negative suggesting that the solutes interact with water primarily through their alkyl groups. > The value of the pairwise coefficient is positive at the temperatures considered, and the magnitude increases linearly with the number of methylene groups. > The comparison between the pairwise interaction coefficients for {alpha},{omega}-amino acids and {alpha}-amino acids shows that the change in the enthalpic interaction coefficient is related to the relative position of the polar groups. - Abstract: Dilution enthalpies of aqueous solutions of 3-amino propanoic acid, 4-amino butanoic acid, 5-amino pentanoic acid, and 6-amino hexanoic acid were determined at T = (293.15, 298.15, 303.15, and 308.15) K using an LKB flow microcalorimeter. The homotactic interaction coefficients were obtained according to the McMillan-Mayer theory from the experimental data. For all the systems studied, the dilution of {alpha},{omega}-amino acids in water is an exothermic process; the pair coefficients have positive values which increases with chain length. The obtained values of the interaction coefficients are interpreted in terms of solute-solvent and solute-solute interactions and are used as indicative of hydrophobic behavior of the amino acid studied.

  9. Regulation of bile acid synthesis by the nuclear receptor Rev-erb alpha

    NARCIS (Netherlands)

    Duez, Helene; Van Der Veen, Jelske N.; Duhem, Christian; Pourcet, Benoit; Touvier, Thierry; Fontaine, Coralie; Derudas, Bruno; Bauge, Eric; Havinga, Rick; Bloks, Vincent W.; Wolters, Henk; Van Der Sluijs, Fjodor H.; Vennstrom, Bjorn; Kuipers, Folkert; Staels, Bart

    2008-01-01

    Background & Aims: Conversion into bile acids represents an important route to remove excess cholesterol from the body. Rev-erb alpha is a nuclear receptor that participates as one of the clock genes in the control of circadian rhythmicity and plays a regulatory role in lipid metabolism and adipogen

  10. Alpha 1-acid glycoprotein has immunomodulatory effects in neonatal swine adipose tissue

    Science.gov (United States)

    Alpha 1-acid glycoprotein (AGP) is the most abundant protein in serum of neonatal swine. This protein functions as an immunomodulator in the pig. Recent work has demonstrated that adipose tissue can express AGP mRNA, as well as numerous cytokine mRNA. The present study was designed to determine i...

  11. Regulation of the synthesis of barley aleurone. cap alpha. -amylase by gibberellic acid and calcium ions

    Energy Technology Data Exchange (ETDEWEB)

    Jones, R.L.; Carbonell, J.

    1984-09-01

    The effects of gibberellic acid (GA/sub 3/) and calcium ions on the production of ..cap alpha..-amylase and acid phosphatase by isolated aleurone layers of barley (Hordeum vulgare L. cv Himalaya) were studied. Aleurone layers not previously exposed to GA/sub 3/ or CA/sup 2 +/ show qualitative and quantitative changes in hydrolase production following incubation in either GA/sub 3/ or CA/sup 2 +/ or both. In cubation in H/sub 2/O or CA/sup 2 +/ results in the production of low levels of ..cap alpha..-amylase or acid phosphatase. The addition of GA/sub 3/ to the incubation medium causes 10- to 20-fold increase in the amounts of these enzymes released from the tissue, and addition of CA/sup 2 +/ at 10 millimolar causes a further 8- to 9-fold increase in ..cap alpha..-amylase release and a 75% increase in phosphatase release. Production of ..cap alpha..-amylase isoenzymes is also modified by the levels of GA/sub 3/ and CA/sup 2 +/ in the incubation medium. ..cap alpha..-amylase 2 is produced under all conditions of incubation, while ..cap alpha..-amylase 1 appears only when layers are incubated in GA/sub 3/ or GA/sub 3/ plus CA/sup 2 +/. The synthesis of ..cap alpha..-amylases 3 and 4 requires the presence of both GA/sub 3/ and CA/sup 2 +/ in the incubation medium. Laurell rocket immunoelectrophoresis shows that two distinct groups of ..cap alpha..-amylase antigens are present in incubation media of aleurone layers incubated with both GA/sub 3/ and CA/sup 2 +/, while only one group of antigens is found in media of layers incubated in GA/sub 3/ alone. Strontium ions can be substituted for CA/sup 2 +/ in increasing hydrolase production, although higher concentrations of Sr/sup 2 +/ are requried for maximal response. We conclude that GA/sub 3/ is required for the production of ..cap alpha..-amylase 1 and that both GA/sub 3/ and either CA/sup 2 +/ or Sr/sup 2 +/ are required for the production of isoenzymes 3 and 4 of barley aleurone ..cap alpha..-amylase. 22 references, 8

  12. Regulation of hepatic branched-chain alpha-keto acid dehydrogenase complex in rats fed a high-fat diet

    Science.gov (United States)

    Objective: Branched-chain alpha-keto acid dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of branched chain alpha-ketoacid (BCKA) catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal...

  13. Stability of HAMLET--a kinetically trapped alpha-lactalbumin oleic acid complex.

    Science.gov (United States)

    Fast, Jonas; Mossberg, Ann-Kristin; Svanborg, Catharina; Linse, Sara

    2005-02-01

    The stability toward thermal and urea denaturation was measured for HAMLET (human alpha-lactalbumin made lethal to tumor cells) and alpha-lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than alpha-lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15 degrees C lower for apo HAMLET than for apo alpha-lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than alpha-lactalbumin, although it is a complex of alpha-lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol.

  14. Phenylalanine Aminomutase-Catalyzed Addition of Ammonia to Substituted Cinnamic Acids : a Route to Enantiopure alpha- and beta-Amino Acids

    NARCIS (Netherlands)

    Szymanski, Wiktor; Wu, Bian; Weiner, Barbara; de Wildeman, Stefaan; Feringa, B.L.; B. Janssen, Dick

    2009-01-01

    An approach is described for the synthesis of aromatic alpha- and beta-amino acids that Uses phenylalanine aminomutase to catalyze a highly enantioselective addition of ammonia to substituted cinnamic acids. The reaction has a broad scope and yields Substituted alpha- and beta-phenylalanines with ex

  15. Interference from alpha-amino acid and protein on determination of formaldehyde in food

    Science.gov (United States)

    Lu, Xiumin; Zhang, Xiaofeng; Fu, Yujie; Xiang, Jinxin

    2005-12-01

    The disturbance of alpha-amino acids and proteins on the analysis of formaldehyde content in food was investigated by electrochemical assay. Results show that the pH decreases gradually from 9.91 to 4.36 with increasing aspartic acid concentration. The recovery rate changes from 8% to 100% after different amounts of formaldehyde were added into protein solutions. For edible bamboo shoots, the recovery rate of formaldehyde is 80% to 100%. For shrimp kernel, however, the recovery rate of formaldehyde is 8% to 60%. These results indicate that the consumed quantity of formaldehyde is correlative with the protein concentration in foods. Therefore, the determinate formaldehyde content in food is actually not the totally applied amount, but just the residue after its reaction with the alpha-amino acids or free amino groups on the protein surface.

  16. Structure and characterisation of a duplicated human alpha 1 acid glycoprotein gene.

    Science.gov (United States)

    Merritt, C M; Board, P G

    1988-06-15

    Human alpha 1-acid glycoprotein (AGP), also known as orosomucoid, is a major acute-phase plasma protein. The amino acid sequence of AGP, which was determined by sequencing from protein isolated from pooled plasma, contained amino acid substitutions in 21 different positions. Genomic and cDNA clones which correspond to one of the possible amino acid sequences have been previously reported. In this paper we present the complete nucleotide sequence of a second gene, AGP2 which is located approx. 3.3 kb downstream from AGP1. The derived amino acid sequence of AGP2 contains 19 of the possible alternative amino acid substitutions as well as two additional differences. It is clear from the results presented here that the AGP in human plasma is the product of two separate gene loci.

  17. alpha-Amylase gene of Streptomyces limosus: nucleotide sequence, expression motifs, and amino acid sequence homology to mammalian and invertebrate alpha-amylases.

    OpenAIRE

    1987-01-01

    The nucleotide sequence of the coding and regulatory regions of the alpha-amylase gene (aml) of Streptomyces limosus was determined. High-resolution S1 mapping was used to locate the 5' end of the transcript and demonstrated that the gene is transcribed from a unique promoter. The predicted amino acid sequence has considerable identity to mammalian and invertebrate alpha-amylases, but not to those of plant, fungal, or eubacterial origin. Consistent with this is the susceptibility of the enzym...

  18. Sorption of aqueous carbonic, acetic, and oxalic acids onto alpha-alumina.

    Science.gov (United States)

    Alliot, Cyrille; Bion, Lionel; Mercier, Florence; Toulhoat, Pierre

    2005-07-15

    The presence of organic complexing agents can modify the behavior of a surface. This study aims to better understand the impact of carboxylic acids (acetic, oxalic, and carbonic acids) issued from cellulose degradation and equally naturally present in soils. First, evidence of two different kinds of sites for chloride adsorption onto alpha-alumina and another for sodium sorption was provided. Consequently, no competition between these cation and anion sorptions occurs on alpha-alumina. The associated exchange capacities and ionic exchange constants were measured. Second, the adsorption behavior of the carboxylic acids was studied as a function of aqueous -log[H(+)] and 0.01 to 0.1 M ionic strength (NaCl), and modeled by using mass action law for ideal biphasic systems. The carboxylic acids were found to be adsorbed on the same sites as chloride ions. The competition between organic ligands and chloride ions was satisfactorily accounted for by the model assuming the deprotonated form of the ligands was sorbed on alpha-alumina. The model also allowed us to interpret the adsorption of all species under various conditions without any extra fitting parameters.

  19. Isolation of linoleic and alpha-linolenic acids as COX-1 and -2 inhibitors in rose hip

    DEFF Research Database (Denmark)

    Jäger, Anna; Petersen, K N; Thomasen, G.;

    2008-01-01

    /2 activity-guided. The bioassay-guided fractionation led to the isolation of linoleic acid (the IC50 for COX-1 was 85 microm and 0.6 microM for COX-2) and alpha-linolenic acid (the IC50 for COX-1 was 52 microM and 12 microM for COX-2). The COX-2/COX-1 ratio was 0.007 for linoleic acid and 0.2 for alpha...

  20. Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Rino [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Murota, Kaeko [Department of Life Science, School of Science and Engineering, Kinki University, Osaka 770-8503 (Japan); Yamada, Yuko [Laboratory of Physiological Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Moriyama, Tatsuya [Department of Applied Cell Biology, Graduate School of Agriculture, Kinki University, Nara 631-8505 (Japan); Goto, Tsuyoshi; Kawada, Teruo [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-06-24

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and

  1. Phytanic acid oxidation: normal activation and transport yet defective alpha-hydroxylation of phytanic acid in peroxisomes from Refsum disease and rhizomelic chondrodysplasia punctata.

    Science.gov (United States)

    Pahan, K; Khan, M; Singh, I

    1996-05-01

    In humans the oxidation of phytanic acid is a peroxisomal function. To understand the possible mechanisms for the pathognomic accumulation of phytanic acid in plasma and body fluids of Refsum disease (RD) and rhizomelic chondrodysplasia punctata (RCDP), we investigated activities of various steps (activation, transport, and oxidation) in the metabolism of phytanic acid in peroxisomes isolated from cultured skin fibroblasts from control, RD, and RCDP subjects. Activation of phytanic acid was normal in peroxisomes from both RD and RCDP. Transport of phytanic acid or phytanoyl-CoA in the absence or presence of fatty acid activating cofactors (ATP, MgCl2, and CoASH) into peroxisomes isolated from RD and RCDP skin fibroblasts was also similar to that of peroxisomes from control fibroblasts. Defective oxidation of [(2,3)-3H]- or [1-14C]phytanic acid, or [1-14C]phytanoyl-CoA (substrate for the first step of alpha-oxidation) but normal oxidation of [1-14C] alpha-hydroxyphytanic acid (substrate for the second step of the alpha-oxidation pathway) in peroxisomes from RD clearly demonstrates that excessive accumulation of phytanic acid in plasma and body fluids of RD is due to the deficiency of phytanic acid alpha-hydroxylase in peroxisomes. However, in RCDP peroxisomes, in addition to deficient oxidation of [1-14C]phytanic acid or phytanoyl-CoA or [(2,3)-3H]phytanic acid, the oxidation of [1-14C] alpha-hydroxyphytanic acid was also deficient, indicating that in RCDP the activities both of alpha-hydroxylation of phytanic acid and decarboxylation of alpha-hydroxyphytanic acid are deficient. These observations indicate that peroxisomal membrane functions (phytanic acid activation and transport) in phytanic acid metabolism are normal in both RD and RCDP. The defect in RD is in the alpha-hydroxylation of phytanic acid; whereas in RCDP both alpha-hydroxylation of phytanic acid as well as decarboxylation of alpha-hydroxyphytanic acid are deficient.

  2. Biotechnological production of alpha-keto acids: Current status and perspectives.

    Science.gov (United States)

    Song, Yang; Li, Jianghua; Shin, Hyun-Dong; Liu, Long; Du, Guocheng; Chen, Jian

    2016-11-01

    Alpha-keto (α-keto) acids are used widely in feeds, food additives, pharmaceuticals, and in chemical synthesis processes. Although most α-keto acids are currently produced by chemical synthesis, their biotechnological production from renewable carbohydrates is a promising new approach. In this mini-review, we first present the different types of α-keto acids as well as their applications; next, we summarize the recent progresses in the biotechnological production of some important α-keto acids; namely, pyruvate, α-ketoglutarate, α-ketoisovalerate, α-ketoisocaproate, phenylpyruvate, α-keto-γ-methylthiobutyrate, and 2,5-diketo-d-gluconate. Finally, we discuss the future prospects as well as favorable directions for the biotechnological production of keto acids that ultimately would be more environment-friendly and simpler compared with the production by chemical synthesis.

  3. Refsum disease: a defect in the alpha-oxidation of phytanic acid in peroxisomes.

    Science.gov (United States)

    Singh, I; Pahan, K; Singh, A K; Barbosa, E

    1993-10-01

    The oxidation of phytanic acid to pristanic acid was previously demonstrated to be deficient in monolayer cultures of skin fibroblasts (Herndon et al. 1969. J. Clin. Invest. 48: 1017-1032). However, identification of subcellular organelle with deficient enzyme activity has not been established. To define the subcellular organelle with deficient enzyme activity in the catabolism of phytanic acid, we measured the oxidation of [1-14C] phytanic acid to 14CO2 and pristanic acid in different subcellular organelles isolated from cultured skin fibroblasts from control and Refsum patients. The rates of oxidation of phytanic acid in peroxisomes, mitochondria, and endoplasmic reticulum were 37.1 +/- 2.65, 1.9 +/- 0.3, and 0.4 +/- 0.07 pmol/h per mg protein, respectively, from control fibroblasts. The phytanic acid oxidation activity in mitochondria (2.04 +/- 0.7 pmol/h per mg protein) and endoplasmic reticulum (0.43 +/- 0.2 pmol/h per mg protein) from Refsum fibroblasts was similar to control fibroblasts. However, phytanic acid oxidation in peroxisomes from Refsum fibroblasts was not detected at all the protein concentrations tested. On the other hand, the peroxisomes from Refsum fibroblasts had normal rates of activation and oxidation of palmitic and lignoceric acids, suggesting that the peroxisomes isolated from Refsum fibroblasts were metabolically active. The phytanoyl-CoA ligase, the first enzyme in the alpha-oxidation pathway, had activity similar to that in peroxisomes from control (9.86 +/- 0.09 nmol/h per mg protein) and Refsum (10.25 +/- 0.31 nmol/h per mg protein) fibroblasts. The data described here clearly demonstrate that pathognomonic accumulation of phytanic acid in patients with Refsum disease is due to the deficient activity of peroxisomal alpha-oxidation enzyme system.

  4. Enzymatic synthesis of enantiopure alpha- and beta-amino acids by phenylalanine aminomutase-catalysed amination of cinnamic acid derivatives.

    Science.gov (United States)

    Wu, Bian; Szymanski, Wiktor; Wietzes, Piet; de Wildeman, Stefaan; Poelarends, Gerrit J; Feringa, Ben L; Janssen, Dick B

    2009-01-26

    The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of alpha-phenylalanine to beta-phenylalanine, an important step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)-cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring-substituted (E)-cinnamic acids can serve as a substrate in PAM-catalysed ammonia addition reactions for the biocatalytic production of several important beta-amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non-natural aromatic alpha- and beta-amino acids in excellent enantiomeric excess (ee >99 %). The internal 5-methylene-3,5-dihydroimidazol-4-one (MIO) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.

  5. a-硫辛酸联合甲钴胺治疗2型糖尿病周围神经病变的临床观察%Clinical observation of a-lipoic acid combined with mecobalamin on diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    林远; 张帆(通讯作者); 韩令川; 彭卫群; 谢谦

    2013-01-01

      目的:观察a-硫辛酸(ALA)联合甲钴胺对2型糖尿病患者周围神经病变的疗效。方法:筛查2型糖尿病周围神经病变患者80例,随机分为两组。治疗组40例予ALA联合甲钴胺治疗2周,对照组40例予甲钴胺治疗2周。分别于治疗前后进行症状总评分(TSS)评分及测定血清C反应蛋白(CRP)。结果:治疗组的TSS评分较对照组改善明显,治疗组的CRP水平较对照组下降明显(P均<0.05)。结论:ALA联合甲钴胺治疗糖尿病周围神经病变效果明显。%Objective To evaluate the effect of the therapy of a-lipoic acid combined with mecobalamin on diabetic peripheral neuropathy(DPN). Methods 80 type 2 diabetic patients complicated with DPN were randomly divided into 2 groups: treatment group(n=40),receiving ALA combined with mecobalamin therapy for 2 weeks;and control group(n=40),receiving mecobalamin therapy for 2 weeks.Total symptom score(TSS) were used to evaluate ,CRP was measured before and after the therapy. Results Compaired with the control group ,the TSS of the treatment group were improved better, the level of CRP was reduced significantly(both P<0.05).Conclusions ALA combined with mecobalamin effectively improve the symptom of DPN patients.

  6. Retinol, alpha-tocopherol and fatty acid content in Bulgarian black Sea fish species

    OpenAIRE

    Stancheva, M; Galunska, B.; Dobreva, A. D.; Merdzhanova, A.

    2012-01-01

    The aim of the present study was to measure and evaluate the total lipids, fatty acid profile, retinol content and alpha-tocopherol content in the edible tissue of four commercially important fish species from the Bulgarian Black sea: Sprat (Sprattus sprattus), Round Goby (Neogobius rattan), Black Sea Horse Mackerel (Trahurus medditeraneus ponticus) and Shad (Alosa pontica). Fat soluble vitamins were analyzed simultaneously usi...

  7. Effect ofα-lipoic Acid on Islet Beta Cell Function and Oxidative Stress in Patients with New Di-agnosed Type 2 Diabetes Mellitus%α-硫辛酸对初诊2型糖尿病患者胰岛β细胞功能及氧化应激指标的影响

    Institute of Scientific and Technical Information of China (English)

    张运捷; 王镜雯; 宋波; 何慧君; 吴广飞; 刘博伟

    2014-01-01

    【目的】评价α-硫辛酸对初诊2型糖尿病(T2DM)患者胰岛β细胞功能及氧化应激水平影响。【方法】将2013年3~9月秦皇岛市第一医院的80例初诊T2DM患者随机分为A、B两组,均行胰岛素泵强化治疗2周,A组同时静脉输注α-硫辛酸。治疗前及治疗2周后检测两组患者的血糖、血脂,采用稳态模型(HOMA)计算胰岛β细胞功能指数(HOMA-β),酶联免疫吸附法检测尿8-异前列腺素 F2α(8-isoPGE),评价氧化应激水平。【结果】治疗后,A组 HOMA-β显著高于B组(P<0.05),8-isoPGF分泌率[F2α(8-isoPGE)/Cr]显著低于B组(P<0.05),F2α(8-isoPGE)/Cr与餐后2 h血糖(2hPG)(r=0.432,P<0.01)、总胆固醇(TC)(r =0.315,P <0.01)、体质量指数(BMI)(r =0.256,P <0.05)呈正相关,与 HOMA-β(r =-0.217,P<0.05)呈负相关。2hPG是尿F2α(8-isoPGE)/Cr的独立危险因素。【结论】应用α-硫辛酸可改善初诊T2DM患者胰岛β细胞功能,降低氧化应激水平。%[Obj ective]To evaluate the effect ofα-lipoic acid on islet beta cell function and oxidative stress in patients with new diagnosed type 2 diabetes mellitus(T2DM).[Methods]Totally 80 patients with new di-agnosed T2DM in first hospital of Qinhuangdao city from March 2013 to Sept.2013 were randomly divided in-to group A and group B.All patients were given insulin pump intensification therapy for 2 weeks.Group A was simultaneously treated with intravenous infusion ofα-lipoic acid.Blood glucose and lipids of two groups were measured before and 2 weeks after treatment.Islet beta cell function index(HOMA-β)was calculated by using steady state model(HOMA).Enzyme linked immunosorbent assay was used to detect urine 8-isoprostan-es F2α(8-isoPGE).Oxidative stress was assessed.[Results]After treatment,HOMA-βin group A was higher than that in group B(P<0.05),while urine F2α(8-isoPGE)/Cr in

  8. The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis.

    Science.gov (United States)

    Lehman, John J; Boudina, Sihem; Banke, Natasha Hausler; Sambandam, Nandakumar; Han, Xianlin; Young, Deanna M; Leone, Teresa C; Gross, Richard W; Lewandowski, E Douglas; Abel, E Dale; Kelly, Daniel P

    2008-07-01

    High-capacity mitochondrial ATP production is essential for normal function of the adult heart, and evidence is emerging that mitochondrial derangements occur in common myocardial diseases. Previous overexpression studies have shown that the inducible transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is capable of activating postnatal cardiac myocyte mitochondrial biogenesis. Recently, we generated mice deficient in PGC-1alpha (PGC-1alpha(-/-) mice), which survive with modestly blunted postnatal cardiac growth. To determine if PGC-1alpha is essential for normal cardiac energy metabolic capacity, mitochondrial function experiments were performed on saponin-permeabilized myocardial fibers from PGC-1alpha(-/-) mice. These experiments demonstrated reduced maximal (state 3) palmitoyl-l-carnitine respiration and increased maximal (state 3) pyruvate respiration in PGC-1alpha(-/-) mice compared with PGC-1alpha(+/+) controls. ATP synthesis rates obtained during maximal (state 3) respiration in permeabilized myocardial fibers were reduced for PGC-1alpha(-/-) mice, whereas ATP produced per oxygen consumed (ATP/O), a measure of metabolic efficiency, was decreased by 58% for PGC-1alpha(-/-) fibers. Ex vivo isolated working heart experiments demonstrated that PGC-1alpha(-/-) mice exhibited lower cardiac power, reduced palmitate oxidation, and increased reliance on glucose oxidation, with the latter likely a compensatory response. (13)C NMR revealed that hearts from PGC-1alpha(-/-) mice exhibited a limited capacity to recruit triglyceride as a source for lipid oxidation during beta-adrenergic challenge. Consistent with reduced mitochondrial fatty acid oxidative enzyme gene expression, the total triglyceride content was greater in hearts of PGC-1alpha(-/-) mice relative to PGC-1alpha(+/+) following a fast. Overall, these results demonstrate that PGC-1alpha is essential for the maintenance of maximal, efficient cardiac

  9. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    Science.gov (United States)

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

  10. Antifungal properties of alpha,omega-alkanedicarboxylic acids and their dimethyl esters.

    Science.gov (United States)

    Gershon, H; Shanks, L

    1976-08-01

    Thirteen alpha, omega-alkanedicarboxylic acids (C2-C12, C14, and C16) and their dimethyl esters were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabourauc dextrose agar at pH 4.0 AND 5.6. Toxicity to Canadida albicans, Trichophyton mentagrophytes, and Mucor mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The dicarboxylic acids possessed very poor to no antifungal activity against all six fungi. The fungitoxicity of the dimethyl esters to A. niger, T. viride, and M. verrucaria was C8 = C9 greater than C7 greater than C6 = C5 greater than C10 greater than C4 greater than C11 and to C. albicans, T. mentagrophytes, and M. mucedo C9 greater than C10 greater than C11 greater than C12 = C8 greater than C7 greater than C6 greater than C5 greater than C4 greater than C3. The fungitoxicity of the esters of fatty acids and alpha-omega-alkanedicarboxylic acids was influenced by chain length and not by the pH of the medium or the absence or presence of beef serum.

  11. Reactivity of the Monoterpenoid Nerol with p-Toluenesulfonic and Chlorosulfonic Acids: Selective Syntheses of alpha-Terpineol and alpha-Cyclogeraniol. An Activity for the Undergraduate Organic Lab

    Science.gov (United States)

    Linares-Palomino, Pablo J.; Salido, Sofia; Altarejos, Joaquin; Nogueras, Manuel; Sanchez, Adolfo

    2006-01-01

    The selective syntheses of the cyclic monoterpenoids alpha-terpineol or alpha-cyclogeraniol from the acyclic monoterpenoid nerol using p-toluenesulfonic acid or chlorosulfonic acid as cyclizing agents, respectively, are described. The different behavior of nerol under diverse experimental conditions such as nature of the acid agents, solvents, and…

  12. Tertiary structure of human alpha1-acid glycoprotein (orosomucoid). Straightforward fluorescence experiments revealing the presence of a binding pocket.

    Science.gov (United States)

    Albani, Jihad R

    2004-02-25

    Binding of hemin to alpha1-acid glycoprotein has been investigated. Hemin binds to the hydrophobic pocket of hemoproteins. The fluorescent probe 2-(p-toluidino)-6-naphthalenesulfonate (TNS) binds to a hydrophobic domain in alpha1-acid glycoprotein with a dissociation constant equal to 60 microM. Addition of hemin to an alpha1-acid glycoprotein-TNS complex induces the displacement of TNS from its binding site. At saturation (1 hemin for 1 protein) all the TNS has been displaced from its binding site. The dissociation constant of hemin-alpha1-acid glycoprotein was found equal to 2 microM. Thus, TNS and hemin bind to the same hydrophobic site: the pocket of alpha1-acid glycoprotein. Energy-transfer studies performed between the Trp residues of alpha1-acid glycoprotein and hemin indicated that efficiency (E) of Trp fluorescence quenching was equal to 80% and the Förster distance, R0 at which the efficiency of energy transfer is 50% was calculated to be 26 A, revealing a very high energy transfer.

  13. Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity.

    Science.gov (United States)

    Naiyanetr, Phornnop; Butler, Jeffrey D; Meng, Liping; Pfeiff, Janice; Kenny, Thomas P; Guggenheim, Kathryn G; Reiger, Roman; Lam, Kit; Kurth, Mark J; Ansari, Aftab A; Coppel, Ross L; López-Hoyos, Marcos; Gershwin, M Eric; Leung, Patrick S C

    2011-11-01

    Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure-activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coupled to bovine serum albumin (BSA), induces anti-mitochondrial antibodies (AMAs) and cholangitis. Based upon these data, we have focused on covalent modifications of the lipoic acid disulfide ring and subsequent analysis of such xenobiotics coupled to a 15mer of PDC-E2 for immunoreactivity against a broad panel of sera from patients with PBC and controls. Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S-S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. This observation is particularly significant in light of the function of the lipoyl moiety in electron transport of which the catalytic disulfide constantly opens and closes and, thus, raises the intriguing thesis that common electrophilic agents, i.e. acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs), may lead to xenobiotic modification in genetically susceptible individuals that results in the generation of AMAs and ultimately clinical PBC.

  14. Sulfate- and sialic acid-containing glycolipids inhibit DNA polymerase alpha activity.

    Science.gov (United States)

    Simbulan, C M; Taki, T; Tamiya-Koizumi, K; Suzuki, M; Savoysky, E; Shoji, M; Yoshida, S

    1994-03-16

    The effects of various glycolipids on the activity of immunoaffinity-purified calf thymus DNA polymerase alpha were studied in vitro. Preincubation with sialic acid-containing glycolipids, such as sialosylparagloboside (SPG), GM3, GM1, and GD1a, and sulfatide (cerebroside sulfate ester, CSE) dose-dependently inhibited the activity of DNA polymerase alpha, while other glycolipids, as well as free sphingosine and ceramide did not. About 50% inhibition was achieved by preincubating the enzyme with 2.5 microM of CSE, 50 microM of SPG or GM3, and 80 microM of GM1. Inhibition was noncompetitive with both the DNA template and the substrate dTTP, as well as with the other dNTPs. Since the inhibition was largely reversed by the addition of 0.05% Nonidet P40, these glycolipids may interact with the hydrophobic region of the enzyme protein. Apparently, the sulfate moiety in CSE and the sialic acid moiety in gangliosides were essential for the inhibition since neither neutral glycolipids (i.e., glucosylceramide, galactosylceramide, lactosylceramide) nor asialo-gangliosides (GA1 and GA2) showed any inhibitory effect. Furthermore, the ceramide backbone was also found to be necessary for maximal inhibition since the inhibition was largely abolished by substituting the lipid backbone with cholesterol. Increasing the number of sialic acid moieties per molecule further enhanced the inhibition, while elongating the sugar chain diminished it. It was clearly shown that the N-acetyl residue of the sialic acid moiety is particularly essential for inhibition by both SPG and GM3 because the loss of this residue or substitution with a glycolyl residue completely negated their inhibitory effect on DNA polymerase alpha activity.

  15. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

    Directory of Open Access Journals (Sweden)

    Somoza Veronika

    2009-02-01

    Full Text Available Abstract Background Conversion of linoleic acid (LA and alpha-linolenic acid (ALA to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA- and alpha-linolenic acid ([13C]ALA-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D and delta-6 desaturase (D6D, peroxisome proliferator-activated receptor alpha (PPARα and sterol regulatory element binding protein 1c (SREBP-1c. Mitogen-activated protein kinase kinase 1 (MEK1 and mitogen-activated protein kinase kinase kinase 1 (MEKK1 were also examined. Results Maximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

  16. Incorporation of N-amidino-pyroglutamic acid into peptides using intramolecular cyclization of alpha-guanidinoglutaric acid.

    Science.gov (United States)

    Burov, Sergey; Moskalenko, Yulia; Dorosh, Marina; Shkarubskaya, Zoya; Panarin, Evgeny

    2009-11-01

    N-terminal modification of peptides by unnatural amino acids significantly affects their enzymatic stability, conformational properties and biological activity. Application of N-amidino-amino acids, positively charged under physiological conditions, can change peptide conformation and its affinity to the corresponding receptor. In this article, we describe synthesis of short peptides, containing a new building block-N-amidino-pyroglutamic acid. Although direct guanidinylation of pyroglutamic acid and oxidation of N-amidino-proline using RuO(4) did not produce positive results, N-amidino-Glp-Phe-OH was synthesized on Wang polymer by cyclization of alpha-guanidinoglutaric acid residue. In the course of synthesis, it was found that literature procedure of selective Boc deprotection using TMSOTf/TEA reagent is accompanied by concomitant side reaction of triethylamine alkylation by polymer linker fragment. It should be mentioned that independently from cyclization time and coupling agent (DIC or HCTU), the lactam formation was incomplete. Separation of the cyclic product from the linear precursor was achieved by HPLC in ammonium formate buffer at pH 6. HPLC analysis showed N-amidino-Glp-Phe-OH stability at acidic and physiological pH and fast ring opening in water solution at pH 9. The suggested method of N-amidino-Glp residue formation can be applied in the case of short peptide chains, whereas synthesis of longer ones will require fragment condensation approach.

  17. Effects of alpha-amylase and its inhibitors on acid production from cooked starch by oral streptococci.

    Science.gov (United States)

    Aizawa, S; Miyasawa-Hori, H; Nakajo, K; Washio, J; Mayanagi, H; Fukumoto, S; Takahashi, N

    2009-01-01

    This study evaluated acid production from cooked starch by Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and Streptococcus mitis, and the effects of alpha-amylase inhibitors (maltotriitol and acarbose) and xylitol on acid production. Streptococcal cell suspensions were anaerobically incubated with various carbohydrates that included cooked potato starch in the presence or absence of alpha-amylase. Subsequently, the fall in pH and the acid production rate at pH 7.0 were measured. In addition, the effects of adding alpha-amylase inhibitors and xylitol to the reaction mixture were evaluated. In the absence of alpha-amylase, both the fall in pH and the acid production rate from cooked starch were small. On the other hand, in the presence of alpha-amylase, the pH fell to 3.9-4.4 and the acid production rate was 0.61-0.92 micromol per optical density unit per min. These values were comparable to those for maltose. When using cooked starch, the fall in pH by S. sanguinis and S. mitis was similar to that by S. mutans and S. sobrinus. For all streptococci, alpha-amylase inhibitors caused a decrease in acid production from cooked starch, although xylitol only decreased acid production by S. mutans and S. sobrinus. These results suggest that cooked starch is potentially acidogenic in the presence of alpha-amylase, which occurs in the oral cavity. In terms of the acidogenic potential of cooked starch, S. sanguinis and S. mitis were comparable to S. mutans and S. sobrinus. Alpha-amylase inhibitors and xylitol might moderate this activity.

  18. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Directory of Open Access Journals (Sweden)

    Alicia I. Leikin-Frenkel

    2016-03-01

    Full Text Available The role of ω3 alpha linolenic acid (ALA in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA and eicosapentaenoic (EPA acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  19. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Science.gov (United States)

    Leikin-Frenkel, Alicia I.

    2016-01-01

    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring. PMID:27023621

  20. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Science.gov (United States)

    Leikin-Frenkel, Alicia I

    2016-03-23

    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  1. The application of glutamic acid alpha-decarboxylase for the valorization of glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Biase, De Daniela; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2009-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of nitrogen containing bulk chemicals, thereby decreasing the dependency on fossil fuels. On the pathway from glutamic acid to a range of molecules, the decar

  2. [Effect of dental alloys on salivary alkaline and acid phosphatase, alpha amylase K+, Na+, and Cl-].

    Science.gov (United States)

    Todorov, I; Saprjanova, M

    1977-04-01

    Comparative studied were performed in healthy subjects without metals in their oral cavities and in individuals having different metal alloys (gold, steel, amalgam) in their mouths and presenting with various complaints such as xerostomia, burning mucosa, etc. It was found that the contents of alkaline and acid phosphatases, alpha-amylase, K+, Na+ and Cl- in saliva increased significantly with the increase in total corrosion potential when non-precious metal alloys, especially different types of alloys, were present. Parallel to this, the frequency and the intensity of the complaints increased.

  3. Screening of Lactic Acid Bacteriafor Producing &alpha-Galactosidase from Chinese Traditional Fermented Foods

    Directory of Open Access Journals (Sweden)

    Xin-yong Du

    2012-12-01

    Full Text Available Twenty eight kinds of Chinese traditional fermented foods were collected to isolate Lactic Acid Bacteria (LAB with α-galactosidase activity, which could eliminated those α-Galactooligosaccharides (&alpha-GOS regarded as anti-nutritional factors widely existed in agricultural byproducts animal feeds. Three strains, including Lactobacillus salivarius XA1R (JX125455 and XH4B (JX125456 and Pediococcus acidilactici XS1B (JQ927329, could ferment well in soybean meal and other agricultural byproducts and had α-galactosidase activity 5.81-5.92 U/mL in soybean meal culture.

  4. Electrochemical and XPS studies of decylamides of {alpha}-amino acids adsorption on carbon steel in acidic environment

    Energy Technology Data Exchange (ETDEWEB)

    Olivares, O. [Programa de Ingenieria Molecular, Competencia de Quimica Aplicada, Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas No. 152, San Bartolo Atepehuacan, Mexico 07730, DF (Mexico); Instituto Politecnico Nacional-ESIQIE, Departamento de Ingenieria de Materiales y Metalurgia, Apdo. Postal 75-874, Mexico 07300, DF (Mexico); Likhanova, N.V. [Programa de Ingenieria Molecular, Competencia de Quimica Aplicada, Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas No. 152, San Bartolo Atepehuacan, Mexico 07730, DF (Mexico)]. E-mail: nvictoro@imp.mx; Gomez, B. [Programa de Ingenieria Molecular, Competencia de Quimica Aplicada, Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas No. 152, San Bartolo Atepehuacan, Mexico 07730, DF (Mexico); Navarrete, J. [Programa de Ingenieria Molecular, Competencia de Quimica Aplicada, Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas No. 152, San Bartolo Atepehuacan, Mexico 07730, DF (Mexico); Llanos-Serrano, M.E. [Programa de Ingenieria Molecular, Competencia de Quimica Aplicada, Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas No. 152, San Bartolo Atepehuacan, Mexico 07730, DF (Mexico); Arce, E. [Instituto Politecnico Nacional-ESIQIE, Departamento de Ingenieria de Materiales y Metalurgia, Apdo. Postal 75-874, Mexico 07300, DF (Mexico); Hallen, J.M. [Instituto Politecnico Nacional-ESIQIE, Departamento de Ingenieria de Materiales y Metalurgia, Apdo. Postal 75-874, Mexico 07300, DF (Mexico)

    2006-02-15

    Corrosion inhibition of steel in hydrochloric acid by decylamides of {alpha}-amino acids derivatives was studied using gravimetric and electrochemical techniques. Protection efficiencies of 90% were obtained with 100 ppm of tyrosine and glycine derivatives, while alanine and valine derivatives reached only 80%. The order of increasing inhibition efficiency was correlated with the modification of the molecular structure of inhibitors. Potentiodynamic polarization curves indicated that both the decylamide of tyrosine and glycine acted primarily as anodic type inhibitors, whereas the decylamide of alanine and valine were of the cathodic type. Thermodynamic parameters and Flory-Huggins adsorption isotherms described the experimental findings. The number of active sites, equilibrium constant, enthalpy and change of free energy were computed for all inhibitors studied. This information suggested that organic molecules were adsorbed and displaced water molecules from the steel surface. X-ray photoelectron spectroscopy confirmed that species of N, C and O interacted with steel to form a continuous protective film.

  5. 1, 4-alpha-Glucan phosphorylase from Klebsiella pneumoniae purification, subunit structure and amino acid composition.

    Science.gov (United States)

    Linder, D; Kurz, G; Bender, H; Wallenfels, K

    1976-11-01

    1. A 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae has been purified about 80-fold with an over-all yield greater than 35%. The purified enzyme has been shown to be homogeneous by gel electrophoresis at different pH-values, by isoelectric focusing, by dodecylsulfate electrophoresis and by ultracentrifugation. 2. The molecular weight of the native enzyme has been determined to be 180 000 by ultra-centrifugation studies, in good agreement with the value of 189 000 estimated by gel permeation chromatography. 3. The enzyme dissociates in the presence of 0.1% dodecylsulfate or 5 M guanidine hydrochloride into polypeptide chains. The molecular weight of these polypeptide chains has been found to be 88 000 by dodecylsulfate polyacrylamide gel electrophoresis and 99 000 by sedimentation equilibrium studies, indicating that the native enzyme is composed of two polypeptide chains. 4. The enzyme contains pyridoxalphosphate with a stoichiometry of two moles per 180 000 g protein, confirming that the 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae is a dimeric enzyme. 5. The amino acid composition of the enzyme has been determined, and its correspondence to that of 1,4-alpha-glucan phosphorylases from other sources is discussed. 6. The pI of the enzyme has been shown to be 5.3 and its pH-optimum to be about pH 5.9. The enzyme is stable in the range from pH 5.9 to 10.5.

  6. Chemical modification of an alpha 3-fucosyltransferase; definition of amino acid residues essential for enzyme activity.

    Science.gov (United States)

    Britten, C J; Bird, M I

    1997-02-11

    The biosynthesis of the carbohydrate antigen sialyl Lewis X (sLe(x)) is dependent on the activity of an alpha 3-fucosyltransferase (EC 2.4.1.152, GDP-fucose:Gal beta (1-4)GlcNAc-R alpha (1-3)fucosyltransferase). This enzyme catalyses the transfer of fucose from GDP-beta-fucose to the 3-OH of N-acetylglucosamine present in lactosamine acceptors. In this report, we have investigated the amino acids essential for the activity of a recombinant alpha 3-fucosyltransferase (FucT-VI) through chemical modification of the enzyme with group-selective reagents. FucT-VI activity was found to be particularly sensitive to the histidine-selective reagent diethylpyrocarbonate and the cysteine reagent N-ethylmaleimide, with IC50 values of less than 200 microM. Reagents selective for arginine and lysine had no effect on enzyme activity. The inclusion of GDP-beta-fucose during preincubation with NEM reduces the rate of inactivation whereas inclusion of an acceptor saccharide for the enzyme, Gal beta (1-4)GlcNAc, had no effect. No protective effect with either GDP-beta-fucose or Gal beta (1-4)GlcNAc was observed on treatment of the enzyme with diethylpyrocarbonate. These data suggest that in addition to an NEM-reactive cysteine in, or adjacent to, the substrate-binding site of the enzyme, FucT-VI possesses histidine residue(s) that are essential for enzyme activity.

  7. TRIM32 promotes retinoic acid receptor {alpha}-mediated differentiation in human promyelogenous leukemic cell line HL60

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Tomonobu [Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638 (Japan); Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo 060-8638 (Japan); Okumura, Fumihiko [Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638 (Japan); Iguchi, Akihiro; Ariga, Tadashi [Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo 060-8638 (Japan); Hatakeyama, Shigetsugu, E-mail: hatas@med.hokudai.ac.jp [Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer TRIM32 enhanced RAR{alpha}-mediated transcriptional activity even in the absence of RA. Black-Right-Pointing-Pointer TRIM32 stabilized RAR{alpha} in the human promyelogenous leukemic cell line HL60. Black-Right-Pointing-Pointer Overexpression of TRIM32 in HL60 cells induced granulocytic differentiation. Black-Right-Pointing-Pointer TRIM32 may function as a coactivator for RAR{alpha}-mediated transcription in APL cells. -- Abstract: Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor {alpha} (RAR{alpha}). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RAR{alpha} and enhances transcriptional activity of RAR{alpha} in mouse neuroblastoma cells and embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RAR{alpha}, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RAR{alpha}-mediated transcriptional activity even in the absence of RA and stabilizes RAR{alpha} in the human promyelogenous leukemic cell line HL60. Moreover, we found that overexpression of TRIM32 in HL60 cells suppresses cellular proliferation and induces granulocytic differentiation even in the absence of RA. These findings suggest that TRIM32 functions as one of the coactivators for RAR{alpha}-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL.

  8. The correlations among serum tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and sialic acids with peripheral lymphocytes in bovine tropical theileriosis.

    Science.gov (United States)

    Razavi, Seyed Mostafa; Nazifi, Saeed; Emadi, Mahboobeh; Rakhshandehroo, Ehsan

    2010-10-01

    The infection with protozoan parasite Theileria annulata induces changes triggering the activation and/or proliferation of the host lymphocytes. In order to find out the possible correlations among peripheral circulatory lymphocytes, cytokine activities and the level of sialic acids, 50 dairy Holstein cattle, naturally infected with T. annulata, were divided into 4 subgroups according to their parasitemia rates (5%). Also, ten non-infected cattle were sampled as control group. Blood samples were taken from jugular vein into acid citrate dextrose-containing tubes for measuring hematological parameters and B and T (CD(4) and CD(8)) cell populations and without anticoagulant for TNF-alpha, IFN-gamma and sialic acid concentrations. Remarkable decreases observed in red blood cells (RBCs), white blood cells (WBCs) and packed cell volume (PCV) in infected cattle compared to healthy ones (P < 0.05). Also, with increase in parasitemia rate, total lymphocytes and monocytes alleviated in the diseased groups. By contrast, total neutrohpils and the concentrations of TNF-alpha, IFN-gamma and total sialic acids were significantly elevated (P < 0.05) in infected animals. Accordingly, the circulatory populations of CD(4) and CD(8) T cells and B cells showed a substantial decrease, while a significant increase was observed in T (CD(4) and CD(8)) cells in cattle infected with <1% parasitemia rates. Decreased circulatory T cell population shows the ineffective responses of T cells to the stimulatory cytokines such as IFN-gamma or TNF-alpha. On the other hand, the elevation of cytokines (particularly IFN-gamma) and sialic acids have presumably an inhibitory role on circulatory B cell population in infected cattle. In addition, a high level of sialic acid concentration indicates the probable role of sialic acid to regulate the parasite-host cell adhesion during sporozoites invasion.

  9. The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPAR{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Danno, Hirosuke; Ishii, Kiyo-aki; Nakagawa, Yoshimi; Mikami, Motoki; Yamamoto, Takashi; Yabe, Sachiko; Furusawa, Mika; Kumadaki, Shin; Watanabe, Kazuhisa; Shimizu, Hidehisa; Matsuzaka, Takashi; Kobayashi, Kazuto; Takahashi, Akimitsu; Yatoh, Shigeru; Suzuki, Hiroaki; Yamada, Nobuhiro [Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575 (Japan); Shimano, Hitoshi, E-mail: hshimano@md.tsukuba.ac.jp [Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575 (Japan)

    2010-01-08

    To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fatty acids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPAR{alpha} agonist and repressed by PPAR{alpha} antagonist. Luciferase reporter gene assays indicated that the CREBH promoter activity was induced by fatty acids and co-expression of PPAR{alpha}. Deletion studies identified the PPRE for PPAR{alpha} activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPAR{alpha} directly binds to the PPRE. Activation of CREBH at fasting through fatty acids and PPAR{alpha} suggest that CREBH is involved in nutritional regulation.

  10. The radiolysis of CMPO: effects of acid, metal complexation and alpha vs. gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bruce J. Mincher; Stephen P. Mezyk; Gary S. Groenewold

    2016-05-01

    Abstract The group actinide/lanthanide complexing agent octylphenylcarbamoylmethyl phosphine oxide (CMPO) has been examined for its radiation stability by measuring the kinetics of its reactions with free radicals in both the aqueous and organic phases for the free and metal-complexed ligand, identifying its degradation products for both alpha and gamma irradiation, measuring the effects on solvent extraction performance, and measuring the G-values for its degradation under various conditions. This includes the G-values for CMPO in the absence of, and in contact with the acidic aqueous phase, where it is shown that the acidic aqueous phase provides radio-protection for this ligand. It was found that both solvent and metal complexation affect the kinetics of the reaction of the •NO3 radical, a product of HNO3 radiolysis, with CMPO. For example, CMPO complexed with lanthanides has a rate constant for this reaction an order of magnitude higher than for the free ligand, and the reaction for the free ligand in the organic phase is about three times faster than in the aqueous phase. In steady state radiolysis kinetics it was determined that HNO3, although not NO3- anion, provides radio-protection to CMPO, with the G-value for its degradation decreasing with increasing acidity, until it was almost completely suppressed by irradiation in contact with 5 M HNO3. The same degradation products were produced by irradiation with alpha and gamma-sources, except that the relative abundances of these products varied. For example, the product of C-C bond scission was produced only in low amounts for gamma-radiolysis, but it was an important product for samples irradiated with a He ion beam. These results are compared to the new data appearing in the literature on DGA radiolysis, since CMPO and the DGAs both contain the amide functional group.

  11. Saponification of esters of chiral alpha-amino acids anchored through their amine function on solid support.

    Science.gov (United States)

    Cantel, Sonia; Desgranges, Stéphane; Martinez, Jean; Fehrentz, Jean-Alain

    2004-06-01

    Anchoring an alpha-amino acid residue by its amine function onto a solid support is an alternative to develop chemistry on its carboxylic function. This strategy can involve the use of amino-acid esters as precursors of the carboxylic function. A complete study on the Wang-resin was performed to determine the non racemizing saponification conditions of anchored alpha-amino esters. The use of LiOH, NaOH, NaOSi(Me)3, various solvents and temperatures were tested for this reaction. After saponification and cleavage from the support, samples were examined through their Marfey's derivatives by reversed phase HPLC to evaluate the percentage of racemization.

  12. Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids.

    Science.gov (United States)

    Gibson, R A; Neumann, M A; Lien, E L; Boyd, K A; Tu, W C

    2013-01-01

    The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07-17.1 en%) and ALA (0.02-12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1-3 en% ALA and 1-2 en% LA but was suppressed to basal levels (∼2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).

  13. Proton exchange nanocomposite membranes based on 3-glycidoxypropyltrimethoxysilane, silicotungstic acid and {alpha}-zirconium phosphate hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yong-il; Nagai, Masayuki [Advanced Research Center for Energy and Environment, Musashi Institute of Technology, 1-28-1 Tamazutsumi, Tokyo 158-8557 Setagaya (Japan)

    2001-12-01

    Novel fast proton-conducting GPTS-STA-SiO{sub 2} and GPTS-STA-ZrP composites were successfully fabricated. The polymer matrix obtained through hydrolysis and condensation reaction of 3-glycidoxypropyltrimethoxysilane (GPTS) showed apparent proton conduction at high relative humidity with conductivity from 1.0x10{sup -7} to 3.6x10{sup -6} S/cm, although no proton donor was incorporated. The proton conductivities of the fabricated composites were high, and increased up to 1.9x10{sup -2} S/cm by addition of silicotungstic acid (STA). By incorporating {alpha}-zirconium phosphate (ZrP) into the GPTS-STA polymer matrix, the composite showed increased conductivity at low temperature (80C), indicating weak dependence on humidity by molecular water in ZrP. The high proton conductivity of the composites is due to the proton conducting path through the GPTS-derived 'pseudo-polyethylene oxide (pseudo-PEO)' networks, which also contains a trapped solid acid (silicotungstic acid) as a proton donor.

  14. Semiconductor effect on the selective photocatalytic reaction of. alpha. -hydroxycarboxylic acids

    Energy Technology Data Exchange (ETDEWEB)

    Harada, H.; Ueda, T. (Meisei Univ., Tokyo (Japan)); Sakata, T. (Institute for Molecular Science, Okazaki (Japan))

    1989-02-23

    Photocatalytic and photoelectrochemical reactions of {alpha}-hydroxycarboxylic acids were compared for various types of semiconductor electrode (TiO{sub 2}, CdS, SrTiO{sub 3}, and ZnO) and suspension of particulate semiconductor (TiO{sub 2}, CdS, MoS{sub 2}, and ZnS). These reactions were found to depend strongly on the type of semiconductor studied. In the cases of Pt/CdS and ZnS photocatalysts, the hydroxy group of the acids was oxidized selectively into the corresponding keto acids, whereas in the cases of Pt/TiO{sub 2}, decarboxylation took place in addition to dehydrogenation. The same dependence was observed in the photoelectrochemical reactions with semiconductor single-crystal electrodes. For the TiO{sub 2} electrode, the reaction depends strongly on pH, whereas it does not for CdS. The results of pH effects, electrochemical reaction with various metal electrodes, and Fenton reaction in a homogeneous solution suggest the importance of adsorption of the reactants on the semiconductor and metal surfaces for the selective reaction.

  15. Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Pedersen, SB;

    2006-01-01

    Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined whether plasma TNF-alpha is associated with the degree by which insulin suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and net lipid oxidation (LIPOX) rate in HIV-infected patients...

  16. Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren;

    2007-01-01

    Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown....... In the present study, we examined the effect of Snca gene ablation on brain 22:6n-3 metabolism. We determined 22:6n-3 uptake and incorporation into brain phospholipids by infusing awake, wild-type and Snca-/- mice with [1-14C]22:6n-3 using steady-state kinetic modeling. In addition, because Snca modulates 20:4n...

  17. Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

    Directory of Open Access Journals (Sweden)

    P. Roncada

    2010-04-01

    Full Text Available Alpha1-acid glycoprotein (AGP is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations. In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far.

  18. Evolution of human alpha 1-acid glycoprotein genes and surrounding Alu repeats.

    Science.gov (United States)

    Merritt, C M; Easteal, S; Board, P G

    1990-04-01

    There is a mosaic pattern of variation between the two tandemly arranged human alpha 1-acid glycoprotein genes. Both the synonymous and the nonsynonymous sites of exons 3 and 4 are more divergent than the rest of the gene, suggesting that they have had a different evolutionary history. Comparisons of the two gene sequences with rat AGP indicate that exons 3 and 4 of AGP2 have been evolving without functional constraint since their divergence from AGP1. It is proposed that the conserved region of the gene has been homogenized recently by gene conversion with the homologous regions of AGP1. The Alu sequences surrounding the genes appear to have been involved in both the gene duplication and the gene conversion events.

  19. Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis

    DEFF Research Database (Denmark)

    Andersen, U O; Kirkeby, S; Bøg-Hansen, T C

    1997-01-01

    Three glycoforms of alpha 1-acid glycoprotein (AGP) were biotinylated to examine their binding in mouse testis by light microscopy. The transition from one stage to another in the spermatogenic cycle is marked with an appearance of a receptor for the Concanavalin A (Con A) non-reactive glycoform...... AGP-A in the cytoplasm of spermatocytes, young spermatids and Sertoli cells. This receptor disappears in the late stages of the spermatids. The Con-A intermediately reactive and the Con-A reactive glycoforms, AGP-B and AGP-C, showed weak reaction in the cytoplasm of spermatocytes, spermatids....... AGP-A was inhibited by testosterone, oestradiol and progesterone, while AGP-B and AGP-C were inhibited by mannose, GlcNAc, cortisone, aldosterone, oestradiol and progesterone. The receptors and the corresponding AGP glycoforms may be adhesion molecules between Sertoli cells and the spermatogenic cells...

  20. Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning

    OpenAIRE

    2015-01-01

    Background Alpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning. Methods 3 month...

  1. Relation between the secondary structure of carbohydrate residues of alpha1-acid glycoprotein (orosomucoid) and the fluorescence of the protein.

    Science.gov (United States)

    Albani, Jihad R

    2003-05-01

    We studied in this work the relation that exists between the secondary structure of the glycans of alpha(1)-acid glycoprotein and the fluorescence of the Trp residues of the protein. We calculated for that the efficiency of quenching and the radiative and non-radiative constants. Our results indicate that the glycans display a spatial structure that is modified upon asialylation. The asialylated conformation is closer to the protein matrix than the sialylated form, inducing by that a decrease in the fluorescence parameters of the Trp residues. In fact, the mean quantum yield of Trp residues in sialylated and asialylated alpha(1)-acid glycoprotein are 0.0645 and 0.0385, respectively. Analysis of the fluorescence emission of alpha(1)-acid glycoprotein as the result of two contributions (surface and hydrophobic domains) indicates that quantum yields of both classes of Trp residues are lower when the protein is in the asialylated form. Also, the mean fluorescence lifetime of Trp residues decreases from 2.285 ns in the sialylated protein to 1.948 ns in the asialylated one. The radiative rate constant k(r) of the Trp residues in the sialylated alpha(1)-acid glycoprotein is higher than that in the asialylated protein. Thus, the carbohydrate residues are closer to the Trp residues in the absence of sialic acid. The modification of the spatial conformation of the glycans upon asialylation is confirmed by the decrease of the fluorescence lifetimes of Calcofluor, a fluorophore that binds to the carbohydrate residues. Finally, thermal intensity quenching of Calcofluor bound to alpha(1)-acid glycoprotein shows that the carbohydrate residues have slower residual motions in the absence of sialic acid residues.

  2. Alpha-Linolenic Acid: An Omega-3 Fatty Acid with Neuroprotective Properties—Ready for Use in the Stroke Clinic?

    Directory of Open Access Journals (Sweden)

    Nicolas Blondeau

    2015-01-01

    Full Text Available Alpha-linolenic acid (ALA is plant-based essential omega-3 polyunsaturated fatty acids that must be obtained through the diet. This could explain in part why the severe deficiency in omega-3 intake pointed by numerous epidemiologic studies may increase the brain’s vulnerability representing an important risk factor in the development and/or deterioration of certain cardio- and neuropathologies. The roles of ALA in neurological disorders remain unclear, especially in stroke that is a leading cause of death. We and others have identified ALA as a potential nutraceutical to protect the brain from stroke, characterized by its pleiotropic effects in neuroprotection, vasodilation of brain arteries, and neuroplasticity. This review highlights how chronic administration of ALA protects against rodent models of hypoxic-ischemic injury and exerts an anti-depressant-like activity, effects that likely involve multiple mechanisms in brain, and may be applied in stroke prevention. One major effect may be through an increase in mature brain-derived neurotrophic factor (BDNF, a widely expressed protein in brain that plays critical roles in neuronal maintenance, and learning and memory. Understanding the precise roles of ALA in neurological disorders will provide the underpinnings for the development of new therapies for patients and families who could be devastated by these disorders.

  3. The content and distribution of troponin I, troponin T, myoglobin, and alpha-hydroxybutyric acid dehydrogenase in the human heart

    NARCIS (Netherlands)

    Swaanenburg, JCJM; Visser-VanBrummen, PJ; DeJongste, MJL; Tiebosch, ATHM

    2001-01-01

    We studied the content and distribution of heart-specific markers troponin I and troponin T in relation to conventional non-heart specific myoglobin and alpha-hydroxybutyric acid dehydrogenase (HBD) in the hearts of 34 patients who died of various causes. Tissue was obtained from the right and left

  4. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II

    NARCIS (Netherlands)

    A.G.A. Bijvoet (Agnes); A.J.J. Reuser (Arnold); H. van Hirtum (Hans); M.A. Kroos (Marian); E.H. van de Kamp; O. Schoneveld; P. Visser (Pim); J.P. Brakenhoff (Just); M. Weggeman; E.J.J.M. van Corven (Emiel); A.T. van der Ploeg (Ans)

    1999-01-01

    textabstractPompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and s

  5. Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production

    NARCIS (Netherlands)

    Mathioudakis, D.; Engel, J.; Welters, I.D.; Dehne, M.G.; Matejec, R.; Harbach, H.; Henrich, M.; Schwandner, T.; Fuchs, M.; Weismuller, K.; Scheffer, G.J.; Muhling, J.

    2011-01-01

    For the first time the immunonutritional role of pyruvate on neutrophils (PMN), free alpha-keto and amino acid profiles, important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] as well as released myeloperoxidase (MPO) acitivity has been investiga

  6. Characterization of genomic rearrangements of the alpha1-acid glycoprotein/orosomucoid gene in Ghanaians.

    Science.gov (United States)

    Yuasa, I; Nakamura, H; Henke, L; Henke, J; Nakagawa, M; Irizawa, Y; Umetsu, K

    2001-01-01

    In this study, the structure of the alpha1-acid glycoprotein (AGP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORMI*S and ORMI*S2(C), had the AGP2 gene-specific sequence at one and three regions, respectively, in exon 5 to intron 5. The variant allele originating from ORMi*S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected in ORM1 F2, a form that is common in Europeans. (2) The AGP2 gene of the child, inherited from the father, was duplicated, as revealed by long-range polymerase chain reaction. (3) Three new mutations were observed in two exons of the AGP2 genes of the mother and child. All of these novel genomic rearrangements, which were not observed in Japanese subjects, may have arisen through point mutation, gene conversion, and unequal crossover events. It is likely that the rearrangement of the AGP gene has often occurred in Africans.

  7. Cloning the mouse homologue of the human lysosomal acid {alpha}-glucosidase gene

    Energy Technology Data Exchange (ETDEWEB)

    Ding, J.H.; Yang, B.Z.; Liu, H.M. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1994-09-01

    Pompe disease (GSD II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid {alpha}-glucosidase (GAA). In an attempt to create a mouse model for Pompe disease, we isolated and characterized the gene encoding the mouse homologue of the human GAA. Twenty clones that extend from exon 2 to the poly(A) tail were isolated from a mouse liver cDNA library, but the remainder of the mRNA proved difficult to obtain by conventional cDNA library screening. Sequences spanning exons 1-2 were cloned by RACE from mouse liver RNA. The full-length liver GAA cDNA contains 3365 nucleotides with a coding region of 2859 nucleotides and a 394 base pair 3{prime}-nontranslated region. The deduced amino acid sequence of the mouse GAA shows 84% identity to the human GAA. Southern blot analysis demonstrated that the mouse GAA was encoded by a single copy gene. Then six bacteriophages containing DNA from the GAA gene were isolated by screening 10{sup 6} phage plaques of a mouse 129 genomic library using a mouse GAA cDNA as a probe. From one of these bacteriophages, an 11-kilobase EcoRI fragment containing exons 3 to 15 was subcloned and sequenced. Work is in progress using this genomic clone to disrupt the GAA gene in murine embryonic stem cells in order to create GSD II mice.

  8. α-硫辛酸和乙酰左旋肉碱改善炎症细胞因子介导胰岛细胞功能障碍的作用%Effects of α-Lipoic Acid and Acetyl-L-Carnitine on Cytokines-Induced Islet Cell Dysfunction

    Institute of Scientific and Technical Information of China (English)

    张召锋; 顾娇娇; 鲍雷; 蔡夏夏; 李勇

    2014-01-01

    目的:探讨α-硫辛酸(α-lipoic acid,LA)和乙酰左旋肉碱(acetyl-L-camitine,ALC)改善炎症细胞因子介导胰岛细胞功能障碍的效果并探讨机制.方法:大鼠胰岛素瘤RIN-m5f细胞用肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β (interleukin-1β, IL-1β)和γ-干扰素(interferon-γ,IFN-γ)联合作用(TⅡ)48 h造成损伤模型.LA和ALC干预48 h后噻唑蓝法检测胰岛细胞的活力情况,荧光细胞技术法检测细胞的形态学,流式细胞仪检测细胞活性氧(reactive oxygen species,ROS)表达水平,放射免疫法检测胰岛素分泌情况,Western blotting检测细胞凋亡相关和胰岛素分泌相关蛋白表达情况.结果:TⅡ作用48 h可使RIN-m5f细胞活力明显下降,凋亡增加;并降低基础状态下和高糖刺激状态下胰岛素分泌水平;增加ROS水平,增加一氧化氮合酶(nitric oxidesynthase,NOS)活性,增加一氧化氮(nitrogen monoxide,NO)水平,促进NF-κB向细胞核转位;TⅡ还可增加RIN-m5f细胞内促凋亡蛋白Bax、Caspase-3表达,抑制抗凋亡蛋白I-κB、Bcl-2表达,增加线粒体细胞色素c释放.而LA、ALC可改善TⅡ诱导的RIN-m5f细胞凋亡,提高基础状态和高糖刺激状态下胰岛素分泌水平;抑制NF-κB向细胞核转位、降低细胞NO水平;降低Bax、Caspase-3表达,增加抗凋亡蛋白I-κB、Bcl-2表达,抑制线粒体细胞色素c释放;LA与ALC联合作用效果强于单独作用.结论:炎症细胞因子作用48 h可通过ROS-cytochrome c-NF-κB-NOS-NO通路最终引起胰岛β细胞的凋亡,进而影响胰岛素分泌;LA和ALC联用可抑制炎症细胞因子诱导的胰岛细胞凋亡,促进胰岛素分泌.

  9. Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids.

    Science.gov (United States)

    Handschin, Christoph; Gnerre, Carmela; Fraser, David J; Martinez-Jimenez, Celia; Jover, Ramiro; Meyer, Urs A

    2005-02-01

    The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver receptor homolog-1, mRNA expression of these nuclear receptors is unchanged by xenobiotics. Instead, drugs repress chicken hepatic nuclear factor 4alpha (HNF4alpha) transcript levels concomitant with a reduction in CYP7A1 expression. Importantly, no reduction of HNF4alpha levels is found in mouse liver in vivo and in human primary hepatocyte cultures, respectively. Thus, besides the importance of HNF4alpha in CYP7A1 regulation in all species, birds and mammals use different signaling pathways to adjust CYP7A1 levels after exposure to xenobiotics.

  10. Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue.

    Science.gov (United States)

    Polak, Jan; Moro, Cédric; Bessière, David; Hejnova, Jindra; Marquès, Marie A; Bajzova, Magda; Lafontan, Max; Crampes, Francois; Berlan, Michel; Stich, Vladimir

    2007-10-01

    The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

  11. Nutritional Effect of Alpha-Linolenic Acid on Honey Bee Colony Development (Apis Mellifera L.

    Directory of Open Access Journals (Sweden)

    Ma Lanting

    2015-12-01

    Full Text Available Alpha-linolenic acid (ALA, which is an n-3 polyunsaturated fatty acid (PUFA, influences honey bee feed intake and longevity. The objective of this study was to research the effect of six dietary ALA levels on the growth and development of Apis mellifera ligustica colonies. In the early spring, a total of 36 honey bee colonies of equal size and queen quality were randomly allocated into 6 groups. The six groups of honey bees were fed a basal diet with supplementation of ALA levels at 0 (group A, 2 (group B, 4 (group C, 6 (group D, 8 (group E, and 10% (group F. In this study, there were significant effects of pollen substitute ALA levels on the feeding amounts of the bee colony, colony population, sealed brood amount, and weight of newly emerged workers (P<0.05. The workers’ midgut Lipase (LPS activity of group C was significantly lower than that of the other groups (P<0.01. The worker bees in groups B, C, and D had significantly longer lifespans than those in the other groups (P<0.05. However, when the diets had ALA concentrations of more than 6%, the mortality of the honey bees increased (P<0.01. These results indicate that ALA levels of 2 ~ 4% of the pollen substitute were optimal for maintaining the highest reproductive performance and the digestion and absorption of fatty acids in honey bees during the period of spring multiplication. Additionally, ALA levels of 2 ~ 6% of the pollen substitute, improved worker bee longevity.

  12. Control of. cap alpha. -amylase mRNA accumulation by gibberellic acid and calcium in barley aleurone layers

    Energy Technology Data Exchange (ETDEWEB)

    Deikman, J.; Jones, R.L.

    1985-01-01

    Pulse-labeling of barley (Hordeum vulgare L. cv Himalaya) aleurone layers incubated for 13 hours in 2.5 micromolar gibberellic acid (GA/sub 3/) with or without 5 millimolar CaCl/sub 2/ shows that ..cap alpha..-amylase isozymes 3 and 4 are not synthesized in vivo in the absence of Ca/sup 2 +/. No difference was observed in ..cap alpha..-amylase mRNA levels between layers incubated for 12 hours in 2.5 micromolar GA/sub 3/ with 5 millimolar CaCl/sub 2/ and layers incubated in GA/sub 3/ alone. RNA isolated from layers incubated for 12 hours in GA/sub 3/ with and without CA/sup 2 +/. A cDNA clone for ..cap alpha..-amylase was isolated and used to measure ..cap alpha..-amylase mRNA levels in aleurone layers incubated in the presence and absence of Ca/sup 2 +/ was translated in vitro and was found to produce the same complement of translation products regardless of the presence of Ca/sup 2 +/ in the incubation medium. Immunoprecipitation of translation products showed that the RNA for ..cap alpha..-amylase synthesized in Ca/sup 2 +/-deprived aleurone layers was translatable. Ca/sup 2 +/ is required for the synthesis of ..cap alpha..-amylase isozymes 3 and 4 at a step after mRNA accumulation and processing.

  13. Diacylglycerol pyrophosphate inhibits the alpha-amylase secretion stimulated by gibberellic acid in barley aleurone.

    Science.gov (United States)

    Racagni, Graciela; Villasuso, Ana L; Pasquaré, Susana J; Giusto, Norma M; Machado, Estela

    2008-11-01

    ABA plays an important regulatory role in seed germination because it inhibits the response to GA in aleurone, a secretory tissue surrounding the endosperm. Phosphatidic acid (PA) is a well-known intermediary in ABA signaling, but the role of diacylglycerol pyrophosphate (DGPP) in germination processes is not clearly established. In this study, we show that PA produced by phospholipase D (E.C. 3.1.4.4) during the antagonist effect of ABA in GA signaling is rapidly phosphorylated by phosphatidate kinase (PAK) to DGPP. This is a crucial fact for aleurone function because exogenously added dioleoyl-DGPP inhibits secretion of alpha-amylase (E.C. 3.2.1.1). Aleurone treatment with ABA and 1-butanol results in normal secretory activity, and this effect is reversed by addition of dioleoyl-DGPP. We also found that ABA decreased the activity of an Mg2+-independent, N-ethylmaleimide-insensitive form of phosphatidate phosphohydrolase (PAP2) (E.C. 3.1.3.4), leading to reduction of PA dephosphorylation and increased PAK activity. Sequence analysis using Arabidopsis thaliana lipid phosphate phosphatase (LPP) sequences as queries identified two putative molecular homologues, termed HvLPP1 and HvLPP2, encoding putative Lpps with the presence of well-conserved structural Lpp domains. Our results are consistent with a role of DGPP as a regulator of ABA antagonist effect in GA signaling and provide evidence about regulation of PA level by a PAP2 during ABA response in aleurone.

  14. The conjugated linoleic acid isomer trans-9,trans-11 is a dietary occurring agonist of liver X receptor {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Josef; Liebisch, Gerhard [Institute of Clinical Chemistry, University of Regensburg (Germany); Patsch, Wolfgang [Department of Laboratory Medicine, Hospital of Salzburg (Austria); Schmitz, Gerd, E-mail: gerd.schmitz@klinik.uni-regensburg.de [Institute of Clinical Chemistry, University of Regensburg (Germany)

    2009-10-30

    Conjugated linoleic acid (CLA) isomers are dietary fatty acids that modulate gene expression in many cell types. We have previously reported that specifically trans-9,trans-11 (t9,t11)-CLA induces expression of genes involved in lipid metabolism of human macrophages. To elucidate the molecular mechanism underlying this transcriptional activation, we asked whether t9,t11-CLA affects activity of liver X receptor (LXR) {alpha}, a major regulator of macrophage lipid metabolism. Here we show that t9,t11-CLA is a regulator of LXR{alpha}. We further demonstrate that the CLA isomer induces expression of direct LXR{alpha} target genes in human primary macrophages. Knockdown of LXR{alpha} with RNA interference in THP-1 cells inhibited t9,t11-CLA mediated activation of LXR{alpha} including its target genes. To evaluate the effective concentration range of t9,t11-CLA, human primary macrophages were treated with various doses of CLA and well known natural and synthetic LXR agonists and mRNA expression of ABCA1 and ABCG1 was analyzed. Incubation of human macrophages with 10 {mu}M t9,t11-CLA led to a significant modulation of ABCA1 and ABCG1 transcription and caused enhanced cholesterol efflux to high density lipoproteins and apolipoprotein AI. In summary, these data show that t9,t11-CLA is an agonist of LXR{alpha} in human macrophages and that its effects on macrophage lipid metabolism can be attributed to transcriptional regulations associated with this nuclear receptor.

  15. Comparison of starch hydrolysis activity and thermal stability of two Bacillus licheniformis alpha-amylases and insights into engineering alpha-amylase variants active under acidic conditions.

    Science.gov (United States)

    Lee, Seunjae; Oneda, Hiroshi; Minoda, Masashi; Tanaka, Akiyoshi; Inouye, Kuniyo

    2006-06-01

    Bacillus licheniformis alpha-amylase (BLA) is widely used in various procedures of starch degradation in the food industry, and a BLA species with improved activity at higher temperature and under acidic conditions is desirable. Two BLA species, designated as PA and MA, have been isolated from the wild-type B. licheniformis strain and a mutant strain, respectively. In this study, their starch-hydrolysis activity and thermal stability were examined. MA showed higher activity than PA, especially at acidic pH (pH 5.0-5.5), and even after 1 h of treatment at 90 degrees C. MA was active in the range of pH 4.0-8.0, which is much wider than that (pH 4.5-7.5) of PA. It was shown that the proton dissociation constants on the acidic and alkaline sides (pKa1 and pKa2) were shifted to more acidic and basic values, respectively, by the mutation of PA to MA. The activation energy and thermodynamic parameters for their thermal inactivation indicate that MA is more thermally stable and catalytically active than PA, suggesting that MA could be useful for glucose-production process coupled with reactions catalyzed by beta-amylase.

  16. No need to be HAMLET or BAMLET to interact with histones: binding of monomeric alpha-lactalbumin to histones and basic poly-amino acids.

    Science.gov (United States)

    Permyakov, Serge E; Pershikova, Irina V; Khokhlova, Tatyana I; Uversky, Vladimir N; Permyakov, Eugene A

    2004-05-18

    The ability of a specific complex of human alpha-lactalbumin with oleic acid (HAMLET) to induce cell death with selectivity for tumor and undifferentiated cells was shown recently to be mediated by interaction of HAMLET with histone proteins irreversibly disrupting chromatin structure [Duringer, C., et al. (2003) J. Biol. Chem. 278, 42131-42135]. Here we show that monomeric alpha-lactalbumin (alpha-LA) in the absence of fatty acids is also able to bind efficiently to the primary target of HAMLET, histone HIII, regardless of Ca(2+) content. Thus, the modification of alpha-LA by oleic acid is not required for binding to histones. We suggest that interaction of negatively charged alpha-LA with the basic histone stabilizes apo-alpha-LA and destabilizes the Ca(2+)-bound protein due to compensation for excess negative charge of alpha-LA's Ca(2+)-binding loop by positively charged residues of the histone. Spectrofluorimetric curves of titration of alpha-LA by histone H3 were well approximated by a scheme of cooperative binding of four alpha-LA molecules per molecule of histone, with an equilibrium dissociation constant of 1.0 microM. Such a stoichiometry of binding implies that the binding process is not site-specific with respect to histone and likely is driven by just electrostatic interactions. Co-incubation of positively charged poly-amino acids (poly-Lys and poly-Arg) with alpha-LA resulted in effects which were similar to those caused by histone HIII, confirming the electrostatic nature of the alpha-LA-histone interaction. In all cases that were studied, the binding was accompanied by aggregation. The data indicate that alpha-lactalbumin can be used as a basis for the design of antitumor agents, acting through disorganization of chromatin structure due to interaction between alpha-LA and histone proteins.

  17. Who is Mr. HAMLET? Interaction of human alpha-lactalbumin with monomeric oleic acid.

    Science.gov (United States)

    Knyazeva, Ekaterina L; Grishchenko, Valery M; Fadeev, Roman S; Akatov, Vladimir S; Permyakov, Sergei E; Permyakov, Eugene A

    2008-12-09

    A specific state of the human milk Ca(2+) binding protein alpha-lactalbumin (hLA) complexed with oleic acid (OA) prepared using an OA-pretreated ion-exchange column (HAMLET) triggers several cell death pathways in various tumor cells. The possibility of preparing a hLA-OA complex with structural and cytotoxic properties similar to those of the HAMLET but under solution conditions has been explored. The complex was formed by titration of hLA by OA at pH 8.3 up to OA critical micelle concentration. We have shown that complex formation strongly depends on calcium, ionic strength, and temperature; the optimal conditions were established. The spectrofluorimetrically estimated number of OA molecules irreversibly bound per hLA molecule (after dialysis of the OA-loaded preparation against water followed by lyophilization) depends upon temperature: 2.9 at 17 degrees C (native apo-hLA; resulting complex referred to as LA-OA-17 state) and 9 at 45 degrees C (thermally unfolded apo-hLA; LA-OA-45). Intrinsic tryptophan fluorescence measurements revealed substantially decreased thermal stability of Ca(2+)-free forms of HAMLET, LA-OA-45, and OA-saturated protein. The irreversibly bound OA does not affect the Ca(2+) association constant of the protein. Phase plot analysis of fluorimetric and CD data indicates that the OA binding process involves several hLA intermediates. The effective pseudoequilibrium OA association constants for Ca(2+)-free hLA were estimated. The far-UV CD spectra of Ca(2+)-free hLA show that all OA-bound forms of the protein are characterized by elevated content of alpha-helical structure. The various hLA-OA complexes possess similar cytotoxic activities against human epidermoid larynx carcinoma cells. Overall, the LA-OA-45 complex possesses physicochemical, structural, and cytotoxic properties closely resembling those of HAMLET. The fact that the HAMLET-like complex can be formed in aqueous solution makes the process of its preparation more transparent and

  18. alpha,omega-Dicarboxylic acid accumulation by acyl-CoA oxidase deficient mutants of Yarrowia lipolytica.

    Science.gov (United States)

    Smit, Martha S; Mokgoro, Masego M; Setati, Evodia; Nicaud, Jean-Marc

    2005-06-01

    alpha,omega-Dicarboxylic acid accumulation from alkanes and alkane degradation intermediates was investigated using Yarrowia lipolytica wild type strain W29 as well as a double, a triple and a quadruple POX-deleted strains. Six genes, POX1 through POX6, encode six acyl-CoA oxidase isozymes in Y. lipolytica. All the strains accumulated dodecanedioic acid (5-20 mg ml(-1)) from the diterminal functionalised 1,12-dodecane diol and 12-hydroxdodecanoic acid. The quadruple-deleted strain was the only strain that was able to accumulate dioic acids from C16 alkanol and monocarboxylic acid as well as from C12, C14 and C16 alkanes (maximum 8 mg ml(-1) from dodecane).

  19. Cytotoxic lipidic {alpha}-amino acids from the zoanthid Protopalythoa variabilis from the Northeastern coast of Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Wilke, Diego Veras; Jimenez, Paula Christine; Pessoa, Claudia; Moraes, Manoel Odorico de; Costa-Lotufo, Leticia Veras [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Faculdade de Medicina. Dept. de Fisiologia e Farmacologia], e-mail: lvcosta@secrel.com.br, e-mail: lvcosta@ufc.br; Araujo, Renata Mendonca; Silva, Wildson Max Barbosa da; Silveira, Edilberto Rocha; Pessoa, Otilia Deusdenia Loiola; Braz-Filho, Raimundo [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica; Lopes, Norberto Peporine [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Ciencias Farmaceuticas. Dept. de Fisica e Quimica

    2009-07-01

    Two lipidic {alpha}-amino acids 1a and 1b were isolated from the zoanthid Protopalythoa variabilis using a bioguided fractionation for cytotoxic activity. The structures of the metabolites were determined by spectroscopic methods, including NMR (nuclear magnetic resonance) {sup 1}H and {sup 13}C, IR infrared) and high resolution mass spectrometry (positive mode). The cytotoxic activity of the crude extract, as well as of the mixture of 1a and 1b were measured in vitro using the MTT assay for four human tumor cell lines. This finding has important biological and chemical implications for this type of compound. This is the first report of lipidic {alpha}-amino acids from natural sources, as well as of their cytotoxic activity. (author)

  20. High-performance liquid chromatographic separation of carminic acid, alpha- and beta-bixin, and alpha- and beta-norbixin, and the determination of carminic acid in foods.

    Science.gov (United States)

    Lancaster, F E; Lawrence, J F

    1996-05-03

    During a study of natural food colours, a simple and reliable high-performance liquid chromatography system was developed for use with cochineal and annato. An isocratic mobile phase, consisting of methanol and 6% aqueous acetic acid, resolved bixin and norbixin, while a gradient system was used to separate carminic acid and the annato compounds. The carminic acid contents of cochineal extract, carmine and carmine hydrosoluble were determined using an isocratic mobile phase (40:60, v/v). The detection limit for carminic acid in the various products was approximately 100 ng/g. Carminic acid was determined quantitatively in fruit beverages, yogurt and candies. It was demonstrated that, because of decomposition, carminic acid was not suitable for use in candies when manufacturing temperatures above 100 degrees C were required. Most membrane filters are not suitable for use with cochineal solutions, but a cellulose membrane filter did not adsorb carminic acid and was used successfully to remove impurities from water-based cochineal products and food extracts containing carminic acid.

  1. NMR study of the preparation of 6 {alpha}, 7 {beta}-dihydroxyvouacapan-17 beta-oic acid mannich base derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Flavio Jose Leite dos; Pilo-Veloso, Dorila [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Inst. de Ciencias Exatas. Dept. Quimica]. E-mail: dorila@zeus.qui.ufmg.br; Ferreira-Alves, Dalton L. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Inst. de Ciencias Biologicas. Dept. de Farmacologia

    2007-07-01

    This work presents four new Mannich base compounds obtained by the Mannich reaction of a {delta}-keto-lactone derivative of 6{alpha}, 7{beta}-dihydroxyvouacapan- 17{beta}-oic acid, a furano diterpene isolated from the hexane extract of Pterodon polygalaeflorus Benth fruits, which shows anti-inflammatory and analgesic activities. The use of 1D and 2D NMR (COSY, DEPT-135, HMBC, HMQC) spectroscopy made it possible to characterize the new compounds. (author)

  2. The bioactive compounds alpha-chaconine and gallic acid in potato extracts decrease survival and induce apoptosis in LNCaP and PC3 prostate cancer cells.

    Science.gov (United States)

    Reddivari, Lavanya; Vanamala, Jairam; Safe, Stephen H; Miller, J Creighton

    2010-01-01

    We recently reported that colored potato extracts and an anthocyanin rich fraction suppressed lymph-node carcinoma of the prostate (LNCaP) and prostate cancer-3 (PC-3) prostate cancer cell proliferation and induced apoptosis via caspase-dependent and caspase-independent pathways. Chlorogenic acid, caffeic acid, gallic acid, catechin, malvidin, and glycoalkaloids (alpha-chaconine and solanine) have now been identified as the major bioactive components of potato, and their effects on LNCaP and PC-3 cell proliferation and apoptosis have been investigated. alpha-chaconine (5 microg/ml) and gallic acid (15 microg/ml) exhibited potent antiproliferative properties and increased cyclin-dependent kinase inhibitor p27 levels in both cell lines. Both alpha-chaconine and gallic acid induced poly [adenosine diphosphate (ADP)] ribose polymerase cleavage and caspase-dependent apoptosis in LNCaP cells; however, caspase-independent apoptosis through nuclear translocation of endonuclease G was observed in both LNCaP and PC-3 cells. alpha-chaconine and gallic acid activated c-Jun N-terminal protein kinase (JNK), and this response played a major role in induction of caspase-dependent apoptosis in LNCaP cells; whereas modulation of JNK and mitogen-activated protein kinase did not affect alpha-chaconine- and gallic acid-induced caspase-independent apoptosis. These results suggest that apoptosis induced by whole potato extracts in prostate cancer cell lines may be in part due to alpha-chaconine and gallic acid.

  3. Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.

    Science.gov (United States)

    Cardona-Gómez, Gloria Patricia; Arango-Davila, Cesar; Gallego-Gómez, Juan Carlos; Barrera-Ocampo, Alvaro; Pimienta, Hernan; Garcia-Segura, Luis Miguel

    2006-08-21

    During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.

  4. Influence of ascorbic acid on in vivo amidation of alpha-melanocyte stimulating hormone in guinea pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Hilsted, L

    1988-01-01

    The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (alpha MSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 +/- 0.11 mumol/g tissue (mean +/- SD) in the pituitary and 0.34 +/- 0.07 mumol....../g tissue in the cerebral cortex from the depleted animals versus 7.58 +/- 0.08 and 1.51 +/- 0.32 mumol/g tissue, respectively, in the control animals. In the pituitaries from the animals depleted of ascorbate (N = 4), the relative amount of alpha MSH was reduced to approximately half the values obtained......-39) immunoreactivity was observed in the depleted guinea pigs. Gel chromatography and reversed-phase high-performance luquid chromatography showed that the alpha MSH and ACTH (1-14) immunoreactivity was of low molecular weight and partly mono- or diacetylated. Depletion of ascorbic acid had no influence on the degree...

  5. Retinol, alpha-tocopherol and fatty acid content in Bulgarian black Sea fish species

    Directory of Open Access Journals (Sweden)

    Stancheva, M.

    2012-06-01

    Full Text Available The aim of the present study was to measure and evaluate the total lipids, fatty acid profile, retinol content and alpha-tocopherol content in the edible tissue of four commercially important fish species from the Bulgarian Black sea: Sprat (Sprattus sprattus, Round Goby (Neogobius rattan, Black Sea Horse Mackerel (Trahurus medditeraneus ponticus and Shad (Alosa pontica. Fat soluble vitamins were analyzed simultaneously using an HPLC system. The highest content of retinol was established in the Sprat (142.3 ± 4.4 μg/100g and the highest content of alphatocopherol was found in the Black Sea Horse Mackerel (1112.7 ± 39.2 μg/100g. The fatty acid (FA composition was analyzed by GC/MS. The content of omega 3 (n3 FAs was significantly higher (p , 0.001 than the content of omega 6 (n6 FAs in each of the analyzed fish samples. The n6/n3 FA ratio was within the recommended range (0.20–1.50 for Sprat, Round Goby and Shad. Relatively high levels of retinol and alpha-tocopherol, FA composition, n3/n6 FA and PUFA/SFA ratios indicate that these fish species have good nutritional quality.

    El objeto de la investigación presentada es definir y comparar los lípidos totales, el perfil de ácidos grasos y el contenido de retinol y alfa-tocoferol en el tejido comestible de cuatro especies de peces con importancia comercial del Mar Negro búlgaro —espadín (Sprattus Sprattus, gobio de boca negra (Neogobius Melanostomus, chicharro (Trachurus Trachurus y sábalo del Mar Negro (Caspialosa Pontica. Dos vitaminas liposolubles son analizadas simultáneamente mediante cromatografía líquida de alta eficacia (HPLC. El contenido mayor de retinol se encuentra en el espadín (142.3 ± 4.4 μg/100g, y de alfa-tocoferol en el chicharro (1112.7 ± 39.2 μg/100g. El contenido de ácidos grasos ha sido analizado mediante cromatografía gaseosa/espectrometría de masas (GC/MS. El contenido de ácidos grasos (AG

  6. Effect of serum alpha-fetoprotein and uric acid levels on pregnancy outcome in late pregnancy women with hypertensive disorder

    Institute of Scientific and Technical Information of China (English)

    Xian-Feng Tan; Yu-Xiu Zhang

    2016-01-01

    Objective:To investigate the effects of serum alpha-fetoprotein and uric acid levels on pregnancy outcome in late pregnancy women with hypertensive disorder.Methods: One hundred and twenty-six cases of hypertensive disorder complicating pregnancy were rolled into the observation group, and 80 healthy pregnant women were rolled into the as control group. The relationship between serum alpha-fetoprotein and uric acid levels and adverse pregnancy outcomes were compared between the two groups.Results: Compared with the control group, the serum levels of AFP and serum uric acid were significantly higher in the observation group, and the differences were statistically significant (P<0.01). In the observation group, with the increase of blood pressure, the serum AFP and uric acid levels were increased, which in the moderate sub-group and severe sub-group were significantly higher than those in mild sub-group, and the severe sub-group was significantly higher than that in the moderate sub-group (allP<0.05). The rate of preterm birth, premature rupture rate, placental abruption rate, fetal distress rate and cesarean section rate in the pregnant women with abnormal serum AFP and uric acid level were significantly higher than that of the normal serum AFP and uric acid group (P<0.05).Conclusions:The serum AFP and uric acid levels in the late pregnancy women with hypertensive disorder are significantly higher than those of the normal pregnant women, and are elevated remarkably as the blood pressure rising. When the serum AFP and uric acid levels are abnormal, the adverse outcomes of pregnancy and cesarean section rate increase significantly. Monitoring of serum AFP and uric acid levels is of importance.

  7. Regulation of alpha-1 acid glycoprotein synthesis by porcine hepatocytes in monolayer culture.

    Science.gov (United States)

    Caperna, T J; Shannon, A E; Stoll, M; Blomberg, L A; Ramsay, T G

    2015-07-01

    Alpha-1 acid glycoprotein (AGP, orosomucoid, ORM-1) is a highly glycosylated mammalian acute-phase protein, which is synthesized primarily in the liver and represents the major serum protein in newborn pigs. Recent data have suggested that the pig is unique in that AGP is a negative acute-phase protein in this species, and its circulating concentration appears to be associated with growth rate. The purpose of the present study was to investigate the regulation of AGP synthesis in hepatocytes prepared from suckling piglets and to provide a framework to compare its regulation with that of haptoglobin (HP), a positive acute-phase protein. Hepatocytes were isolated from preweaned piglets and maintained in serum-free monolayer culture for up to 72 h. The influences of hormones, cytokines, and redox modifiers on the expression and secretion of AGP and HP were determined by relative polymerase chain reaction and by measuring the concentration of each protein secreted into culture medium. The messenger RNA abundance and/or secretion of AGP protein was enhanced by interleukin (IL)-17a, IL-1, and resveratrol and inhibited by tumor necrosis factor-α (TNF), oncostatin M, and thyroid hormone (P < 0.05). HP expression and synthesis were upregulated by oncostatin M, IL-6, and dexamethasone and downregulated by TNF (P < 0.01). The overall messenger RNA expression at 24 h was in agreement with the secreted protein patterns confirming that control of these proteins in hepatocytes is largely transcriptional. Moreover, these data support the consideration that AGP is a negative acute-phase reactant and appears to be regulated by cytokines (with the exception of TNF) and hormones primarily in a manner opposite to that of the positive acute-phase protein, HP.

  8. Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids

    OpenAIRE

    C. Handschin.; Gnerre, C; Fraser, D. J.; Martinez-Jimenez, C.; Jover, R; Meyer, U A

    2005-01-01

    The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver ...

  9. Biphasic effect of alpha-linolenic acid on glucose-induced dysmorphogenesis and lipoperoxidation in whole rat embryo in culture.

    Science.gov (United States)

    Chirino-Galindo, Gladys; Barrera-Argüelles, Jorge-Israel; Trejo-González, Ninna-Leslie; Mejía-Zepeda, Ricardo; Palomar-Morales, Martín

    2017-03-18

    Type 1 diabetes mellitus complicated with pregnancy, know as diabetic embryopathy, is the cause of neonatal malformations and low for gestational age neonates. With the use of the whole-embryo culture system, it has been demonstrated that high glucose causes embryo dysmorphogenesis, and that oxidative stress appears to be the main mechanism. In recent years, beneficial effect of omega-3 fatty acids has been demonstrated in various diabetic models, and in diabetic complications. Since diabetic embryopathy is mediated probably through membrane lipoperoxidation, This study was designed to find if omega-3 fatty acids could ameliorate the effect of high glucose over the dysmorphogenesis of whole rat embryo in culture. Postimplantational rat embryos were cultured in hyperglycemic media, with addition of alpha-linolenic acid, and morphologic and morphometric parameters were registered. Also, lipoperoxidation and fatty acids composition were measured in cultured embryos. Growth of embryos cultured in presence of glucose was very affected, whereas lipoperoxidation was increased, and it was found that Triton X-100 causes similar results than glucose. Addition of low micromolar doses of alpha-linolenic acid overcome the effect of high glucose or Triton X-100, but higher doses does not ameliorates the effects of the carbohydrate or the detergent. Paradoxically, there are not significant changes in fatty acids composition, although the U/S fatty acids ratio shows an increasing tendency by high glucose and a normalizing tendency by omega-3 fatty acids. In conclusion, glucose and Triton X-100 induces in vitro dysmorphogenesis in post-implantational rat embryos associated with increased lipoperoxidation; and this nocive effect could be ameliorated by low micromolar doses of ALA.

  10. Theoretical analysis of kinetic isotope effects on proton transfer reactions between substituted alpha-methoxystyrenes and substituted acetic acids.

    Science.gov (United States)

    Wong, Kin-Yiu; Richard, John P; Gao, Jiali

    2009-10-01

    Primary kinetic isotope effects (KIEs) on a series of carboxylic acid-catalyzed protonation reactions of aryl-substituted alpha-methoxystyrenes (X-1) to form oxocarbenium ions have been computed using the second-order Kleinert variational perturbation theory (KP2) in the framework of Feynman path integrals (PI) along with the potential energy surface obtained at the B3LYP/6-31+G(d,p) level. Good agreement with the experimental data was obtained, demonstrating that this novel computational approach for computing KIEs of organic reactions is a viable alternative to the traditional method employing Bigeleisen equation and harmonic vibrational frequencies. Although tunneling makes relatively small contributions to the lowering of the free energy barriers for the carboxylic acid catalyzed protonation reaction, it is necessary to include tunneling contributions to obtain quantitative estimates of the KIEs. Consideration of anharmonicity can further improve the calculated KIEs for the protonation of substituted alpha-methoxystyrenes by chloroacetic acid, but for the reactions of the parent and 4-NO(2) substituted alpha-methoxystyrene with substituted carboxylic acids, the correction of anharmonicity overestimates the computed KIEs for strong acid catalysts. In agreement with experimental findings, the largest KIEs are found in nearly ergoneutral reactions, DeltaG(o) approximately 0, where the transition structures are nearly symmetric and the reaction barriers are relatively low. Furthermore, the optimized transition structures are strongly dependent on the free energy for the formation of the carbocation intermediate, that is, the driving force DeltaG(o), along with a good correlation of Hammond shift in the transition state structure.

  11. The implications of particle energy and acidic media on gross alpha and gross beta determination using liquid scintillation

    Energy Technology Data Exchange (ETDEWEB)

    Zapata-Garcia, D. [Laboratori de Radiologia Ambiental (LRA), Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques, 1-11 Planta 3, E-08028 Barcelona (Spain); Llaurado, M., E-mail: montse.llaurado@ub.edu [Laboratori de Radiologia Ambiental (LRA), Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques, 1-11 Planta 3, E-08028 Barcelona (Spain); Rauret, G. [Laboratori de Radiologia Ambiental (LRA), Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques, 1-11 Planta 3, E-08028 Barcelona (Spain)

    2012-04-15

    The interaction of humans with radioactivity present in the environment from natural and artificial sources necessitates an evaluation of its risk on human health. Gross alpha and gross beta activities can provide a rapid evaluation of the radioactive content of a sample and can be simultaneously determined by using liquid scintillation counters. However, calibration of the liquid scintillation counter is required and is affected by many factors, such as particle energy and the acidity of the media. This study investigates what effect the particle energy used for calibration has on misclassification and how to account for this misclassification in routine measurements. The variability in measurement produced by the final pH, as well as any acids used in sample treatment, was also studied. These results showed that the most commonly used acid for these types of analyses, HNO{sub 3}, produced a high amount of misclassifications at very low pH. The results improved when HCl was used to adjust the sample to low pH. - Highlights: Black-Right-Pointing-Pointer We study the effect of alpha and beta energies on PSA optimisation. Black-Right-Pointing-Pointer The optimum PSA shifts to higher values as the alpha energy increases. Beta energies do not affect it. Black-Right-Pointing-Pointer We study the effect of pH on the simultaneous determination of gross alpha/beta activities. Black-Right-Pointing-Pointer HNO{sub 3} produces a high amount of misclassification at very low pH. Black-Right-Pointing-Pointer The results improve when HCl is used to adjust the sample to low pH.

  12. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Science.gov (United States)

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity.

  13. Sec61alpha synthesis is enhanced during translocation of nascent chains of collagen type IV in F9 teratocarcinoma cells after retinoic acid treatment

    Directory of Open Access Journals (Sweden)

    L.R. Ferreira

    2003-01-01

    Full Text Available Nascent procollagen peptides and other secretory proteins are transported across the endoplasmic reticulum (ER membrane through a protein-conducting channel called translocon. Sec61alpha, a multispanning membrane translocon protein, has been implicated as being essential for translocation of polypeptide chains into the cisterns of the ER. Sec61alpha forms a protein complex with collagen and Hsp47, an ER-resident heat shock protein that binds specifically to collagen. However, it is not known whether Sec61alpha is ubiquitously produced in collagen-producing F9 teratocarcinoma cells or under heat shock treatment. Furthermore, the production and utilization of Sec61alpha may depend on the stage of cell differentiation. Cultured F9 teratocarcinoma cells are capable of differentiation in response to low concentrations of retinoic acid. This differentiation results in loss of tumorigenicity. Mouse F9 cells were grown in culture medium at 37ºC and 43ºC (heat shock treatment treated or not with retinoic acid, and labeled in certain instances with 35S-methionine. Membrane-bound polysomes of procollagen IV were then isolated. Immunoprecipitation and Western blot analysis were performed using polyclonal antibodies against collagen IV, Hsp47 and Sec61alpha. Under retinoic acid-untreated conditions, F9 cells produced undetectable amounts of Sec61alpha. Sec61alpha, Hsp47 and type IV collagen levels were increased after retinoic acid treatment. Heat shock treatment did not alter Sec61alpha levels, suggesting that Sec61alpha production is probably not affected by heat shock. These data indicate that the enhanced production of Sec61alpha in retinoic acid-induced F9 teratocarcinoma cells parallels the increased synthesis of Hsp47 and collagen type IV.

  14. Zeolite-catalysed preparation of alpha-hydroxy carboxylic acids and esters thereof

    DEFF Research Database (Denmark)

    2010-01-01

    A process for the production of lactic acid and 2-hydroxy-3-butenoic acid or esters thereof by conversion of glucose, fructose, sucrose, xylose and glycolaldehyde dissolved in a solvent in presence of a solid Lewis acidic catalyst.......A process for the production of lactic acid and 2-hydroxy-3-butenoic acid or esters thereof by conversion of glucose, fructose, sucrose, xylose and glycolaldehyde dissolved in a solvent in presence of a solid Lewis acidic catalyst....

  15. Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on lipopolysaccharide-induced tumor necrosis factor-alpha release in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Giovannini, L; Migliori, M; Filippi, C; Origlia, N; Panichi, V; Falchi, M; Bertelli, A A E; Bertelli, A

    2002-01-01

    The objective of this study was to assess whether tyrosol and caffeic acid are able to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha release. TNF is one of the most important cytokines involved in inflammatory reactions. The results show that both tyrosol and caffeic acid are able to inhibit LPS-induced TNF-alpha release from human monocytes, even at low doses. Their mechanisms of action are discussed and we conclude that high doses of the two compounds are not required to achieve effective inhibition of inflammatory reactions due to TNF-alpha release.

  16. N-glycans of recombinant human acid alpha-glucosidase expressed in the milk of transgenic rabbits.

    Science.gov (United States)

    Jongen, Susanne P; Gerwig, Gerrit J; Leeflang, Bas R; Koles, Kate; Mannesse, Maurice L M; van Berkel, Patrick H C; Pieper, Frank R; Kroos, Marian A; Reuser, Arnold J J; Zhou, Qun; Jin, Xiaoying; Zhang, Kate; Edmunds, Tim; Kamerling, Johannis P

    2007-06-01

    Pompe disease is a lysosomal glycogen storage disorder characterized by acid alpha-glucosidase (GAA) deficiency. More than 110 different pathogenic mutations in the gene encoding GAA have been observed. Patients with this disease are being treated by intravenous injection of recombinant forms of the enzyme. Focusing on recombinant approaches to produce the enzyme means that specific attention has to be paid to the generated glycosylation patterns. Here, human GAA was expressed in the mammary gland of transgenic rabbits. The N-linked glycans of recombinant human GAA (rhAGLU), isolated from the rabbit milk, were released by peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase F. The N-glycan pool was fractionated and purified into individual components by a combination of anion-exchange, normal-phase, and Sambucus nigra agglutinin-affinity chromatography. The structures of the components were analyzed by 500 MHz one-dimensional and 600 MHz cryo two-dimensional (total correlation spectroscopy [TOCSY] nuclear Overhauser enhancement spectroscopy) (1)H nuclear magnetic resonance spectroscopy, combined with two-dimensional (31)P-filtered (1)H-(1)H TOCSY spectroscopy, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and high-performance liquid chromatography (HPLC)-profiling of 2-aminobenzamide-labeled glycans combined with exoglycosidase digestions. The recombinant rabbit glycoprotein contained a broad array of different N-glycans, comprising oligomannose-, hybrid-, and complex-type structures. Part of the oligomannose-type glycans showed the presence of phospho-diester-bridged N-acetylglucosamine. For the complex-type glycans (partially) (alpha2-6)-sialylated (nearly only N-acetylneuraminic acid) diantennary structures were found; part of the structures were (alpha1-6)-core-fucosylated or (alpha1-3)-fucosylated in the upper antenna (Lewis x). Using HPLC-mass spectrometry of glycopeptides, information was generated with respect to the

  17. Weak and saturable protein-surfactant interactions in the denaturation of apo-alpha-lactalbumin by acidic and lactonic sophorolipid

    Directory of Open Access Journals (Sweden)

    Kell K Andersen

    2016-11-01

    Full Text Available Biosurfactants are of growing interest as sustainable alternatives to fossil-fuel-derived chemical surfactants, particularly for the detergent industry. To realize this potential, it is necessary to understand how they affect proteins which they may encounter in their applications. However knowledge of such interactions is limited. Here we present a study of the interactions between the model protein apo-alpha-lactalbumin and the biosurfactant sophorolipid (SL produced by the yeast Starmerella bombicola. SL occurs both as an acidic and a lactonic form; the lactonic form (lactSL is sparingly soluble and has a lower critical micelle concentration than the acidic form (acidSL. We show that acidSL affects apo-aLA in a similar way to the related glycolipid biosurfactant rhamnolipid (RL, with the important difference that RL is also active below the cmc in contrast to acidSL. Using isothermal titration calorimetry data, we show that acidSL has weak and saturable interactions with apo-aLA at low concentrations; due to the relatively low cmc of acidSL (which means that the monomer concentration is limited to ca. 0-1 mM SL, it is only possible to observe interactions with monomeric acidSL at high apo-aLA concentrations. However, the denaturation kinetics of apo-aLA in the presence of acidSL are consistent with a collaboration between monomeric and micellar surfactant species, similar to RL and nonionic or zwitterionic surfactants. Inclusion of lactSL as mixed micelles with acidSL lowers the cmc and this effectively reduces the rate of unfolding, emphasizing that SL like other biosurfactants is a gentle anionic surfactant. Our data highlight the potential of these biosurfactants for future use in the detergent industry.

  18. Relationship between physicochemical parameters of alpha-amino acids and those of the chlorinated solvents in the case of the L/L partition as supra molecular complexes

    Energy Technology Data Exchange (ETDEWEB)

    Oana popescu, D.; Constantinescu, T.; Mutihac, L.

    1997-09-01

    In order to explain the dependence of the distribution coefficient (D) between water and three different chlorinated solvents (methylene chloride, chloroform and 1,2-dichloroethane) of some alpha-amino acids (leucine, tryptophane, phenylalanine, methionine, valine and isoleucine), as supramolecular complexes of [EC...R-CH-(NH{sub 3})-COOH]``+A``- type, (EC=18-C-6; A``-=the anion originated in tropaeoline 00), a correlation was established by means of a multilinear regression analysis performed between different characteristics of the alpha-amino acids and those of the solvents involved. This study evidence a good correlation (r>0.81) between some of the characteristics of alpha-amino acids (pi, pH, pKa{sub 2}), and of the solvent Sigma Beta``H{sub 2}, pi``H{sub 2} R``H{sub 2} or sigma alpha``H{sub 2}, just mentioned. (Author) 21 refs.

  19. Effects of the combination of hydrophobic polypeptides, iso-alpha acids, and malto-oligosaccharides on beer foam stability.

    Science.gov (United States)

    Ferreira, Isabel M P L V O; Jorge, Kátia; Nogueira, Luciana C; Silva, Filipe; Trugo, Luiz C

    2005-06-15

    The influence of hydrophobic polypeptides concentrated in beer foam, together with the composition of iso-alpha acids and the content of malto-oligosaccharides in beer on foam stability, has been investigated. The objective was to find out whether a shortage of one of these positive contributors to foam stability could be compensated for by an increased presence of another or whether optimum levels of each contributor is necessary. For that purpose, an image analysis method to evaluate beer foam quality was developed. The foam collapse time was the parameter chosen to group beers according to their foam stability. Profiles of hydrophobic polypeptides that concentrate in beer foam, iso-alpha acids, and malto-oligosaccharides of 14 beer brands were acquired by high-performance liquid chromatography. Principal component analysis (PCA) was performed to show the relationship between beer brands and its composition. Beers that contained propylene glycol alginate as a foam enhancer showed high foam stability except for one beer, which had a low content of hydrophobic polypeptides, thereby highlighting the requirement of threshold levels of hydrophobic polypeptides to obtain stable foam. The data of samples that were devoid of a foam additive were subjected to a discriminant statistical analysis. Foam stability declined in proportion to decreases in hydrophobic polypeptides and to a lesser extent to decreases in iso-alpha-acid contents. Apparently, the content of malto-oligosaccharides were found to have no major influence on foam stability. The model of discriminate analysis was found to explain 100% of the variance in data with 85.2% success in classifying all samples according to the model, suggesting that foam stability is mainly governed by the beer constituents evaluated in this study.

  20. Lectin-like receptor for alpha 1-acid glycoprotein in the epithelium of the rat prostate gland and seminal vesicles

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    BACKGROUND: A receptor for alpha 1-acid glycoprotein glycoforms AGP-B and AGP-C in the epithelium of the rat prostate gland and seminal vesicles is described. METHODS: The interaction between AGP-glycoforms and their receptor is a lectin-like interaction confirmed by inhibition of the binding...... in rat prostate and seminal vesicles. The localization of the AGP lectin receptor is compared to the localization of glycoprotein AGP, and small differences are found. CONCLUSIONS: It is proposed the AGP receptors in the prostate and seminal vesicles belong to a group of lectins in the control...

  1. The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex.

    Science.gov (United States)

    Wu, Hui-Qiu; Pereira, Edna F R; Bruno, John P; Pellicciari, Roberto; Albuquerque, Edson X; Schwarcz, Robert

    2010-01-01

    The cognitive deficits seen in schizophrenia patients are likely related to abnormal glutamatergic and cholinergic neurotransmission in the prefrontal cortex. We hypothesized that these impairments may be secondary to increased levels of the astrocyte-derived metabolite kynurenic acid (KYNA), which inhibits alpha7 nicotinic acetylcholine receptors (alpha7AChR) and may thereby reduce glutamate release. Using in vivo microdialysis in unanesthetized rats, we show here that nanomolar concentrations of KYNA, infused directly or produced in situ from its bioprecursor kynurenine, significantly decrease extracellular glutamate levels in the prefrontal cortex. This effect was prevented by the systemic administration of galantamine (3 mg/kg) but not by donepezil (2 mg/kg), indicating that KYNA blocks the allosteric potentiating site of the alpha7AChR, which recognizes galantamine but not donepezil as an agonist. In separate rats, reduction of prefrontal KYNA formation by (S)-4-ethylsulfonyl benzoylalanine, a specific inhibitor of KYNA synthesis, caused a significant elevation in extracellular glutamate levels. Jointly, our results demonstrate that fluctuations in endogenous KYNA formation bidirectionally influence cortical glutamate concentrations. These findings suggest that selective attenuation of cerebral KYNA production, by increasing glutamatergic tone, might improve cognitive function in individuals with schizophrenia.

  2. Immunolocalization of alpha-keratins and associated beta-proteins in lizard epidermis shows that acidic keratins mix with basic keratin-associated beta-proteins.

    Science.gov (United States)

    Alibardi, Lorenzo

    2014-07-01

    The differentiation of the corneous layers of lizard epidermis has been analyzed by ultrastructural immunocytochemistry using specific antibodies against alpha-keratins and keratin associated beta-proteins (KAbetaPs, formerly indicated as beta-keratins). Both beta-cells and alpha-cells of the corneous layer derive from the same germinal layer. An acidic type I alpha-keratin is present in basal and suprabasal layers, early differentiating clear, oberhautchen, and beta-cells. Type I keratin apparently disappears in differentiated beta- and alpha-layers of the mature corneous layers. Conversely, a basic type II alpha-keratin rich in glycine is absent or very scarce in basal and suprabasal layers and this keratin likely does not pair with type I keratin to form intermediate filaments but is weakly detected in the pre-corneous and corneous alpha-layer. Single and double labeling experiments show that in differentiating beta-cells, basic KAbetaPs are added and replace type-I keratin to form the hard beta-layer. Epidermal alpha-keratins contain scarce cysteine (0.2-1.4 %) that instead represents 4-19 % of amino acids present in KAbetaPs. Possible chemical bonds formed between alpha-keratins and KAbetaPs may derive from electrostatic interactions in addition to cross-linking through disulphide bonds. Both the high content in glycine of keratins and KAbetaPs may also contribute to increase the hydrophobicy of the beta- and alpha-layers and the resistance of the corneous layer. The increase of gly-rich KAbetaPs amount and the bonds to the framework of alpha-keratins give rise to the inflexible beta-layer while the cys-rich KAbetaPs produce a pliable alpha-layer.

  3. Studies on N-terminal glycation of peptides in hypoallergenic infant formulas: quantification of alpha-N-(2-furoylmethyl) amino acids.

    Science.gov (United States)

    Penndorf, Ilka; Biedermann, Daniela; Maurer, Sarah V; Henle, Thomas

    2007-02-01

    To obtain information about the extent of the early Maillard reaction between the N-termini of peptides and lactose, alpha-N-(2-furoylmethyl) amino acids (FMAAs) were quantified together with epsilon-N-(2-furoylmethyl)lysine (furosine) in acid hydrolyzates of hypoallergenic infant formulas, conventional infant formulas, and human milk samples using RP-HPLC with UV-detection. FMAAs are formed during acid hydrolysis of peptide-bound N-terminal Amadori products (APs), and furosine is formed from the Amadori products of peptide-bound lysine. Unambiguous identification was achieved by means of LC/MS and UV-spectroscopy using independently prepared reference material. The extent of acid-induced conversion of APs to FMAAs was studied by RP-HPLC with chemiluminescent nitrogen detection (CLND). Depending on the corresponding alpha-N-lactulosyl amino acid, between 6.0% and 18.1% of FMAAs were formed during hydrolysis for 23 h at 110 degrees C in 8 N HCl. From epsilon-N-lactulosyllysine, 50% furosine is formed under these conditions. Whereas furosine was detectable in all assayed samples, five different FMAAs, alpha-FM-Lys, alpha-FM-Ala, alpha-FM-Val, alpha-FM-Ile, and alpha-FM-Leu, were exclusively detected in acid hydrolyzates of hypoallergenic infant formulas in amounts ranging from 35 to 396 mumol/100 g protein. Taking the conversion factors into account, modification of N-terminal amino acids in peptides by reducing carbohydrates was between 0.3% and 8.4%. This has to be considered within the discussion concerning the nutritional quality of peptide-containing foods.

  4. Asymmetric Synthesis of Carbon-11 Labelled alpha-Amino Acids for PET

    NARCIS (Netherlands)

    Popkov, Alexander; Elsinga, Philip H.

    2013-01-01

    For PET applications in oncological and neurological diagnostics, amino acids have been studied both clinically and pre-clinically during the last 35 years. Nowadays two applications of labelled amino acids for visualisation of tumours attract the main attention: [C-11] or [F-18]amino acids as subst

  5. The peroxisome proliferator-activated receptor alpha-selective activator ciprofibrate upregulates expression of genes encoding fatty acid oxidation and ketogenesis enzymes in rat brain.

    Science.gov (United States)

    Cullingford, Tim E; Dolphin, Colin T; Sato, Hitoshi

    2002-04-01

    Activated peroxisome proliferator activated receptor alpha (PPAR alpha) protects against the cellular inflammatory response, and is central to fatty acid-mediated upregulation of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS). We have previously demonstrated both PPAR alpha and mHS expression in brain, implying that brain-targeted PPAR alpha activators may likewise up-regulate mHS expression in brain. Thus, to attempt pharmacological activation of brain PPAR alpha in vivo, we have administered to rats two drugs with previously defined actions in rat brain, namely the PPAR alpha-selective activator ciprofibrate and the pan-PPAR activator valproate. Using the sensitive and discriminatory RNase protection co-assay, we demonstrate that both ciprofibrate and valproate induce mHS expression in liver, the archetypal PPAR alpha-expressing organ. Furthermore, ciprofibrate potently increases mHS mRNA abundance in rat brain, together with lesser increases in two other PPAR alpha-regulated mRNAs. Thus we demonstrate, for the first time, up-regulation of expression of PPAR alpha-dependent genes including mHS in brain, with implications in the increased elimination of neuro-inflammatory lipids and concomitant increased production of neuro-protective ketone bodies.

  6. Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase during exercise in man

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; MacLean, D A; Saltin, B

    1996-01-01

    1. Exercise leads to activation (dephosphorylation) of the branched-chain alpha-keto acid dehydrogenase (BCKADH). Here we investigate the effect of low pre-exercise muscle glycogen content and of branched-chain amino acid (BCAA) ingestion on the activity of BCKADH at rest and after 90 min of one......-leg knee-extensor exercise at 65% maximal one-leg power output in five subjects. 2. Pre-exercise BCAA ingestion (308 mg BCAAs (kg body wt)-1) caused an increased muscle BCAA uptake, a higher intramuscular BCAA concentration and activation of BCKADH both at rest (9 +/- 1 versus 25 +/- 5% for the control...... and BCAA test, respectively) and after exercise (27 +/- 4 versus 54 +/- 7%). 3. At rest the percentage active BCKADH was not different, 6 +/- 2% versus 5 +/- 1%, in the normal and low glycogen content leg (392 +/- 21 and 147 +/- 34 mumol glycosyl units (g dry muscle)-1, respectively). The post...

  7. Isolation, structure determination and biological activity of 25-epi, 3{alpha}-carboxyacetylquercinic acid in daedalea dickinsii

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kang Gyu; Min, Tae Jin [Dongguk Univ., Seoul (Korea, Republic of)

    2000-02-01

    In order to develope bioactive substances, dried fruit body of Daedalea dickinsii collected from Taeback mountain was extracted with ethanol. The compounds 1 and 2 were purified by solvent extraction, silica gel column chromatography and recrystallization from the ethanol extracts. Melting point, molecular weight and molar extinction coefficient of the compound 1 were estimated to be 167{approx}168 .deg. C, 572 and 5,040 at 208 nm. The structure of this compound 1 has been elucidated to be 24S, 25S, 3{alpha}-carboxyacetylquercinic acid using spectroscopic properties. This compound showed antibiotic activities against fungi, yeasts and bacteria and it also showed anticancer activity(IC{sub 50}=64.5 {mu}M/ml) against Korean stomach cancer cell. Melting point, molecular weight and molar extinction coefficient of the compound 2 were estimated to be 233{approx}235 .deg. C, 572 and 5,080 at 208 nm. The structure of this compound was elucidated to be 24S, 25R, 3{alpha}-carboxyacetylquercinic acid. The compound 2 showed different antibiotic activities with the compound 1.

  8. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors : the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study

    NARCIS (Netherlands)

    Bemelmans, W.J.; Broer, J.; Feskens, E.J.; Smit, A.J.; Muskiet, F.A.; Lefrandt, J.D.; Bom, V.J.; May, J.F.; Meyboom-de Jong, B.

    2002-01-01

    Background: The effect of long-term increased intakes of alpha-linolenic acid (ALA; 18:3n-3) on cardiovascular risk factors is unknown. Objectives: Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease (IHD)

  9. Corrosion inhibition of mild steel in 1 M HCl solution by henna extract: A comparative study of the inhibition by henna and its constituents (Lawsone, Gallic acid, {alpha}-D-Glucose and Tannic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Ostovari, A. [Technical Inspection Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of)], E-mail: A.Ostovari@gmail.com; Hoseinieh, S.M.; Peikari, M. [Technical Inspection Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of); Shadizadeh, S.R. [Petroleum Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of); Hashemi, S.J. [Technical Inspection Engineering Department, Petroleum University of Technology, Abadan (Iran, Islamic Republic of)

    2009-09-15

    The inhibitive action of henna extract (Lawsonia inermis) and its main constituents (lawsone, gallic acid, {alpha}-D-Glucose and tannic acid) on corrosion of mild steel in 1 M HCl solution was investigated through electrochemical techniques and surface analysis (SEM/EDS). Polarization measurements indicate that all the examined compounds act as a mixed inhibitor and inhibition efficiency increases with inhibitor concentration. Maximum inhibition efficiency (92.06%) is obtained at 1.2 g/l henna extract. Inhibition efficiency increases in the order: lawsone > henna extract > gallic acid > {alpha}-D-Glucose > tannic acid. Also, inhibition mechanism and thermodynamic parameters are discussed.

  10. Determination of (alpha)-dialkylamino acids and their Enantiomers in Geological Samples by High-Performance Liquid Chromatography after Dervatization with a Chiral Adduct of (omicron)-Phthaldialdehyde

    Science.gov (United States)

    Zhoa, Meixun; Bada, Jeffrey L.

    1995-01-01

    Derivatization with (omicron)-phthaldialdehyde (OPA) and the chiral thiol N-acetyl-L-cysteine (NAC) is a convenient and sensitive technique for the HPLC detection and resolution of protein amino acid enantiomers. The kinetics of the reaction of OPA-NAC with (alpha)-dialkylamino acids was investigated. The fluorescence yield of (alpha)-dialkylamino acids was only about 10% of that of protein amino acids when the derivatization was carried out at room temperature for 1-2 min, which is the procedure generally used for protein amino acid analyses. The fluorescence yield of (alpha)-dialkylamino acids can be enhanced by up to ten-fold when the derivatization reaction time is increased to 15 min at room temperature. The OPA-NAC technique was optimized for the detection and enantiomeric resolution of a-dialkylamino acids in geological samples which contain a large excess of protein amino acids. The estimated detection limit for a-dialkylamino acids is 1-2 pmol, comparable to that for protein amino acids.

  11. At low concentrations, 3,4-dihydroxyphenylacetic acid (DOPAC) binds non-covalently to alpha-synuclein and prevents its fibrillation.

    Science.gov (United States)

    Zhou, Wenbo; Gallagher, Amy; Hong, Dong-Pyo; Long, Chunmei; Fink, Anthony L; Uversky, Vladimir N

    2009-05-01

    Several studies have shown that catecholamines can inhibit the fibrillation of alpha-synuclein (alpha-Syn), a small presynaptic protein whose aggregation is believed to be a critical step in the etiology of Parkinson's disease and several other neurodegenerative disorders. However, the mechanism of this inhibition is uncertain. We show here that substoichiometric concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a normal product of the metabolism of dopamine, can inhibit the fibrillation of alpha-Syn, due to non-covalent binding of DOPAC to alpha-Syn monomer. Intriguingly, the presence of alpha-Syn accelerates the spontaneous oxidation of DOPAC, and the oxidized form of DOPAC (the quinone) is responsible for the fibrillation inhibition. In addition, the presence of DOPAC leads to the oxidation of the methionine residues of alpha-Syn, probably due to the H(2)O(2) production as a by-product of DOPAC oxidation. The lack of fibrillation results from the formation of stable oligomers, which are very similar to those observed transiently at early stages of the alpha-Syn fibrillation. A possible explanation for this phenomenon is that DOPAC stabilizes the normally transient oligomers and prevents them from subsequent fibril formation. The analysis of the alpha-Syn Y39W variant suggests that DOPAC binds non-covalently to the same N-terminal region of alpha-Syn as lipid vesicles, probably in the vicinity of residue 39. In contrast to the compounds with 1,2-dihydroxyphenyl groups (DOPAC and catechol), their 1,4-dihydroxyphenyl isomers (hydroquinone and homogentisic acid) are able to modify alpha-Syn covalently, probably due to the less steric hindrance in the Michael addition.

  12. Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.

    Science.gov (United States)

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer.

  13. Axolotl hemoglobin: cDNA-derived amino acid sequences of two alpha globins and a beta globin from an adult Ambystoma mexicanum.

    Science.gov (United States)

    Shishikura, Fumio; Takeuchi, Hiro-aki; Nagai, Takatoshi

    2005-11-01

    Erythrocytes of the adult axolotl, Ambystoma mexicanum, have multiple hemoglobins. We separated and purified two kinds of hemoglobin, termed major hemoglobin (Hb M) and minor hemoglobin (Hb m), from a five-year-old male by hydrophobic interaction column chromatography on Alkyl Superose. The hemoglobins have two distinct alpha type globin polypeptides (alphaM and alpham) and a common beta globin polypeptide, all of which were purified in FPLC on a reversed-phase column after S-pyridylethylation. The complete amino acid sequences of the three globin chains were determined separately using nucleotide sequencing with the assistance of protein sequencing. The mature globin molecules were composed of 141 amino acid residues for alphaM globin, 143 for alpham globin and 146 for beta globin. Comparing primary structures of the five kinds of axolotl globins, including two previously established alpha type globins from the same species, with other known globins of amphibians and representatives of other vertebrates, we constructed phylogenetic trees for amphibian hemoglobins and tetrapod hemoglobins. The molecular trees indicated that alphaM, alpham, beta and the previously known alpha major globin were adult types of globins and the other known alpha globin was a larval type. The existence of two to four more globins in the axolotl erythrocyte is predicted.

  14. Fractionation of Suwannee River fulvic acid and Aldrich humic acid on {alpha}-Al{sub 2}O{sub 3}: spectroscopic evidence

    Energy Technology Data Exchange (ETDEWEB)

    Claret, F.; Reiller, P.E. [CEA Saclay, DEN/DANS/DPC/SECR, Lab Speciat Radionucleides et Mol, F-91191 Gif Sur Yvette, (France); Claret, F. [BRGM, Environm and Process Div, F-45060 Orleans, (France); Schaefer, T. [Forschungszentrum Karlsruhe, Inst Nukl Entsorgung INE, D-76021 Karlsruhe, (Germany); Brevet, J. [Univ Evry Val Essonne, Lab Analyse et Environm Biol et Environm, CNRS, UMR 8587, F-91025 Evry, (France)

    2008-07-01

    Sorptive fractionation of Suwannee River Fulvic Acid (SRFA) and Purified Aldrich Humic Acid (PAHA) on {alpha}-Al{sub 2}O{sub 3} at pH 6 was probed in the supernatant using different spectroscopic techniques. Comparison of dissolved organic carbon (DOC) analysis with UV/vis spectrophotometric measurements at 254 nm, including specific UV absorbance (SUVA) calculation, revealed a decrease in chromophoric compounds for the non-sorbed extracts after a 24 h contact time. This fractionation, only observable below a certain ratio between initial number of sites of humic substances and of {alpha}-Al{sub 2}O{sub 3}, seems to indicate a higher fractionation for PAHA. C(1s) near-edge X-ray absorption fine structure spectroscopy (NEXAFS) confirmed this trend and points to a decrease in phenolic moieties in the supernatant and to an eventual increase in phenolic moieties on the surface. Time-resolved luminescence spectroscopy (TRLS) of Eu(III) as luminescent probe showed a decrease in the ratio between the {sup 5}D{sub 0}{yields}{sup 7}F{sub 2} and {sup 5}D{sub 0}{yields}{sup 7}F{sub 1} transitions for the fractionated organic matter (OM) that is thought to be associated with a lower energy transfer from the OM to Eu(III) due to the loss of polar aromatics. These modifications in the supernatant are a hint for the modification of sorbed humic extracts on the surface. (authors)

  15. Spectroscopic Studies of R(+-α-Lipoic Acid—Cyclodextrin Complexes

    Directory of Open Access Journals (Sweden)

    Naoko Ikuta

    2014-11-01

    Full Text Available α-Lipoic acid (ALA has a chiral center at the C6 position, and exists as two enantiomers, R(+-ALA (RALA and S(−-ALA (SALA. RALA is naturally occurring, and is a cofactor for mitochondrial enzymes, therefore playing a major role in energy metabolism. However, RALA cannot be used for pharmaceuticals or nutraceuticals because it readily polymerizes via a 1,2-dithiolane ring-opening when exposed to light or heat. So, it is highly desired to find out the method to stabilize RALA. The purpose of this study is to provide the spectroscopic information of stabilized RALA and SALA through complexation with cyclodextrins (CDs, α-CD, β-CD and γ-CD and to examine the physical characteristics of the resultant complexes in the solid state. The RALA-CD structures were elucidated based on the micro fourier transform infrared (FT-IR and Raman analyses. The FT-IR results showed that the C=O stretching vibration of RALA appeared at 1717 cm−1 and then shifted on formation of the RALA-CD complexes. The Raman spectra showed that the S–S and C–S stretching vibrations for RALA at 511 cm−1 (S–S, 631 cm−1 (C–S and 675 cm−1 (C–S drastically weakened and almost disappeared upon complexation with CDs. Several peaks indicative of O–H vibrations also shifted or changed in intensity. These results indicate that RALA and CDs form host-guest complexes by interacting with one another.

  16. Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats.

    Science.gov (United States)

    Rincón-Cervera, Miguel Ángel; Valenzuela, Rodrigo; Hernandez-Rodas, María Catalina; Barrera, Cynthia; Espinosa, Alejandra; Marambio, Macarena; Valenzuela, Alfonso

    2016-08-01

    Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n-3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Δ-5 and Δ-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-α and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-α, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA.

  17. X-ray structure of Pur-alpha reveals a Whirly-like fold and an unusual nucleic-acid binding surface.

    Science.gov (United States)

    Graebsch, Almut; Roche, Stéphane; Niessing, Dierk

    2009-11-03

    The PUR protein family is a distinct and highly conserved class that is characterized by its sequence-specific RNA- and DNA-binding. Its best-studied family member, Pur-alpha, acts as a transcriptional regulator, as host factor for viral replication, and as cofactor for mRNP localization in dendrites. Pur-alpha-deficient mice show severe neurologic defects and die after birth. Nucleic-acid binding by Pur-alpha is mediated by its central core region, for which no structural information is available. We determined the x-ray structure of residues 40 to 185 from Drosophila melanogaster Pur-alpha, which constitutes a major part of the core region. We found that this region contains two almost identical structural motifs, termed "PUR repeats," which interact with each other to form a PUR domain. DNA- and RNA-binding studies confirmed that PUR domains are indeed functional nucleic-acid binding domains. Database analysis show that PUR domains share a fold with the Whirly class of nucleic-acid binding proteins. Structural analysis combined with mutational studies suggest that a PUR domain binds nucleic acids through two independent surface regions involving concave beta-sheets. Structure-based sequence alignment revealed that the core region harbors a third PUR repeat at its C terminus. Subsequent characterization by small-angle x-ray scattering (SAXS) and size-exclusion chromatography indicated that PUR repeat III mediates dimerization of Pur-alpha. Surface envelopes calculated from SAXS data show that the Pur-alpha dimer consisting of repeats I to III is arranged in a Z-like shape. This unexpected domain organization of the entire core domain of Pur-alpha has direct implications for ssDNA/ssRNA and dsDNA binding.

  18. Inhibition of TNF-alpha induced cell death in human umbilical vein endothelial cells and Jurkat cells by protocatechuic acid.

    Science.gov (United States)

    Zhou-Stache, J; Buettner, R; Artmann, G; Mittermayer, C; Bosserhoff, A K

    2002-11-01

    The Chinese herb radix Salviae miltiorrhizae (RSM) is used in traditional Chinese medicine as a treatment for cardiovascular and cerebrovascular diseases. Several components of the plant extract from salvia mitorrhiza bunge have been determined previously, one of which is protocatechuic acid (PAC). It has been found, in the study, that PAC inhibited TNF-alpha-induced cell death of human umbilical vein endothelial cells (HUVECs) and Jurkat cells in a concentration of 100 microM when applied 2 h prior to TNF-alpha exposure. Molecular studies revealed that PAC activated NF-kappaB with a maximum effect after 30 min of treatment. Inhibition of NF-kappaB action by MG132 and NF-kappaB inhibitory peptide suppressed the cell-protective effect of PAC. Further, degradation of IkBalpha occurred in response to PAC treatment. The results provide evidence that activation of NF-kappaB plays an important role in mediating the cell-protecting effect of PAC on HUVECs and Jurkat cells. Further studies are required to test whether PAC, a component of radix salviae miltiorrhizae, could be useful in preventing in vivo cell death resulting from cardiovascular or cerebrovascular diseases.

  19. PLZF-RAR[alpha] fusion proteins generated from the variant t(11; 17)(q23; q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhu; Chen, Sai-Juan; Wang, Zhen-Yi (Shanghai Second Medical Univ. (China)); Guidez, F.; Rousselot, P.; Agadir, A.; Degos, L.; Chomienne, C. (Laboratoire de Biologie Cellulaire Hematopoietique, Paris (France)); Zelent, A. (Institute for Cancer Research, London (United Kingdom)); Waxman, S. (Mount Sinai Medical Center, New York, NY (United States))

    1994-02-01

    Recently, the authors described a recurrent variant translocation, t(11;17)(q23;q21), in acute promyelocytic leukemia (APL) which juxtaposes PLZF, a gene encoding a zinc finger protein, to RARA, encoding retinoic acid receptor [alpha] (RAR[alpha]). They have now cloned cDNAs encoding PLZF-RAR[alpha] chimeric proteins and studied their transactivating activities. In transient-expression assays, both the PLZF(A)-RAR[alpha] and PLZF(B)-RAR[alpha] fusion proteins like the PML-RAR[alpha] protein resulting from the well-known t(15;17) translocation in APL, antagonized endogenous and transfected wild-type RAR[alpha] in the presence of retinoic acid. Cotransfection assays showed that a significant repression of RAR[alpha] transactivation activity was obtained even with a very low PLZF-RAR[alpha]-expressing plasmid concentration. A [open quotes]dominant negative[close quotes] effect was observed with vectors expressing RAR[alpha] and retinoid X receptor [alpha] (RXR[alpha]). These abnormal transactivation properties observed in retinoic acid-sensitive myeloid cells strongly implicate the PLZF-RAR[alpha] fusion proteins in the molecular pathogenesis of APL.

  20. Incorporation of alpha-Ketoglutaric Acid as a Fixed Bed Scrubber Media for the Neutralization of Hydrazine Family Hypergolic Fuels

    Science.gov (United States)

    DeVor, R. W.; Santiago-Maldonado, E.; Parkerson, J. K.

    2010-01-01

    A candidate scrubber media, alpha-ketoglutaric acid (aKGA) adsorbed onto a silica-based substrate was examined as a potential alternative to the hydrazine-family hypergolic fuel neutralization techniques currently utilized at NASA/Kennedy Space Center (KSC). Helvenson et. al. has indicated that aKGA will react with hydrazines to produce non-hazardous, possibly biodegradable products. Furthermore, the authors have previously tested and demonstrated the use of aKGA aqueous solutions as a replacement neutralizing agent for citric acid, which is currently used as a scrubbing agent in liquid scrubbers at KSC. Specific properties examined include reaction efficiency, the loading capacity of aKGA onto various silica substrates, and the comparison of aKGA media performance to that of the citric acid vapor scrubber systems at KSC and a commercial vapor scrubber media. Preliminary investigations showed hydrophobic aerogel particles to be an ideal substrate for the deposition of the aKGA. Current studies have shown that the laboratory produced aKGA-Aerogel absorbent media are more efficient and cost effective than a commercially available fixed bed scrubber media, although much less cost effective than liquid-based citric acid scrubbers (although possibly safer and less labor intensive). A comparison of all three alternative scrubber technologies (liquid aKGA, solid-phase aKGA, and commercially available sorbent materials) is given considering both hypergolic neutralization capabilities and relative costs (as compared to the current citric acid scrubbing technology in use at NASA/KSC).

  1. Folic acid mediates activation of the pro-oncogene STAT3 via the Folate Receptor alpha.

    Science.gov (United States)

    Hansen, Mariann F; Greibe, Eva; Skovbjerg, Signe; Rohde, Sarah; Kristensen, Anders C M; Jensen, Trine R; Stentoft, Charlotte; Kjær, Karina H; Kronborg, Camilla S; Martensen, Pia M

    2015-07-01

    The signal transducer and activator of transcription 3 (STAT3) is a well-described pro-oncogene found constitutively activated in several cancer types. Folates are B vitamins that, when taken up by cells through the Reduced Folate Carrier (RFC), are essential for normal cell growth and replication. Many cancer cells overexpress a glycophosphatidylinositol (GPI)-anchored Folate Receptor α (FRα). The function of FRα in cancer cells is still poorly described, and it has been suggested that transport of folate is not its primary function in these cells. We show here that folic acid and folinic acid can activate STAT3 through FRα in a Janus Kinase (JAK)-dependent manner, and we demonstrate that gp130 functions as a transducing receptor for this signalling. Moreover, folic acid can promote dose dependent cell proliferation in FRα-positive HeLa cells, but not in FRα-negative HEK293 cells. After folic acid treatment of HeLa cells, up-regulation of the STAT3 responsive genes Cyclin A2 and Vascular Endothelial Growth Factor (VEGF) were verified by qRT-PCR. The identification of this FRα-STAT3 signal transduction pathway activated by folic and folinic acid contributes to the understanding of the involvement of folic acid in preventing neural tube defects as well as in tumour growth. Previously, the role of folates in these diseases has been attributed to their roles as one-carbon unit donors following endocytosis into the cell. Our finding that folic acid can activate STAT3 via FRα adds complexity to the established roles of B9 vitamins in cancer and neural tube defects.

  2. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent

    NARCIS (Netherlands)

    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Martini, I A; Muskiet, F A

    2000-01-01

    Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and docosahexaeno

  3. An antiaging skin care system containing alpha hydroxy acids and vitamins improves the biomechanical parameters of facial skin

    Directory of Open Access Journals (Sweden)

    Tran D

    2014-12-01

    Full Text Available Diana Tran, Joshua P Townley, Tanya M Barnes, Kerryn A Greive Ego Pharmaceuticals, Braeside, Victoria, Australia Background: The demand for antiaging products has dramatically increased in recent years, driven by an aging population seeking to maintain the appearance of youth. This study investigates the effects of an antiaging skin care system containing alpha hydroxy acids (AHAs in conjunction with vitamins B3, C, and E on the biomechanical parameters of facial skin. Methods: Fifty two volunteers followed an antiaging skin care regimen comprising of cleanser, eye cream, day moisturizer, and night moisturizer for 21 days. Wrinkle depth (Ry and skin roughness (Ra were measured by skin surface profilometry of the crow's feet area, and skin elasticity parameters R2 (gross elasticity, R5 (net elasticity, R6 (viscoelastic portion, and R7 (recovery after deformation were determined for facial skin by cutometer, preapplication and after 7, 14, and 21 days. Volunteers also completed a self-assessment questionnaire. Results: Compared to baseline, Ry and Ra significantly improved by 32.5% (P<0.0001 and 42.9% (P<0.0001, respectively, after 21 days of antiaging skin care treatment. These results were observed by the volunteers with 9 out of 10 discerning an improvement in skin texture and smoothness. Compared to baseline, R2 and R5 significantly increased by 15.2% (P<0.0001 and 12.5% (P=0.0449, respectively, while R6 significantly decreased by 17.7% (P<0.0001 after 21 days. R7 increased by 9.7% after 21 days compared to baseline but this was not significant over this time period. Conclusion: An antiaging skin care system containing AHAs and vitamins significantly improves the biomechanical parameters of the skin including wrinkles and skin texture, as well as elasticity without significant adverse effects. Keywords: alpha hydroxy acids, antiaging, nicotinamide, vitamin C, vitamin E, profilometry, cutometer

  4. Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels.

    Science.gov (United States)

    Barceló-Coblijn, Gwendolyn; Murphy, Eric J

    2009-11-01

    There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n-3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n-3 levels.

  5. In vitro and in vivo impairment of alpha2-adrenergic receptor-dependent antilipolysis by fatty acids in human adipose tissue.

    Science.gov (United States)

    Gesta, S; Hejnova, J; Berlan, M; Daviaud, D; Crampes, F; Stich, V; Valet, P; Saulnier-Blache, J S

    2001-12-01

    The aim of the present study was to study the influence of fatty acids on the adrenergic control of lipolysis both in vitro and in vivo. Human subcutaneous adipose tissue explants were cultured for 48 h in the presence of 100 microM bromopalmitate (BrPal), and lipolysis was measured in isolated adipocytes. In control conditions, beta-AR-dependent activation of lipolysis by epinephrine was almost undetectable, and could be fully restored by pharmacological blockade of alpha2-AR-dependent antilipolysis. After BrPal treatment, epinephrine became fully lipolytic and was no longer influenced by alpha2-AR-blockade. Radioligand binding analysis revealed that BrPal treatment led to a significant reduction in the coupling of alpha2-AR to G proteins. In parallel, a chronic and significant increase in plasma fatty acids resulting from a 4-day high-fat diet (HFD) was accompanied by an impairment of the amplifying effect of the alpha2-AR antagonist phentolamine on exercise-induced lipolysis (measured in the subcutaneous adipose tissue with the use of a microdialysis probe) normally observed after a low-fat diet. In conclusion, in vitro and in vivo studies showed that fatty acids impair alpha2-AR-dependent antilipolysis.

  6. Interleukin-1beta but not tumor necrosis factor-alpha potentiates neuronal damage by quinolinic acid: protection by an adenosine A2A receptor antagonist.

    Science.gov (United States)

    Stone, Trevor W; Behan, Wilhelmina M H

    2007-04-01

    Quinolinic acid is an agonist at glutamate receptors sensitive to N-methyl-D-aspartate (NMDA). It has been implicated in neural dysfunction associated with infections, trauma, and ischemia, although its neurotoxic potency is relatively low. This study was designed to examine the effects of a combination of quinolinic acid and the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Compounds were administered to the hippocampus of anesthetized male rats, animals being allowed to recover for 7 days before histological analysis of the hippocampus for neuronal damage estimated by counting of intact, healthy neurons. A low dose of quinolinic acid or IL-1beta produced no damage by itself, but the two together induced a significant loss of pyramidal neurons in the hippocampus. Higher doses produced almost total loss of pyramidal cells. Intrahippocampal TNF-alpha produced no effect alone but significantly reduced the neuronal loss produced by quinolinic acid. The adenosine A(2A) receptor antagonist ZM241385 reduced neuronal loss produced by the combinations of quinolinic acid and IL-1beta. The results suggest that simultaneous quinolinic acid and IL-1beta, both being induced by cerebral infection or injury, are synergistic in the production of neuronal damage and could together contribute substantially to traumatic, infective, or ischemic cerebral damage. Antagonism of adenosine A(2A) receptors protects neurons against the combination of quinolinic acid and IL-1beta.

  7. Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids.

    Science.gov (United States)

    Zollner, Gernot; Wagner, Martin; Moustafa, Tarek; Fickert, Peter; Silbert, Dagmar; Gumhold, Judith; Fuchsbichler, Andrea; Halilbasic, Emina; Denk, Helmut; Marschall, Hanns-Ulrich; Trauner, Michael

    2006-05-01

    The bile acid receptor farnesoid X receptor (FXR) is a key regulator of hepatic defense mechanisms against bile acids. A comprehensive study addressing the role of FXR in the coordinated regulation of adaptive mechanisms including biosynthesis, metabolism, and alternative export together with their functional significance is lacking. We therefore fed FXR knockout (FXR(-/-)) mice with cholic acid (CA) and ursodeoxycholic acid (UDCA). Bile acid synthesis and hydroxylation were assessed by real-time RT-PCR for cytochrome P-450 (Cyp)7a1, Cyp3a11, and Cyp2b10 and mass spectrometry-gas chromatography for determination of bile acid composition. Expression of the export systems multidrug resistance proteins (Mrp)4-6 in the liver and kidney and the recently identified basoalteral bile acid transporter, organic solute transporter (Ost-alpha/Ost-beta), in the liver, kidney, and intestine was also investigated. CA and UDCA repressed Cyp7a1 in FXR(+/+) mice and to lesser extents in FXR(-/-) mice and induced Cyp3a11 and Cyp2b10 independent of FXR. CA and UDCA were hydroxylated in both genotypes. CA induced Ost-alpha/Ost-beta in the liver, kidney, and ileum in FXR(+/+) but not FXR(-/-) mice, whereas UDCA had only minor effects. Mrp4 induction in the liver and kidney correlated with bile acid levels and was observed in UDCA-fed and CA-fed FXR(-/-) animals but not in CA-fed FXR(+/+) animals. Mrp5/6 remained unaffected by bile acid treatment. In conclusion, we identified Ost-alpha/Ost-beta as a novel FXR target. Absent Ost-alpha/Ost-beta induction in CA-fed FXR(-/-) animals may contribute to increased liver injury in these animals. The induction of bile acid hydroxylation and Mrp4 was independent of FXR but could not counteract liver toxicity sufficiently. Limited effects of UDCA on Ost-alpha/Ost-beta may jeopardize its therapeutic efficacy.

  8. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Directory of Open Access Journals (Sweden)

    Yifei Zhong

    Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  9. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Science.gov (United States)

    Zhong, Yifei; Wu, Yingwei; Liu, Ruijie; Li, Zhengzhe; Chen, Yibang; Evans, Todd; Chuang, Peter; Das, Bhaskar; He, John Cijiang

    2011-01-01

    Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  10. Alpha-picolinic Acid Activates Diverse Defense Responses of Salicylic Acid-, Jasmonic Acid/Ethylene- and Ca2 -dependent Pathways in Arabidopsis and Rice Suspension Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGHai-Kuo; ZHANGXin; LIQun; HEZu-Hua

    2004-01-01

    Alpha-picolinic acid (PA) is an apoptosis inducer in animal cells, and could elicit hypersensitiv eresponse (HR) in rice, a monocotyledonous model plant. Here we report that PA is an HR inducer in plants. It induced HR in Arabidopsis, a dicotyledonous model plant, including the oxidative burst and cell death. We investigated defense signal transduction activated by PA through marker genes of particular defense pathways in Arabidopsis. The result indicated that both the salicylic acid-dependent and jasmonic acid/ethylene-dependent pathways were activated by PA, in which the marker defense genes PR-1, PR-2 and PDF 1.2 were all induced in dose-dependent and time-course manners. We also observed that the PAinduced reactive oxygen species (ROS) production in rice suspension cells was Ca2+-dependent. Together with our previous studies of PA-induced defense activation in rice, we conclude that PA acts as a nonspecific elicitor in plant defense and has a potential utilization in cellular model establishment of systemicac quired resistance (SAR) activation.

  11. Modulation of phenytoin teratogenicity and embryonic covalent binding by acetylsalicylic acid, caffeic acid, and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Wells, P.G.; Zubovits, J.T.; Wong, S.T.; Molinari, L.M.; Ali, S.

    1989-02-01

    Teratogenicity of the anticonvulsant drug phenytoin is thought to involve its bioactivation by cytochromes P-450 to a reactive arene oxide intermediate. We hypothesized that phenytoin also may be bioactivated to a teratogenic free radical intermediate by another enzymatic system, prostaglandin synthetase. To evaluate the teratogenic contribution of this latter pathway, an irreversible inhibitor of prostaglandin synthetase, acetylsalicylic acid (ASA), 10 mg/kg intraperitoneally (ip), was administered to pregnant CD-1 mice at 9:00 AM on Gestational Days 12 and 13, 2 hr before phenytoin, 65 mg/kg ip. Other groups were pretreated 2 hr prior to phenytoin administration with either the antioxidant caffeic acid or the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). Caffeic acid and PBN were given ip in doses that respectively were up to 1.0 to 0.05 molar equivalents to the dose of phenytoin. Dams were killed on Day 19 and the fetuses were assessed for teratologic anomalies. A similar study evaluated the effect of ASA on the in vivo covalent binding of radiolabeled phenytoin administered on Day 12, in which case dams were killed 24 hr later on Day 13. ASA pretreatment produced a 50% reduction in the incidence of fetal cleft palates induced by phenytoin (p less than 0.05), without significantly altering the incidence of resorptions or mean fetal body weight. Pretreatment with either caffeic acid or PBN resulted in dose-related decreases in the incidence of fetal cleft palates produced by phenytoin, with maximal respective reductions of 71 and 82% at the highest doses of caffeic acid and PBN (p less than 0.05).

  12. Glucagon and cAMP inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene expression in human hepatocytes: discordant regulation of bile acid synthesis and gluconeogenesis.

    Science.gov (United States)

    Song, Kwang-Hoon; Chiang, John Y L

    2006-01-01

    The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated to control bile acid synthesis and maintain lipid homeostasis. Recent studies in mice suggest that bile acid synthesis is regulated by the fasted-to-fed cycle, and fasting induces CYP7A1 gene expression in parallel to the induction of peroxisome proliferators-activated receptor gamma co-activator 1alpha (PGC-1alpha) and phosphoenolpyruvate carboxykinase (PEPCK). How glucagon regulates CYP7A1 gene expression in the human liver is not clear. Here we show that glucagon and cyclic adenosine monophosphate (cAMP) strongly repressed CYP7A1 mRNA expression in human primary hepatocytes. Reporter assays confirmed that cAMP and protein kinase A (PKA) inhibited human CYP7A1 gene transcription, in contrast to their stimulation of the PEPCK gene. Mutagenesis analysis identified a PKA-responsive region located within the previously identified HNF4alpha binding site in the human CYP7A1 promoter. Glucagon and cAMP increased HNF4alpha phosphorylation and reduced the amount of HNF4alpha present in CYP7A1 chromatin. Our findings suggest that glucagon inhibited CYP7A1 gene expression via PKA phosphorylation of HNF4alpha, which lost its ability to bind the CYP7A1 gene and resulted in inhibition of human CYP7A1 gene transcription. In conclusion, this study unveils a species difference in nutrient regulation of the human and mouse CYP7A1 gene and suggests a discordant regulation of bile acid synthesis and gluconeogenesis by glucagon in human livers during fasting.

  13. Reduction of Burn Progression with Topical Delivery of (Antitumor Necrosis Factor-alpha )-Hyaluronic Acid Conjugates

    Science.gov (United States)

    2012-01-01

    level of hair follicle cell apoptosis within 24 hours of the initial burn injury.27 Intravenous injection of semapimod, a selective inhibitor of...effect of such treat- ment was unclear. Singer and coworkers have also demonstrated 30% reduction in depth of hair follicle necrosis after systemic...whether topical application of antibodies targeting tumor necrosis factor-a (TNF-a) or interleukin-6 (IL-6) conjugated to hyaluronic acid (HA) could

  14. Identification of the catalytic residues of alpha-amino acid ester hydrolase from Acetobacter turbidans by labeling and site-directed mutagenesis

    NARCIS (Netherlands)

    Polderman - Tijmes, Jolanda j.; Jekel, Peter A.; Jeronimus-Stratingh, CM; Bruins, Andries P.; van der Laan, Jan-Metske; Sonke, Theo; Janssen, Dick B.

    2002-01-01

    The alpha-amino acid ester hydrolase from Acetobacter turbidans ATCC 9325 is capable of hydrolyzing and synthesizing the side chain peptide bond in beta-lactam antibiotics. Data base searches revealed that the enzyme contains an active site serine consensus sequence Gly-X-Ser-Tyr-X-Gly that is also

  15. Microencapsulation of H. pluvialis oleoresins with different fatty acid composition: Kinetic stability of astaxanthin and alpha-tocopherol.

    Science.gov (United States)

    Bustamante, Andrés; Masson, Lilia; Velasco, Joaquín; del Valle, José Manuel; Robert, Paz

    2016-01-01

    Haematococcus pluvialis is a natural source of astaxanthin (AX). However, AX loses its natural protection when extracted from this microalga. In this study, a supercritical fluid extract (SFE) of H. pluvialis was obtained and added to oils with different fatty acid compositions (sunflower oil (SO) or high oleic sunflower oil (HOSO)). The oleoresins of H. pluvialis ((SO+SFE) and (HOSO+SFE)) were encapsulated with Capsul by spray drying. The stability of the oleoresins and powders were studied at 40, 50 and 70° C. AX and alpha-tocopherol (AT) degradation followed a zero-order and first-order kinetic model, respectively, for all systems. The encapsulation of oleoresins improved the stability of AX and AT to a greater extent in oleoresins with a monounsaturated fatty acid profile, as shown by the significantly lowest degradation rate constants and longest half-lives. Therefore, the encapsulation of H. pluvialis oleoresins is an alternative to developing a functional ingredient for healthy food design.

  16. Chrysophanic Acid Suppresses Adipogenesis and Induces Thermogenesis by Activating AMP-activated Protein Kinase Alpha in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Hara Lim

    2016-12-01

    Full Text Available Chrysophanic acid (CA is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA. CA reduced weight gain in HFD-induced obese mice. They also decreased lipid accumulation and the expressions of adipogenesis factors including peroxisome proliferator-activated receptor gamma (PPARγ and CCAAT/enhancer-binding protein alpha (C/EBPα in 3T3-L1 adipocytes. In addition, uncoupling protein 1 (UCP1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α, the brown fat specific thermogenic genes, were up-regulated in brown adipocytes by CA treatment. Furthermore, when co-treated with Compound C, the AMP-activated protein kinase (AMPK inhibitor, CA was able to restore the activation of AMPKα in both types of adipocytes, indicating the multi-controlling effect of CA was partially via the AMPKα pathway. Given all together, these results indicate that CA can ameliorate obesity by controlling the adipogenic and thermogenic pathway at the same time. On these bases we suggest the new potential of CA as an anti-obese pharmacotherapy.

  17. Activation of retinoic acid receptor alpha is sufficient for full induction of retinoid responses in SK-BR-3 and T47D human breast cancer cells.

    Science.gov (United States)

    Schneider, S M; Offterdinger, M; Huber, H; Grunt, T W

    2000-10-01

    Retinoid signaling via retinoic acid (RA) and retinoid X receptors (RARs and RXRs) regulates mammary epithelial cell growth and differentiation. Loss of RAR-beta might represent an early event during breast carcinogenesis. Higher differentiated, estrogen-dependent, estrogen receptor (ER)-positive (ER+) mammary carcinoma cells have been found to contain relatively high levels of RAR-alpha and to be responsive to retinoids, whereas most undifferentiated, estrogen-independent, ER-negative (ER-) cells are characterized by low RAR-alpha expression and by retinoid resistance. In contrast, RAR-gamma is detectable at equal levels in both ER+ and ER- cells. In the present investigation, we directly examined the relative contribution of the distinct retinoid receptors to the retinoid response of breast cancer cells by comparing the effects of low concentrations of specific retinoids, which selectively activate individual receptor subtypes, on growth, cell cycle distribution, apoptosis, and on the autoregulation of RAR-alpha and RAR-gamma in ER- SK-BR-3 and ER+ T47D breast cancer cells. In vitro growth activity was determined by using a colorimetric cell viability assay and analysis of cell cycle distribution, and apoptosis was performed by flow cytometry of propidium iodide-stained or fluorescent Annexin V-labeled cells, respectively, whereas expression of RAR-alpha and RAR-gamma was determined by Northern blotting. Both cell lines are retinoid sensitive and express high amounts of RAR-alpha, RAR-gamma, and RXR-alpha. RAR-alpha-selective compounds (AM80 and AM580) inhibit cell growth, induce G1 arrest, stimulate apoptosis, and up-regulate RAR-alpha and RAR-gamma mRNA as efficiently as RAR/RXR-pan-reactive (9-cis RA) and RAR-pan-reactive retinoids (all-trans RA, TTNPB). Remarkably, an RAR-alpha antagonist (Ro 41-5253) not only blocks the RAR-alpha-selective agonists but also the pan-reactive compounds. In contrast, RAR-13-selective (CD417), RAR-gamma-selective (CD437/AHPN

  18. Effect of capric, lauric and alpha-linolenic acids on the division time distributions of single cells of Staphylococcus aureus.

    Science.gov (United States)

    Sado Kamdem, S; Guerzoni, M E; Baranyi, J; Pin, C

    2008-11-30

    The effect of non-inhibitory concentrations of capric, lauric and alpha-linolenic acids (C10:0, C12:0 and C18:3 respectively) on the division time distribution of single cells of Staphylococcus aureus was evaluated at pH 7 and pH 5. The effect of the initial cell concentration on the lag time of growing cell populations was also assessed. The statistical properties of the division times (defined as the time interval from birth to next binary fission for a single cell) were studied using the method of Elfwing et al. [Elfwing, A., Le Marc, Y., Baranyi, J., Ballagi, A., 2004. Observing the growth and division of large number of individual bacteria using image analysis. Applied and Environmental Microbiology 70, 675-678]. The division times were significantly longer in the presence of free fatty acids than in the control. Shorter division intervals were detected at pH 7 than at pH 5 in the control experiment and in the presence of C10:0. However, both C12:0 and C18:3 slowed down the growth, regardless of the pH. The observed division time distributions were used to simulate growth curves from different inoculum sizes using the stochastic birth process described by Pin and Baranyi [Pin, C., Baranyi, J., 2006. Kinetics of single cells: observation and modelling of a stochastic process. Applied and Environmental Microbiology 72, 2163-2169]. The output of the simulation results were compared with observed data. The lag times fitted to simulated growth curves were in good agreement with those fitted to growth curves measured by plate counts. The averaged out effect of the population masked the effect of the free fatty acids and pH on the division times of single cells.

  19. Ubiquitin/proteasome pathway regulates levels of retinoic acid receptor gamma and retinoid X receptor alpha in human keratinocytes.

    Science.gov (United States)

    Boudjelal, M; Wang, Z; Voorhees, J J; Fisher, G J

    2000-04-15

    Repeated exposure of human skin to solar UV radiation leads to premature aging (photoaging) and skin cancer. UV-induced skin damage can be ameliorated by all-trans retinoic acid treatment. The actions of retinoic acid in skin keratinocytes are mediated primarily by nuclear retinoic acid receptor gamma (RARgamma) and retinoid X receptor alpha (RXRalpha). We found that exposure of cultured primary human keratinocytes to UV irradiation (30 mJ/cm2) substantially reduced (50-90%) RARgamma and RXRalpha mRNA and protein within 8 h. The rates of disappearance of RARgamma and RXRalpha proteins after UV exposure or treatment with the protein synthesis inhibitor cycloheximide were similar. UV irradiation did not increase the rate of breakdown of RARgamma or RXRalpha but rather reduced their rate of synthesis. The addition of proteasome inhibitors MG132 and LLvL, but not the lysosomal inhibitor E64, prevented loss of RARgamma and RXRalpha proteins after exposure of keratinocytes to either UV radiation or cycloheximide. Soluble extracts from nonirradiated or UV-irradiated keratinocytes possessed similar levels of proteasome activity that degraded RARgamma and RXRalpha proteins in vitro. Furthermore, RARgamma and RXRalpha were polyubiquitinated in intact cells. RXRalpha was found to contain two proline, glutamate/aspartate, serine, and threonine (PEST) motifs, which confer rapid turnover of many short-lived regulatory proteins that are degraded by the ubiquitin/proteasome pathway. However, the PEST motifs in RXRalpha did not function to regulate its stability, because deletion of the PEST motifs individually or together did not alter ubiquitination or proteasome-mediated degradation of RXRalpha. These results demonstrate that loss of RARgamma and RXRalpha proteins after UV irradiation results from degradation via the ubiquitin/proteasome pathway. Taken together, the data here indicate that ubiquitin/proteasome-mediated breakdown is an important mechanism regulating the levels of

  20. Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha.

    Science.gov (United States)

    Tsai, Chin-Shaw Stella; Luo, Shue-Fen; Ning, Chung-Chu; Lin, Chien-Liang; Jiang, Ming-Chung; Liao, Ching-Fong

    2009-08-01

    Epidemiological studies indicate that acetylsalicylic acid may reduce the risk of mortality due to colon cancers. Metastasis is the major cause of cancer death. Matrix metalloproteinases (MMPs) play important roles in tumor invasion regulation, and prostaglandin F(2)alpha (PGF(2)alpha) is a key stimulator of MMP production. Thus, we investigated whether acetylsalicylic acid regulated MMP activity and the invasion of cancer cells and whether PGF(2)alpha attenuated acetylsalicylic acid-inhibited invasion of cancer cells. Gelatin-based zymography assays showed that acetylsalicylic acid inhibited the MMP-2 activity of B16F0 melanoma cells. Matrigel-based chemoinvasion assays showed that acetylsalicylic acid inhibited the invasion of B16F0 cells. Acetylsalicylic acid can inhibit PGF(2)alpha synthesis and PGF(2)alpha is a key stimulator of MMP-2 production. Our data showed that PGF(2)alpha treatment attenuated the acetylsalicylic acid-inhibited invasion of B16F0 cells. In animal experiments, acetylsalicylic acid reduced colorectal metastasis of B16F0 cells in C57BL/6J mice by 44%. Our results suggest that PGF(2)alpha is a therapeutic target for metastasis inhibition and acetylsalicylic acid may possess anti-metastasis ability.

  1. Low dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid is associated with increased inflammatory and oxidative stress status in a Swedish cohort.

    Science.gov (United States)

    Helmersson, Johanna; Arnlöv, Johan; Larsson, Anders; Basu, Samar

    2009-06-01

    Fruit and vegetable consumption has been associated with a reduced risk of several diseases including CVD. A part of these effects seen could be linked to anti-inflammatory and antioxidative effects, although this has not been thoroughly investigated. The present study was designed to investigate the effects of the dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid on in vivo biomarkers of inflammation (PGF2alpha, high-sensitive C-reactive protein (hsCRP) and IL-6 formation) and oxidative stress (F2-isoprostane formation), the two important factors associated with accelerated atherosclerosis. The dietary intake of 704 participants in the Uppsala Longitudinal Study of Adult Men (ULSAM) at age 70 years was registered and inflammatory and oxidative stress biomarkers were quantified 7 years later. The registered dietary intakes of ascorbic acid and alpha-tocopherol were negatively associated linearly and in quartiles with both PGF2alpha, hsCRP, IL-6 and F2-isoprostanes, where ascorbic acid intake generally was more strongly associated. Dietary intake of beta-carotene was only significantly negatively associated with F2-isoprostanes. In conclusion, the present study is the first to suggest that the intake of food rich in antioxidants is associated with reduced cyclo-oxygenase- and cytokine-mediated inflammation and oxidative stress at 7 years of follow-up. These associations could be linked to the beneficial effects of fruit and vegetables observed on CVD.

  2. Simultaneous determination of alpha-aminoadipic semialdehyde, piperideine-6-carboxylate and pipecolic acid by LC-MS/MS for pyridoxine-dependent seizures and folinic acid-responsive seizures.

    Science.gov (United States)

    Sadilkova, Katerina; Gospe, Sidney M; Hahn, Si Houn

    2009-10-30

    Pyridoxine-dependent seizures (PDS) is an autosomal recessive disorder characterized by seizures presenting in neonates or infants up to 3 years of age which respond to pharmacological doses of pyridoxine. Alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) deficiency was identified as an underlying defect in PDS characterized by accumulation of alpha-aminoadipic semialdehyde (alpha-AASA) as a specific marker and recently folinic acid-responsive seizures (FRS) were found to be allelic to PDS as the putative mutations were identified in the antiquitin gene (ALDH7A1). alpha-AASA is known to be in reversible equilibrium with its cyclic Shiff base, delta(1)-piperideine-6-carboxylate (P6C). Pipecolic acid (PA) is another biomarker often elevated but is not specific to PDS. Here, we developed the liquid chromatography-mass spectrometry (LC-MS/MS) method to determine the analytes of alpha-AASA, P6C and PA simultaneously in plasma and validated the assay using samples from confirmed cases. This approach eliminates the extra time and expense of running multiple assays and provides valuable information for the rapid diagnosis and treatment of patients with PDS and FRS which potentially could lead to a better outcome with improved quality of life. The stability study showed that alpha-AASA and P6C were unstable even at -20 degrees C. A careful sample handling with immediate freezing and testing is required for reliable result.

  3. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    Directory of Open Access Journals (Sweden)

    Liu Suling

    2008-07-01

    Full Text Available Abstract Background Conjugated linoleic acid (CLA, a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. Methods The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. Results The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E2 stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA

  4. Functional bread with n-3 alpha linolenic acid from whole chia (Salvia hispanica L.) flour.

    Science.gov (United States)

    Luna Pizarro, Patricia; Almeida, Eveline Lopes; Coelho, Alessandra Silva; Sammán, Norma Cristina; Hubinger, Miriam Dupas; Chang, Yoon Kil

    2015-07-01

    This work proposed to study the effects of the addition of whole chia flour (WCF) on the technological, nutritional and sensory qualities of bread. Different WCF contents (0 and 20 %) and vital gluten (VG) (0 and 4 %) were added to bread according to a 2(2) central composite rotational design. WCF decreased the specific volume, lightness and hue angle of the bread loaves, but did not affect the chroma values. WCF and VG contributed to maintenance of the moisture content of the loaves during the storage period. The increased firmness found with the addition of high levels of WCF (more than 10 %) was countered by larger amounts of VG (more than 2 %). The optimum loaf (10 % WCF and 2 % VG) showed 26 % more lipids, 19 % more protein and 11 % more ash than the standard loaf (0 % WCF and 0 % VG). A better lipid profile was also found (higher omega-3 fatty acid content and a better omega-6/omega-3 ratio). Both breads were positively rated in the sensory profile analysis.

  5. Asaia krungthepensis sp. nov., an acetic acid bacterium in the alpha-Proteobacteria.

    Science.gov (United States)

    Yukphan, Pattaraporn; Potacharoen, Wanchern; Tanasupawat, Somboon; Tanticharoen, Morakot; Yamada, Yuzo

    2004-03-01

    Three bacterial strains were isolated from flowers collected in Bangkok, Thailand, by an enrichment-culture approach for acetic acid bacteria. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolates were located in the lineage of the genus Asaia but constituted a cluster separate from the type strains of Asaia bogorensis and Asaia siamensis. The DNA base composition of the isolates was 60.2-60.5 mol% G+C, with a range of 0.3 mol%. The isolates constituted a taxon separate from Asaia bogorensis and Asaia siamensis on the basis of DNA-DNA relatedness. The isolates had morphological, physiological, biochemical and chemotaxonomic characteristics similar to those of the type strains of Asaia bogorensis and Asaia siamensis, but the isolates grew on maltose. The major ubiquinone was Q(10). On the basis of the results obtained, the name Asaia krungthepensis sp. nov. is proposed for the isolates. The type strain is isolate AA08(T) (=BCC 12978(T)=TISTR 1524(T)=NBRC 100057(T)=NRIC 0535(T)), which had a DNA G+C content of 60.3 mol% and was isolated from a heliconia flower ('paksaasawan' in Thai; Heliconia sp.) collected in Bangkok, Thailand.

  6. Metal selectivity of Sargassum spp. and their alginates in relation to their alpha-L-guluronic acid content and conformation.

    Science.gov (United States)

    Davis, Thomas A; Llanes, Francisco; Volesky, Bohumil; Mucci, Alfonso

    2003-01-15

    The discovery of a consistent and unusual enrichment in homopolymeric alpha-L-guluronic acid G-blocks in alginates extracted from a suite of Sargassum brown algae is described in this study. 1H NMR spectroscopy was used to characterize these alginates which display homopolymeric guluronic acid block (G-block) frequency values (F(GG)) between 0.37 and 0.81. The presence of these G-blocks results in an enhanced selectivity for cadmium or calcium relative to monovalent ions such as sodium and the proton as well as smaller divalent ions such as magnesium. Results of competitive exchange experiments for the Cd-Ca-alginate system yield selectivity coefficient, K*(Cd)Ca, values between 0.43 +/- 0.10 and 1.32 +/- 0.02 for a range in F(GG) of 0.23 to 0.81. In contrast to the Cd-Ca-alginate system, the Mg-Ca-alginate and Mg-Cd-alginate systems yielded maximum values of K*(Mg)Ca (18.0 +/- 1.4) and K*(Mg)Cd (16.0 +/- 0.9) for the alginates extracted from Sargassum fluitans (F(GG) = 0.81; Cuba) and Sargassum thunbergii (F(GG) = 0.75; Korea), respectively. Selectivity studies with mixed-metal pair alginate systems highlight the importance of the specific macromolecular conformation of the alginate polymer in determining metal binding behavior in multiple-metal systems. Furthermore, they demonstrate the importance of the conformation of the alginate as it occurs within the tissue of Sargassum in determining the metal binding behavior of this algal biosorbent. The unique composition of the alginates present in species of Sargassum may represent a distinct advantage over other brown algal species when considering their implementation for the strategic removal of toxic heavy metals from contaminated and industrial wastewaters.

  7. Developmental Effects of Perfluorononanoic Acid in the Mouse Are Dependent on Peroxisome Proliferator-Activated Receptor-Alpha

    Directory of Open Access Journals (Sweden)

    Cynthia J. Wolf

    2010-01-01

    Full Text Available Perfluorononanoic acid (PFNA is one of the perfluoroalkyl acids found in the environment and in tissues of humans and wildlife. Prenatal exposure to PFNA negatively impacts survival and development of mice and activates the mouse and human peroxisome proliferator-activated receptor-alpha (PPAR. In the current study, we used PPAR knockout (KO and 129S1/SvlmJ wild-type (WT mice to investigate the role of PPAR in mediating PFNA-induced in vivo effects. Pregnant KO and WT mice were dosed orally with water (vehicle control: 10 ml/kg, 0.83, 1.1, 1.5, or 2 mg/kg PFNA on gestational days (GDs 1–18 (day of sperm plug = GD 0. Maternal weight gain, implantation, litter size, and pup weight at birth were unaffected in either strain. PFNA exposure reduced the number of live pups at birth and survival of offspring to weaning in the 1.1 and 2 mg/kg groups in WT. Eye opening was delayed (mean delay 2.1 days and pup weight at weaning was reduced in WT pups at 2 mg/kg. These developmental endpoints were not affected in the KO. Relative liver weight was increased in a dose-dependent manner in dams and pups of the WT strain at all dose levels but only slightly increased in the highest dose group in the KO strain. In summary, PFNA altered liver weight of dams and pups, pup survival, body weight, and development in the WT, while only inducing a slight increase in relative liver weight of dams and pups at 2 mg/kg in KO mice. These results suggest that PPAR is an essential mediator of PFNA-induced developmental toxicity in the mouse.

  8. Cleft lip with or without cleft palate: Associations with transforming growth factor alpha and retinoic acid receptor loci

    Energy Technology Data Exchange (ETDEWEB)

    Chenevix-Trench, G.; Jones, K. (Queensland Inst. of Medical Research (Australia) Univ. of Queensland (Australia)); Green, A.C.; Duffy, D.L.; Martin, N.G. (Queensland Inst. of Medical Research (Australia))

    1992-12-01

    The first association study of cleft lip with or without cleft palate (CL/P), with candidate genes, found an association with the transforming growth-factor alpha (TGFA) locus. This finding has since been replicated, in whole or in part, in three independent studies. Here the authors extend their original analysis of the TGFA TaqI RFLP to two other TGFA RFLPs and seven other RFLPs at five candidate genes in 117 nonsyndromic cases of CL/P and 113 controls. The other candidate genes were the retinoic acid receptor (RARA), the bcl-2 oncogene, and the homeobox genes 2F, 2G, and EN2. Significant associations with the TGFA TaqI and BamHI RFLPs were confirmed, although associations of clefting with previously reported haplotypes did not reach significance. Of particular interest, in view of the known teratogenic role of retinoic acid, was a significant association with the RARA PstI RFLP (P = .016; not corrected for multiple testing). The effect on risk of the A2 allele appears to be additive, and although the A2A2 homozygote only has an odds ratio of about 2 and recurrence risk to first-degree relatives ([lambda][sub 1]) of 1.06, because it is so common it may account for as much as a third of the attributable risk of clefting. There is no evidence of interaction between the TGFA and RARA polymorphisms on risk, and jointly they appear to account for almost half the attributable risk of clefting. 43 refs., 1 fig., 4 tabs.

  9. The Roles of Alpha-Momorcharin and Jasmonic Acid in Modulating the Response of Momordica charantia to Cucumber Mosaic Virus.

    Science.gov (United States)

    Yang, Ting; Meng, Yao; Chen, Li-Juan; Lin, Hong-Hui; Xi, De-Hui

    2016-01-01

    Alpha-momorcharin (α-MMC) is a type-I ribosome inactivating protein with a molecular weight of 29 kDa that is found in Momordica charantia, and has been shown to be effective against a broad range of human viruses as well as having anti-tumor activities. However, the role of endogenous α-MMC under viral infection and the mechanism of the anti-viral activities of α-MMC in plants are still unknown. To study the effect of α-MMC on plant viral defense and how α-MMC increases plant resistance to virus, the M. charantia-cucumber mosaic virus (CMV) interaction system was investigated. The results showed that the α-MMC level was positively correlated with the resistance of M. charantia to CMV. α-MMC treatment could alleviate photosystem damage and enhance the ratio of glutathione/glutathione disulfide in M. charantia under CMV infection. The relationship of α-MMC and defense related phytohormones, and their roles in plant defense were further investigated. α-MMC treatment led to a significant increase of jasmonic acid (JA) and vice versa, while there was no obvious relevance between salicylic acid and α-MMC. In addition, reactive oxygen species (ROS) were induced in α-MMC-pretreated plants, in a similar way to the ROS burst in JA-pretreated plants. The production of ROS in both ibuprofen (JA inhibitor) and (α-MMC+ibuprofen)-pretreated plants was reduced markedly, leading to a greater susceptibility of M. charantia to CMV. Our results indicate that the anti-viral activities of α-MMC in M. charantia may be accomplished through the JA related signaling pathway.

  10. The roles of alpha-momorcharin and jasmonic acid in modulating the response of Momordica charantia to Cucumber mosaic virus

    Directory of Open Access Journals (Sweden)

    Ting Yang

    2016-11-01

    Full Text Available Alpha-momorcharin (α-MMC is a type-I ribosome inactivating protein (RIP with a molecular weight of 29kDa that is found in Momordica charantia, and has been shown to be effective against a broad range of human viruses as well as having anti-tumor activities. However, the role of endogenous α-MMC under viral infection and the mechanism of the anti-viral activities of α-MMC in plants are still unknown. To study the effect of α-MMC on plant viral defense and how α-MMC increases plant resistance to virus, the M. charantia–cucumber mosaic virus (CMV interaction system was investigated. The results showed that the α-MMC level was positively correlated with the resistance of M. charantia to CMV. α-MMC treatment could alleviate photosystem damage and enhance the ratio of glutathione/glutathione disulfide (GSH/GSSH in M. charantia under CMV infection. The relationship of α-MMC and defense related phytohormones, and their roles in plant defense were further investigated. α-MMC treatment led to a significant increase of jasmonic acid (JA and vice versa, while there was no obvious relevance between salicylic acid (SA and α-MMC. In addition, reactive oxygen species (ROS were induced in α-MMC-pretreated plants, in a similar way to the ROS burst in JA-pretreated plants. The production of ROS in both ibuprofen (JA inhibitor and (α-MMC+ibuprofen-pretreated plants was reduced markedly, leading to a greater susceptibility of M. charantia to CMV. Our results indicate that the anti-viral activities of α-MMC in M. charantia may be accomplished through the JA related signaling pathway.

  11. alpha1-acid glycoprotein as a putative biomarker for monitoring the development of the type II reactional stage of leprosy.

    Science.gov (United States)

    Gupta, Nishma; Shankernarayan, Nallakandy P; Dharmalingam, Kuppamuthu

    2010-04-01

    Leprosy, a spectral disease manifested on the basis of host immune responses, is complicated by its reactional stages, namely type I reversal reaction (RR) and type II erythema nodosum leprosum (ENL). These reactional stages are characterized by uncontrolled and aberrant immune responses. Biomarkers for reactional stages would aid in early diagnosis, efficient treatment, prevention of neurological complications and prediction of predisposition to reactional stages. In this study, comparative analysis of the serum proteome of leprosy patients by two-dimensional electrophoresis (2DE) followed by mass spectrometry showed differential expression of acute-phase protein alpha (1)-acid glycoprotein (AGP; also known as orosomucoid). AGP levels in untreated ENL cases were significantly higher than in lepromatous leprosy (LL; a non-reactional disease stage) (P=0.0126), RR (P=0.0176) and healthy controls (P=0.0030). These data were confirmed using ELISA. The levels of AGP decreased to normal levels after treatment with multidrug therapy and thalidomide (P =0.0167). In a follow-up study, AGP levels, which were high in the untreated ENL stage, decreased significantly at 5 days ( P=0.0084) and 21 days (P=0.0027) post-treatment. A stage-dependent increase in AGP in an LL patient who progressed into the ENL stage was also shown. Glycosylation analysis by 2DE showed differential expression of acidic glycoforms of AGP in untreated ENL cases. Changes in AGP concentration and differential expression of isoforms correlated with the inflammatory condition in ENL and also with the treatment regimen. Thus, initial validation of AGP as an ENL-specific biomarker and treatment indicator was shown in this study.

  12. Determination of human serum alpha1-acid glycoprotein and albumin binding of various marketed and preclinical kinase inhibitors.

    Science.gov (United States)

    Zsila, Ferenc; Fitos, Ilona; Bencze, Gyula; Kéri, György; Orfi, László

    2009-01-01

    There are about 380 protein kinase inhibitors in drug development as of today and 15 drugs have been marketed already for the treatment of cancer. This time 139 validated kinase targets are in the focus of drug research of pharmaceutical companies and big efforts are made for the development of new, druglike kinase inhibitors. Plasma protein binding is an important factor of the ADME profiling of a drug compound. Human serum albumin (HSA) and alpha(1)-acid glycoprotein (AAG) are the most relevant drug carriers in blood plasma. Since previous literature data indicated that AAG is the principal plasma binding component of some kinase inhibitors the present work focuses on the comprehensive evaluation of AAG binding of a series of marketed and experimental kinase inhibitors by using circular dichroism (CD) spectroscopy approach. HSA binding was also evaluated by affinity chromatography. Protein binding interactions of twenty-six kinase inhibitors are characterized. The contribution of AAG and HSA binding data to the pharmacokinetic profiles of the investigated therapeutic agents is discussed. Structural, biological and drug binding properties of AAG as well as the applicability of the CD method in studying drug-protein binding interactions are also briefly reviewed.

  13. Exercise-induced muscle damage is not attenuated by beta-hydroxy-beta-methylbutyrate and alpha-ketoisocaproic acid supplementation.

    Science.gov (United States)

    Nunan, David; Howatson, Glyn; van Someren, Ken A

    2010-02-01

    The purpose of this study was to examine the effects of combined oral beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproic acid (KIC) supplementation on indices of exercise-induced muscle damage (EIMD) after an acute bout of eccentric-biased exercise. Fourteen male subjects were allocated to 2 groups: a placebo group (3 g.d corn flour, N = 7) or an HMB + KIC group (3 g.d HMB and 0.3 g.d KIC, N = 7). Supplementation commenced 11 days before a 40-minute bout of downhill running and continued for 3 days post-exercise. Delayed-onset muscle soreness, mid-thigh girth, knee extensor range of motion, serum creatine kinase (CK) activity, and isometric and concentric torque were assessed pre-exercise and at 24, 48, and 72 hours post-exercise. Delayed-onset muscle soreness, CK activity, and isometric and concentric torque all changed over the 72-hour period (p < 0.05); however, HMB + KIC had no significant effect on any of the indices of muscle damage. Although 14 days HMB and KIC supplementation did not attenuate indices of EIMD after an acute bout of unaccustomed eccentric-biased exercise, there was a trend for a more rapid rate of recovery in isometric and isokinetic muscle function. beta-hydroxy-beta-methylbutyrate and KIC may therefore provide limited benefit in the recovery of muscle function after EIMD in untrained subjects or after unaccustomed exercise.

  14. Singlet oxygen generation from the decomposition of alpha-linolenic acid hydroperoxide by cytochrome c and lactoperoxidase.

    Science.gov (United States)

    Sun, Shuna; Bao, Zhijuan; Ma, Huimin; Zhang, Deqing; Zheng, Xiaoping

    2007-06-01

    Generation of singlet oxygen is first investigated in the decomposition of polyunsaturated lipid peroxide, alpha-linolenic acid hydroperoxide (LAOOH), by heme-proteins such as cytochrome c and lactoperoxidase. Chemiluminescence and electron spin resonance methods are used to confirm the singlet oxygen generation and quantify its yield. Decomposition products of LAOOH are characterized by HPLC-ESI-MS, which suggests that singlet oxygen is produced via the decomposition of a linear tetraoxide intermediate (Russell's mechanism). Free radicals formed in the decomposition are also identified by the electron spin resonance technique, and the results show that peroxyl, alkyl, and epoxyalkyl radicals are involved. The changes of cytochrome c and lactoperoxidase in the reaction are monitored by UV-visible spectroscopy, revealing the action of a monoelectronic and two-electronic oxidation for cytochrome c and lactoperoxidase, respectively. These results suggest that cytochrome c causes a homolytic reaction of LAOOH, generating alkoxyl radical and then peroxyl radical, which in turn releases singlet oxygen following the Russell mechanism, whereas lactoperoxidase leads to a heterolytic reaction of LAOOH, and the resulting ferryl porphyryl radical of lactoperoxidase abstracts the hydrogen atom from LAOOH to give peroxyl radical and then singlet oxygen. This observation would be important for a better understanding of the damage mechanism of cell membrane or lipoprotein by singlet oxygen and various radicals generated in the peroxidation and decomposition of lipids induced by heme-proteins.

  15. Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and alpha2-adrenoceptor gene expression in hippocampus.

    Science.gov (United States)

    Alonso, Elba; Garrido, Elisa; Díez-Fernández, Carmen; Pérez-García, Carmen; Herradón, Gonzalo; Ezquerra, Laura; Deuel, Thomas F; Alguacil, Luis F

    2007-01-29

    The alpha(2)-adrenoceptor antagonist yohimbine is known to oppose to several pharmacological effects of opioid drugs, but the consequences and the mechanisms involved remain to be clearly established. In the present study we have checked the effects of yohimbine on morphine-induced alterations of the expression of key proteins (glial fibrillary acidic protein, GFAP) and genes (alpha(2)-adrenoceptors) in rat brain areas known to be relevant in opioid dependence, addiction and individual vulnerability to drug abuse. Rats were treated with morphine in the presence or absence of yohimbine. The effects of the treatments on GFAP expression were studied by immunohistochemical staining in Locus Coeruleus (LC) and Nucleus of the Solitary Tract (NST), two important noradrenergic nuclei. In addition, drug effects on alpha(2)-adrenoceptor gene expression were determined by real time RT-PCR in the hippocampus, a brain area that receives noradrenergic input from the brainstem. Morphine administration increased GFAP expression both in LC and NST as it was previously reported in other brain areas. Yohimbine was found to efficiently prevent morphine-induced GFAP upregulation. Chronic (but not acute) morphine downregulated mRNA levels of alpha(2A)- and alpha(2C)-adrenoceptors in the hippocampus, while simultaneously increased the expression of the alpha(2B)-adrenoceptor gene. Again, yohimbine was able to prevent morphine-induced changes in the levels of expression of the three alpha(2)-adrenoceptor genes. These results correlate the well-established reduction of opioid dependence and addiction by yohimbine and suggest that this drug could interfere with the neural plasticity induced by chronic morphine in central noradrenergic pathways.

  16. Determination of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostan oic acid and 9 alpha,11 alpha-dihydroxy-15-oxo-2,3,4,5,20-pentanor-19-carboxyprostanoi c acid by gas chromatography/negative ion chemical ionization triple-stage quadrupole mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Schweer, H.; Meese, C.O.; Seyberth, H.W. (Universitaetskinderklinik, Heidelberg (Germany, F.R.))

    1990-08-15

    11 alpha-Hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic acid (PGE-M) and 9 alpha,11 alpha-dihydroxy-15-oxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid (PGF-M) in urine were determined in an isotope dilution assay by gas chromatography/triple-stage quadrupole mass spectrometry. After addition of the 2H7-labeled internal standard, O-methylhydroxylamine hydrochloride in acetate buffer was added either directly (PGE-M) or after standing overnight at pH 10 (PGF-M) to form the methoxime. The sample was acidified to pH 2.5 and PGE-M and PGF-M were extracted with ethyl acetate/hexane. Then the prostanoids were derivatized to the pentafluorobenzyl ester and purified by thin-layer chromatography and the trimethylsilyl ether was formed. The products were quantified by gas chromatography/triple-stage quadrupole mass spectrometry. For PGE-M, the fragment ions m/z 349 and m/z 356 (2H7 standard) (daughter ions of m/z 637 and m/z 644 (2H7 standard)) were used. The results of the PGE-M assay were compared with those of an assay using the (2H3)methoxime as the internal standard. For determination of PGF-M, the daughter ions m/z 484 and m/z 491 (2H7 standard) with the parent ions m/z 682 and m/z 689 (2H7 standard) were chosen.

  17. Non-covalent inclusion of ferulic acid with alpha-cyclodextrin improves photo-stability and delivery: NMR and modeling studies.

    Science.gov (United States)

    Anselmi, Cecilia; Centini, Marisanna; Maggiore, Maria; Gaggelli, Nicola; Andreassi, Marco; Buonocore, Anna; Beretta, Giangiacomo; Facino, Roberto Maffei

    2008-03-13

    Ferulic acid (FA) is a highly effective antioxidant and photo-protective agent, already approved in Japan as a sunscreen, but it is poorly suited for cosmetic application because of its low physicochemical stability. We prepared the inclusion complex of FA with alpha-cyclodextrin by co-precipitation from an aqueous solution, and used (1)H NMR and molecular dynamics to investigate the most probable structure of the inclusion complex. In rotating frame nuclear Overhouser effect spectroscopy (ROESY) experiments FA penetrated the alpha-CD hydrophobic cavity with the alpha,beta-unsaturated part of the molecule and some of its aromatic skeleton. In proton chemical shift measurements of FA and alpha-cyclodextrins we determined the stoichiometry of the association complex (1:1) by Job's method, and its stability constant (K(1:1) 1162+/-140 M(-1)) and described the molecular dynamics of the complex on the basis of theoretical studies. Encapsulation with alpha-cyclodextrin improves (i) the chemical stability of FA against UVB stress (10 MED [Minimal Erythemal Dose: 1 MED=25 mJ/cm(2) for skin phototype II: 30]), since no degradation products are formed after irradiation, and (ii) the bioavailability of FA on the skin, slowing its delivery (Strainer cell model).

  18. Composite poly-L-lactic acid/poly-({alpha},{beta})-DL-aspartic acid/collagen nanofibrous scaffolds for dermal tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Ravichandran, Rajeswari [Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Venugopal, Jayarama Reddy, E-mail: nnijrv@nus.edu.sg [Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Sundarrajan, Subramanian [Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Mukherjee, Shayanti [Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Sridhar, Radhakrishnan [Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Ramakrishna, Seeram, E-mail: seeram@nus.edu.sg [Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore)

    2012-08-01

    Tissue engineering scaffolds for skin tissue regeneration is an ever expounding area of research, as the products that meet the necessary requirements are far and elite. The nanofibrous poly-L-lactic acid/poly-({alpha},{beta})-DL-aspartic acid/Collagen (PLLA/PAA/Col I and III) scaffolds were fabricated by electrospinning and characterized by SEM, contact angle and FTIR analysis for skin tissue regeneration. The cell-scaffold interactions were analyzed by cell proliferation and their morphology observed in SEM. The results showed that the cell proliferation was significantly increased (p {<=} 0.05) in PLLA/PAA/Col I and III scaffolds compared to PLLA and PLLA/PAA nanofibrous scaffolds. The abundance and accessibility of adipose derived stem cells (ADSCs) may prove to be novel cell therapeutics for dermal tissue regeneration. The differentiation of ADSCs was confirmed using collagen expression and their morphology by CMFDA dye extrusion technique. The current study focuses on the application of PLLA/PAA/Col I and III nanofibrous scaffolds for skin tissue engineering and their potential use as substrate for the culture and differentiation of ADSCs. The objective for inclusion of a novel cell binding moiety like PAA was to replace damaged extracellular matrix and to guide new cells directly into the wound bed with enhanced proliferation and overall organization. This combinatorial epitome of PLLA/PAA/Col I and III nanofibrous scaffold with stem cell therapy to induce the necessary paracrine signalling effect would favour faster regeneration of the damaged skin tissues. - Highlights: Black-Right-Pointing-Pointer Differentiation of adipose derived stem cells in the presence of bFGF for wound healing Black-Right-Pointing-Pointer Introduction of PAA as ECM mimetic cell binding moiety Black-Right-Pointing-Pointer Combination of PLLA/PAA/Col I and III nanofibers and stem cell therapy for skin regeneration.

  19. Internode length in Pisum. Gene na may block gibberellin synthesis between ent-7. cap alpha. -hydroxykaurenoic acid and biggerellin A/sub 12/-aldehyde. [Pisum sativum

    Energy Technology Data Exchange (ETDEWEB)

    Ingram, T.J.; Reid, J.B.

    1987-04-01

    The elongation response of the gibberellin (GA) deficient genotypes na, ls, and lh of peas (Pisum sativum L.) to a range of GA-precursors was examined. Plants possessing gene na did not respond to precursors in the GA biosynthetic pathway prior to GA/sub 12/-aldehyde. In contrast, plants possessing lh and ls responded as well as wild-type plants (dwarfed with AMO-1618) to these compounds. The results suggest that GA biosynthesis is blocked prior to ent-kaurene in the lh and ls mutants and between ent-7..cap alpha..-hydroxykaurenoic acid and GA/sub 12/-aldehyde in the na mutant. Feeds of ent(/sup 3/H)kaurenoic acid and (/sup 2/H)GA/sub 12/-aldehyde to a range of genotypes supported the above conclusions. The na line WL1766 was shown by gas chromatography-mass spectrometry (GC-MS) to metabolize(/sup 2/H)GA/sub 12/-aldehyde to a number of (/sup 2/H)C/sub 19/-GAs including GA/sub 1/. However, there was no indication in na genotypes for the metabolism of ent-(/sup 3/H)kaurenoic acid to these GAs. In contrast, the expanding shoot tissue of all Na genotypes examined metabolized ent-(/sup 3/H)kaurenoic acid to radioactive compounds that co-chromatographed with GA/sub 1/, GA/sub 8/, GA/sub 20/, and GA/sub 29/. However, insufficient material was present for unequivocal identification of the metabolites. The radioactive profiles from HPLC of extracts of the node treated with ent-(/sup 3/H)kaurenoic acid were similar for both Na and na plants and contained ent-16..cap alpha..,17-dihydroxykaurenoic acid and ent-6..cap alpha..,7..cap alpha..,16..beta..,17-tetrahydroxykaurenoic acid (both characterized by GC-MS), suggesting that the metabolites arose from side branches of the main GA-biosynthetic pathway. Thus, both Na and na plants appear capable of ent-7..cap alpha..-hydroxylation.

  20. Acute effects of breakfasts containing alpha-lactalbumin, or gelatin with or without added tryptophan, on hunger, 'satiety' hormones and amino acid profiles.

    Science.gov (United States)

    Nieuwenhuizen, Arie G; Hochstenbach-Waelen, Ananda; Veldhorst, Margriet A B; Westerterp, Klaas R; Engelen, Mariëlle P K J; Brummer, Robert-Jan M; Deutz, Nicolaas E P; Westerterp-Plantenga, Margriet S

    2009-06-01

    Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat respectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in circulating total amino acids, GLP-1 and ghrelin.

  1. 银杏叶提取物、α-硫辛酸对糖尿病大鼠肾组织中糖基化终产物及其受体RAGE表达的影响%Extract of Ginkgo biloba and α-lipoic Acid Attenuate Advanced Glycation End Products Accumulation and RAGE Expression in Diabetic Nephropathy Rats

    Institute of Scientific and Technical Information of China (English)

    李雪竹; 严海东; 王俊; 江薇

    2011-01-01

    Objective To investigate the accumulation of advanced glycation end products (AGEs) and expression of receptor for AGEs (RAGE) in streptozocin (STZ)-induced diabetic nephropathy in rats, and the role of antioxidants on the AGEs-RAGE signaling.Methods Diabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg, and randomly divided into the DN group (n=12, treated with normal saline by intraperitoneal injection, once daily), the extract of Ginkgo biloba (EGb) group ( n =14, treated with EGb 300 mg/kg by oral administration, once every other day), and the α-lipoic add (ALA) group ( n =12, treated with ALA at the dose of 35 mg/kg by intraperitoneal injection, once every other day).Rats of the normal control group (n=10) were given vehicle dtrate buffer at the dose of 60 mg/kg.Rats were sacrificed at the 12th week and the 20th week of this study.The four groups were compared in terms of body weight, blood glucose, renal function, 24-h urine protein.Renal pathological changes were observed by PAS staining.Oxidative stress indices were detected using spectrophotometry.The concentrations of AGEs were measured using fluorospectrophotometry, and the expressions of RAGE were detected by Real-time PCR and Western blot.Results Compared with the normal control group, the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week.The pathological tissue staining showed dilated glomerular mesangium, proliferated glomerular matrix, vacuolar degeneration of the renal tubular epithelium.Malonaldehyde (MDA) levels and 8-hydroxide radical guanine deoxyriboside (8-OHdG) levels increased, and catalase (CAT) and reduced glutathione hormone (GSH) levels decreased.The AGEs contents in serum and renal tissue homogenate increased.The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week.The 24-h udne protein quantitation was reduced in the EGb group

  2. Mono-thioesters and di-thioesters by lipase-catalyzed reactions of alpha,omega-alkanedithiols with palmitic acid or its methyl ester.

    Science.gov (United States)

    Weber, N; Klein, E; Vosmann, K; Mukherjee, K D

    2004-06-01

    1- S-Mono-palmitoyl-hexanedithiol and 1- S-mono-palmitoyl-octanedithiol were prepared in high yield (80-90%) by solvent-free lipase-catalyzed thioesterification of palmitic acid with the corresponding alpha,omega-alkanedithiols in vacuo. Similarly, 1,6-di- S-palmitoyl-hexanedithiol and 1,8-di- S-palmitoyl-octanedithiol were prepared in moderate yield (50-60%) by solvent-free lipase-catalyzed thioesterification of palmitic acid with 1- S-Mono-palmitoyl-hexanedithiol and 1- S-mono-palmitoyl-octanedithiol, respectively. An immobilized lipase preparation from Rhizomucor miehei (Lipozyme RM IM) was more effective than a lipase B preparation from Candida antarctica (Novozym 435) or a lipase preparation from Thermomyces lanuginosus (Lipozyme TL IM). Lipase-catalyzed transthioesterifications of methyl palmitate with alpha,omega-alkanedithiols using the same enzymes were less effective than thioesterification for the preparation of the corresponding 1- S-mono-palmitoyl thioesters.

  3. A formal [3,3]-sigmatropic rearrangement route to quaternary alpha-vinyl amino acids: use of allylic N-PMP trifluoroacetimidates.

    Science.gov (United States)

    Berkowitz, David B; Wu, Bin; Li, Huijie

    2006-03-01

    Pd(II)-mediated rearrangement of allylic N-PMP (p-methoxyphenyl) trifluoroacetimidates provides the first formal sigmatropic route to quaternary, alpha-vinylic amino acids, potential suicide substrates for PLP enzymes. The amino acid side chains enter via transition-metal-mediated C-C bond constructions, including (i) Cu(I)-mediated conjugate addition (Ala); (ii) Pd(0)/AsPh3-mediated Stille coupling (allyl-Gly, Phe, DOPA, m-Tyr); and (iii) Pd(0)/Pt-Bu3-mediated Negishi coupling (Leu). In the synthesis of the DOPA decarboxylase inactivator, alpha-vinyl-m-tyrosine, the new N-PMP trifluoroacetimidate rearranges much more efficiently than the corresponding trichloroacetimidate.

  4. Host-mediated selection of influenza virus receptor variants. Sialic acid-alpha 2,6Gal-specific clones of A/duck/Ukraine/1/63 revert to sialic acid-alpha 2,3Gal-specific wild type in ovo.

    Science.gov (United States)

    Rogers, G N; Daniels, R S; Skehel, J J; Wiley, D C; Wang, X F; Higa, H H; Paulson, J C

    1985-06-25

    Human and animal influenza A isolates of the H3 serotype preferentially bind SA alpha 2,6Gal or SA alpha 2,3Gal linkages (where SA represents sialic acid), respectively, on cell-surface sialyloligosaccharides. Previously, we have demonstrated selection of SA alpha 2,3Gal-specific receptor variants of several human viruses which differed from the parent viruses by a single amino acid at residue 226 of the hemagglutinin which is located in the receptor binding pocket (Rogers, G. N., Paulson, J.C., Daniels, R.S., Skehel, J.J., Wilson, I.A., and Wiley, D.C. (1983) Nature 304, 76-78). In this report, the selection in the reverse direction was accomplished starting with a SA alpha 2,3Gal-specific avian virus, A/duck/Ukraine/1/63 (H3N7), yielding SA alpha 2,6Gal-specific variants that exhibit the receptor binding properties characteristic of the human isolates. Selection was again mediated at residue 226 of the hemagglutinin, in this case changing from Gln in the parent virus to Leu in the variants. Although the SA alpha 2,6Gal-specific avian virus variants were stable to passage in MDCK cells, they exhibited dramatic reversion to the SA alpha 2,3Gal-specific phenotype of the parent virus during a single passage in chicken embryos. This was in contrast to the SA alpha 2,6Gal-specific human virus isolates which were stable to passage in both hosts. The reversion of the avian virus variants in eggs provides compelling evidence for host-mediated selection of influenza virus receptor variants.

  5. aguA, the gene encoding an extracellular alpha-glucuronidase from Aspergillus tubingensis, is specifically induced on xylose and not on glucuronic acid.

    Science.gov (United States)

    de Vries, R P; Poulsen, C H; Madrid, S; Visser, J

    1998-01-01

    An extracellular alpha-glucuronidase was purified and characterized from a commercial Aspergillus preparation and from culture filtrate of Aspergillus tubingensis. The enzyme has a molecular mass of 107 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 112 kDa as determined by mass spectrometry, has a determined pI just below 5.2, and is stable at pH 6.0 for prolonged times. The pH optimum for the enzyme is between 4.5 and 6.0, and the temperature optimum is 70 degrees C. The alpha-glucuronidase is active mainly on small substituted xylo-oligomers but is also able to release a small amount of 4-O-methylglucuronic acid from birchwood xylan. The enzyme acts synergistically with endoxylanases and beta-xylosidase in the hydrolysis of xylan. The enzyme is N glycosylated and contains 14 putative N-glycosylation sites. The gene encoding this alpha-glucuronidase (aguA) was cloned from A. tubingensis. It consists of an open reading frame of 2,523 bp and contains no introns. The gene codes for a protein of 841 amino acids, containing a eukaryotic signal sequence of 20 amino acids. The mature protein has a predicted molecular mass of 91,790 Da and a calculated pI of 5.13. Multiple copies of the gene were introduced in A. tubingensis, and expression was studied in a highly overproducing transformant. The aguA gene was expressed on xylose, xylobiose, and xylan, similarly to genes encoding endoxylanases, suggesting a coordinate regulation of expression of xylanases and alpha-glucuronidase. Glucuronic acid did not induce the expression of aguA and also did not modulate the expression on xylose. Addition of glucose prevented expression of aguA on xylan but only reduced the expression on xylose.

  6. Potent quinoxaline-spaced phosphono alpha-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation.

    Science.gov (United States)

    Baudy, R B; Greenblatt, L P; Jirkovsky, I L; Conklin, M; Russo, R J; Bramlett, D R; Emrey, T A; Simmonds, J T; Kowal, D M; Stein, R P

    1993-02-01

    A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H] CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [3H]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic++ + acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 microM.

  7. Transcriptional regulation of the human acid alpha-glucosidase gene. Identification of a repressor element and its transcription factors Hes-1 and YY1.

    Science.gov (United States)

    Yan, B; Heus, J; Lu, N; Nichols, R C; Raben, N; Plotz, P H

    2001-01-19

    Acid alpha-glucosidase, the product of a housekeeping gene, is a lysosomal enzyme that degrades glycogen. A deficiency of this enzyme is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenesis type II. We have previously demonstrated that the human acid alpha-glucosidase gene expression is regulated by a silencer within intron 1, which is located in the 5'-untranslated region. In this study, we have used deletion analysis, electrophoretic mobility shift assay, and footprint analysis to further localize the silencer to a 25-base pair element. The repressive effect on the TK promoter was about 50% in both orientations in expression plasmid, and two transcriptional factors were identified with antibodies binding specifically to the element. Mutagenesis and functional analyses of the element demonstrated that the mammalian homologue 1 of Drosophila hairy and Enhancer of split (Hes-1) binding to an E box (CACGCG) and global transcription factor-YY1 binding to its core site function as a transcriptional repressor. Furthermore, the overexpression of Hes-1 significantly enhanced the repressive effect of the silencer element. The data should be helpful in understanding the expression and regulation of the human acid alpha-glucosidase gene as well as other lysosomal enzyme genes.

  8. Entrapment of alpha1-acid glycoprotein in high-performance affinity columns for drug-protein binding studies.

    Science.gov (United States)

    Bi, Cong; Jackson, Abby; Vargas-Badilla, John; Li, Rong; Rada, Giana; Anguizola, Jeanethe; Pfaunmiller, Erika; Hage, David S

    2016-05-15

    A slurry-based method was developed for the entrapment of alpha1-acid glycoprotein (AGP) for use in high-performance affinity chromatography to study drug interactions with this serum protein. Entrapment was achieved based on the physical containment of AGP in hydrazide-activated porous silica supports and by using mildly oxidized glycogen as a capping agent. The conditions needed for this process were examined and optimized. When this type of AGP column was used in binding studies, the association equilibrium constant (Ka) measured by frontal analysis at pH 7.4 and 37°C for carbamazepine with AGP was found to be 1.0 (±0.5)×10(5)M(-1), which agreed with a previously reported value of 1.0 (±0.1)×10(5)M(-1). Binding studies based on zonal elution were conducted for several other drugs with such columns, giving equilibrium constants that were consistent with literature values. An entrapped AGP column was also used in combination with a column containing entrapped HSA in a screening assay format to compare the binding of various drugs to AGP and HSA. These results also agreed with previous data that have been reported in literature for both of these proteins. The same entrapment method could be extended to other proteins and to the investigation of additional types of drug-protein interactions. Potential applications include the rapid quantitative analysis of biological interactions and the high-throughput screening of drug candidates for their binding to a given protein.

  9. R-alpha-methylhistamine-induced inhibition of gastric acid secretion in pylorus-ligated rats via central histamine H3 receptors.

    OpenAIRE

    Barocelli, E; Ballabeni, V.; Chiavarini, M.; Impicciatore, M

    1995-01-01

    1. The effect of central H3 histamine receptor activation on gastric acid and pepsin production has been investigated in pylorus-ligated rats. 2. Intracerebroventricular injections (i.c.v.) of the selective H3 agonist, R-alpha-methylhistamine (0.5-50 nmol per rat) caused a dose-dependent inhibition of gastric acid secretion while intravenous administration (5-500 nmol per rat) was completely ineffective. 3. I.c.v. microinjections of mepyramine, tiotidine and thioperamide (51 nmol per rat), se...

  10. Zinc-promoted simple synthesis of oligomer-free N(alpha)-Fmoc-amino acids using Fmoc-Cl as an acylating agent under neutral conditions.

    Science.gov (United States)

    Gopi, H N; Suresh Babu, V V

    2000-04-01

    A range of N(alpha)-Fmoc-protected amino acids, including those that contain t-butyl moiety, have been synthesized by employing Fmoc-Cl utilizing the activated, commercial zinc dust-promoted synthesis of carbamates under neutral conditions. A general procedure is described that circumvents the oligomerization side reaction normally noticed in Schotten-Baumann conditions. It is a simple, convenient and clean method. Thus, Fmoc-amino acids are obtained in high yield (85-92%) and purity as checked by thin-layer chromatography, high-performance liquid chromatography and other physical methods.

  11. R-alpha-methylhistamine-induced inhibition of gastric acid secretion in pylorus-ligated rats via central histamine H3 receptors.

    Science.gov (United States)

    Barocelli, E; Ballabeni, V; Chiavarini, M; Impicciatore, M

    1995-08-01

    1. The effect of central H3 histamine receptor activation on gastric acid and pepsin production has been investigated in pylorus-ligated rats. 2. Intracerebroventricular injections (i.c.v.) of the selective H3 agonist, R-alpha-methylhistamine (0.5-50 nmol per rat) caused a dose-dependent inhibition of gastric acid secretion while intravenous administration (5-500 nmol per rat) was completely ineffective. 3. I.c.v. microinjections of mepyramine, tiotidine and thioperamide (51 nmol per rat), selective antagonists at H1-, H2- and H3-sites respectively, failed to modify the acid secretory response to pylorus ligation. 4. The antisecretory effect of R-alpha-methylhistamine (5 nmol per rat, i.c.v.) was selectively prevented by the H3-blocker, thioperamide (51 nmol per rat, i.c.v.), mepyramine and tiotidine pretreatment being completely inactive. 5. Unlike acid secretion, pepsin production was not significantly affected by all the tested compounds. 6. These findings provide the first pharmacological evidence that the activation of central H3 histamine receptors exerts a negative control in the regulation of gastric acid secretion in conscious pylorus-ligated rats.

  12. Regulation of topoisomerase II alpha and beta in HIV-1 infected and uninfected neuroblastoma and astrocytoma cells: involvement of distinct nordihydroguaretic acid sensitive inflammatory pathways.

    Science.gov (United States)

    Mandraju, Raj Kumar; Kondapi, Anand K

    2007-05-01

    The activity of Topoisomerase II alpha and beta isoforms is tightly regulated during different phases of cell cycle. In the present study, the action of anti-inflammatory agents, nordihydroguaretic acid (NDGA) is analyzed in HIV-1 infected CXCR4(+), CCR5(+) and CD4(-) SK-N-SH neuroblastoma, CXCR4(+), CCR5(+) and CD4(-) 1321N1 astrocytoma and CXCR4(+), CCR5(+/-) and CD4(-) GO-G-CCM glioblastoma cell lines. In SK-N-SH and 1321N1 the expression of Topoisomerase II alpha is concomitant with that of LOX-5 and is highly sensitive to NDGA, while the Topoisomerase II beta is expressed along with TNFalpha and exhibits low sensitivity to NDGA, suggesting distinct pathways of regulation for the two isoforms. HIV-1 infection in these cells enhanced the expression of Topo II alpha and beta. Further, the regulation of Topo II beta and TNFalpha in infected and uninfected SK cells is distinctly different. HIV-1 gp120 derived peptides could block HIV-1 mediated inflammation and Topoisomerase II alpha and beta expression, suggesting the viral mediated response. A combination of NDGA, gp-120 derived peptides and AZT has completely blocked the viral replication, suggesting the enhancement of potency of AZT under the suppression of inflammatory response. In contrast, the expression of Topo II alpha and beta was stimulated by NDGA in GO-G-CCM cells showing distinct regulatory pathway in these cells that was resistant to HIV-1 infection. This suggests the requirement of inflammatory response for productive viral infection. In summary, an induction of co-receptor mediated inflammatory response can distinctly enhance regulated expression of the cellular Topo II alpha and beta and promote productive infection in neurons and astrocytes.

  13. Stoichiometry of expressed alpha(4)beta(2)delta gamma-aminobutyric acid type A receptors depends on the ratio of subunit cDNA transfected.

    Science.gov (United States)

    Wagoner, Kelly R; Czajkowski, Cynthia

    2010-05-07

    The gamma-aminobutyric acid type A receptor (GABA(A)R) is the target of many depressants, including benzodiazepines, anesthetics, and alcohol. Although the highly prevalent alphabetagamma GABA(A)R subtype mediates the majority of fast synaptic inhibition in the brain, receptors containing delta subunits also play a key role, mediating tonic inhibition and the actions of endogenous neurosteroids and alcohol. However, the fundamental properties of delta-containing GABA(A)Rs, such as subunit stoichiometry, are not well established. To determine subunit stoichiometry of expressed delta-containing GABA(A)Rs, we inserted the alpha-bungarotoxin binding site tag in the alpha(4), beta(2), and delta subunit N termini. An enhanced green fluorescent protein tag was also inserted into the beta(2) subunit to shift its molecular weight, allowing us to separate subunits using SDS-PAGE. Tagged alpha(4)beta(2)delta GABA(A)Rs were expressed in HEK293T cells using various ratios of subunit cDNA, and receptor subunit stoichiometry was determined by quantitating fluorescent alpha-bungarotoxin bound to each subunit on Western blots of surface immunopurified tagged GABA(A)Rs. The results demonstrate that the subunit stoichiometry of alpha(4)beta(2)delta GABA(A)Rs is regulated by the ratio of subunit cDNAs transfected. Increasing the ratio of delta subunit cDNA transfected increased delta subunit incorporation into surface receptors with a concomitant decrease in beta(2) subunit incorporation. Because receptor subunit stoichiometry can directly influence GABA(A)R pharmacological and functional properties, considering how the transfection protocols used affect subunit stoichiometry is essential when studying heterologously expressed alpha(4)beta(2)delta GABA(A)Rs. Successful bungarotoxin binding site tagging of GABA(A)R subunits is a novel tool with which to accurately quantitate subunit stoichiometry and will be useful for monitoring GABA(A)R trafficking in live cells.

  14. Alpha Hydroxy Acids

    Science.gov (United States)

    ... significant differences in UV sensitivity among the various skin sites. The studies did not identify exactly how AHAs bring about ... in UV-induced damage to DNA in the skin. Previous FDA studies have indicated that a cosmetic-type cream base ...

  15. Effect of pH, urea, peptide length, and neighboring amino acids on alanine alpha-proton random coil chemical shifts.

    Science.gov (United States)

    Carlisle, Elizabeth A; Holder, Jessica L; Maranda, Abby M; de Alwis, Adamberage R; Selkie, Ellen L; McKay, Sonya L

    2007-01-01

    Accurate random coil alpha-proton chemical shift values are essential for precise protein structure analysis using chemical shift index (CSI) calculations. The current study determines the chemical shift effects of pH, urea, peptide length and neighboring amino acids on the alpha-proton of Ala using model peptides of the general sequence GnXaaAYaaGn, where Xaa and Yaa are Leu, Val, Phe, Tyr, His, Trp or Pro, and n = 1-3. Changes in pH (2-6), urea (0-1M), and peptide length (n = 1-3) had no effect on Ala alpha-proton chemical shifts. Denaturing concentrations of urea (8M) caused significant downfield shifts (0.10 +/- 0.01 ppm) relative to an external DSS reference. Neighboring aliphatic residues (Leu, Val) had no effect, whereas aromatic amino acids (Phe, Tyr, His and Trp) and Pro caused significant shifts in the alanine alpha-proton, with the extent of the shifts dependent on the nature and position of the amino acid. Smaller aromatic residues (Phe, Tyr, His) caused larger shift effects when present in the C-terminal position (approximately 0.10 vs. 0.05 ppm N-terminal), and the larger aromatic tryptophan caused greater effects in the N-terminal position (0.15 ppm vs. 0.10 C-terminal). Proline affected both significant upfield (0.06 ppm, N-terminal) and downfield (0.25 ppm, C-terminal) chemical shifts. These new Ala correction factors detail the magnitude and range of variation in environmental chemical shift effects, in addition to providing insight into the molecular level interactions that govern protein folding.

  16. Food sources of alpha-linolenic acid (PFA 18:3), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

    Science.gov (United States)

    Food sources of alpha-linolenic acid (PFA 18:3), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

  17. Experimental and theoretical studies on the inclusion complexation of syringic acid with alpha-, beta-, gamma- and heptakis(2,6-di-O-methyl)-beta-cyclodextrin.

    Science.gov (United States)

    Song, Le Xin; Wang, Hai Ming; Xu, Peng; Yang, Yan; Zhang, Zi Qiang

    2008-04-01

    Intermolecular interactions of alpha-, beta-, gamma- and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (CD) with syringic acid (Syr) in aqueous solution are investigated by fluorescence spectroscopy. The fluorescence intensity of Syr gradually increases with the addition of the CDs. The formation constants (K) of the host-guest inclusion complexes are determined using a nonlinear analysis. The association abilities of Syr with the CDs decrease in the order gamma->beta->alpha- approximately DMbeta-CD. Both the intrinsic binding abilities of the CDs and the structural effect of Syr are taken into consideration when comparing the K values. Based on the results of NMR experimental and theoretical PM3 calculations both in vacuo and in water, it is found that Syr stays near the wider rim of alpha-CD cavity. Both the number of substituted groups (NSG) in a guest and the molar volume ratio of the guest to host cavity (MVR) play an important role in forming the CD supramolecular complexes of a homologous series of phenol derivatives, such as 2-methoxylphenol (2-Mop), eugenol (Eug) and Syr, i.e., an appropriate NSG or MVR in an inclusion system, such as in 2-Mop-alpha-CD, Eug-beta-CD and Syr-gamma-CD systems, can maximize the intermolecular interaction between host and guest.

  18. Alpha Thalassemia

    Science.gov (United States)

    Alpha Thalassemia Physicians often mistake alpha thalassemia trait for iron deficiency anemia and incorrectly prescribe iron supplements that have no effect 1 on the anemia. αα αα Normal alpha ...

  19. Improvement of the mechanical properties of an {alpha}-TCP cement by the addition of a polymeric drug containing salicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Ginebra, M.P.; Rilliard, A.; Fernandez, E.; Planell, J.A. [Universidad Politecnica de Cataluna, Barcelona (Spain). Dept. of Materials Science and Metallurgical Engineering; Elvira, C.; San Roman, J. [CSIC, Madrid (Spain). Inst. de Ciencia y Tecnologia de Polimeros

    2001-07-01

    The aim of this work is to study the possibility to improve the mechanical properties of a calcium phosphate cement by adding a polymeric acrylic system supporting a derivative of the aminosalicylic acid. It is shown that besides the analgesic and antiinflammatory properties, the salicylic group present a calcium complexation ability. This feature makes it reasonable to envisage a good bonding between the inorganic and the polymeric phase, which can act as a reinforcing component in the cement. The inorganic phase of the cement studied consisted in {alpha}- tricalcium phosphate ({alpha}-Ca{sub 3}(PO{sub 4}){sub 2}) and precipitated hydroxyapatite as a seed, and the liquid phase was an aqueous solution of Na{sub 2}HPO{sub 4}. The polymeric drug used (poly (4-HMA), where 4-HMA is a methacrylamide derived from 4-aminosalicylic acid) was added in a 5 wt% to the liquid phase. The hydrolysis of the {alpha}-TCP into hydroxyapatite was not prevented, but the polymer produced a delay in the reaction. As a consequence the cement hardening was slightly slower, although the final compressive strength was 25% higher. The bending strength increased noticeably, from 5 MPa to 9 MPa with the addition of the polymeric drug. The strengthening of the structure could be related by SEM observations with the formation of a polymeric network between the entangled crystals of hydroxyapatite. (orig.)

  20. Diversity of function in the isocitrate lyase enzyme superfamily: the Dianthus caryophyllus petal death protein cleaves alpha-keto and alpha-hydroxycarboxylic acids.

    Science.gov (United States)

    Lu, Zhibing; Feng, Xiaohua; Song, Ling; Han, Ying; Kim, Alexander; Herzberg, Osnat; Woodson, William R; Martin, Brian M; Mariano, Patrick S; Dunaway-Mariano, Debra

    2005-12-20

    The work described in this paper was carried out to define the chemical function a new member of the isocitrate lyase enzyme family derived from the flowering plant Dianthus caryophyllus. This protein (Swiss-Prot entry Q05957) is synthesized in the senescent flower petals and is named the "petal death protein" or "PDP". On the basis of an analysis of the structural contexts of sequence markers common to the C-C bond lyases of the isocitrate lyase/phosphoenolpyruvate mutase superfamily, a substrate screen that employed a (2R)-malate core structure was designed. Accordingly, stereochemically defined C(2)- and C(3)-substituted malates were synthesized and tested as substrates for PDP-catalyzed cleavage of the C(2)-C(3) bond. The screen identified (2R)-ethyl, (3S)-methylmalate, and oxaloacetate [likely to bind as the hydrate, C(2)(OH)(2) gem-diol] as the most active substrates (for each, k(cat)/K(m) = 2 x 10(4) M(-)(1) s(-)(1)). In contrast to the stringent substrate specificities previously observed for the Escherichia coli isocitrate and 2-methylisocitrate lyases, the PDP tolerated hydrogen, methyl, and to a much lesser extent acetate substituents at the C(3) position (S configuration only) and hydoxyl, methyl, ethyl, propyl, and to a much lesser extent isobutyl substituents at C(2) (R configuration only). It is hypothesized that PDP functions in oxalate production in Ca(2+) sequestering and/or in carbon scavenging from alpha-hydroxycarboxylate catabolites during the biochemical transition accompanying petal senescence.

  1. Estimation of free energy barriers in the cytoplasmic and mitochondrial aspartate aminotransferase reactions probed by hydrogen-exchange kinetics of C alpha-labeled amino acids with solvent

    Energy Technology Data Exchange (ETDEWEB)

    Julin, D.A.; Wiesinger, H.; Toney, M.D.; Kirsch, J.F. (Univ. of California, Berkeley (USA))

    1989-05-02

    The existence of the postulated quinonoid intermediate in the cytoplasmic aspartate amino-transferase catalyzed transamination of aspartate to oxaloacetate was probed by determining the extent of transfer of tritium from the C alpha position of tritiated L-aspartate to pyridoxamine 5'-phosphate in single turnover experiments in which washout from the back-reaction was obviated by product trapping. The maximum amount of transferred tritium observed was 0.7%, consistent either with a mechanism in which a fraction of the net transamination reaction proceeds through a quinonoid intermediate or with a mechanism in which this intermediate is formed off the main reaction pathway. It is shown that transfer of labeled hydrogen from the amino acid to cofactor cannot be used to differentiate a stepwise from a concerted transamination mechanism. The amount of tritium transferred is a function of the rate constant for torsional equilibration about the epsilon-amino group of Lys-258, the presumptive abstractor of the C alpha proton; the relative rate constants for hydrogen exchange with solvent versus cofactor protonation; and the tritium isotope effect on this ratio. The free energy barriers facing the covalent intermediate between aldimine and keto acid product (i.e., ketimine and possibly quinonoid) were evaluated relatively by comparing the rates of C alpha-hydrogen exchange in starting amino acid with the rates of keto acid formation. The value of theta (= kexge/kprod) was found to be 2.6 for the reaction of cytoplasmic isozyme with aspartate and ca. 0.5 for that of the mitochondrial form with glutamate.

  2. Interaction between retinoid acid receptor-related orphan receptor alpha (RORA and neuropeptide S receptor 1 (NPSR1 in asthma.

    Directory of Open Access Journals (Sweden)

    Nathalie Acevedo

    Full Text Available Retinoid acid receptor-related Orphan Receptor Alpha (RORA was recently identified as a susceptibility gene for asthma in a genome-wide association study. To investigate the impact of RORA on asthma susceptibility, we performed a genetic association study between RORA single nucleotide polymorphisms (SNPs in the vicinity of the asthma-associated SNP (rs11071559 and asthma-related traits. Because the regulatory region of a previously implicated asthma susceptibility gene, Neuropeptide S receptor 1 (NPSR1, has predicted elements for RORA binding, we hypothesized that RORA may interact biologically and genetically with NPSR1. 37 RORA SNPs and eight NPSR1 SNPs were genotyped in the Swedish birth cohort BAMSE (2033 children and the European cross-sectional PARSIFAL study (1120 children. Seven RORA SNPs confined into a 49 kb region were significantly associated with physician-diagnosed childhood asthma. The most significant association with rs7164773 (T/C was driven by the CC genotype in asthma cases (OR = 2.0, 95%CI 1.36-2.93, p = 0.0003 in BAMSE; and 1.61, 1.18-2.19, p = 0.002 in the combined BAMSE-PARSIFAL datasets, respectively, and strikingly, the risk effect was dependent on the Gln344Arg mutation in NPSR1. In cell models, stimulation of NPSR1 activated a pathway including RORA and other circadian clock genes. Over-expression of RORA decreased NPSR1 promoter activity further suggesting a regulatory loop between these genes. In addition, Rora mRNA expression was lower in the lung tissue of Npsr1 deficient mice compared to wildtype littermates during the early hours of the light period. We conclude that RORA SNPs are associated with childhood asthma and show epistasis with NPSR1, and the interaction between RORA and NPSR1 may be of biological relevance. Combinations of common susceptibility alleles and less common functional polymorphisms may modify the joint risk effects on asthma susceptibility.

  3. The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Yarrow Joshua F

    2007-07-01

    Full Text Available Abstract Background This study examined the efficacy of short-term alpha-ketoisocaproic acid (KIC monotherapy supplementation immediately prior to moderate- and high-intensity single bout exercise performance. Methods Thirteen resistance trained men (22.8 ± 2.5 years; 81.6 ± 12.6 kg participated in a prospective, randomized, double blind, placebo controlled crossover experiment. Each subject completed one familiarization and four experimental trials with either 1.5 g or 9.0 g of either KIC or isocaloric placebo control (CONT, following an overnight fast. During the experimental trials, subjects consumed the supplement regimen and then completed leg and chest press repetitions to failure and 30 s of repeated maximal vertical jumping (VJ on a force plate. Results In this treatment regimen, no significant differences (p > 0.05 were observed between dosages or conditions for leg press (low CONT = 19.8 ± 0.4 SEM, low KIC = 21.0 ± 0.5, high CONT = 20.1 ± 0.3, high KIC = 22.4 ± 0.6 or chest press (low CONT = 18.1 ± 0.2, low KIC = 18.5 ± 0.3, high CONT = 17.8 ± 0.3, high KIC = 18.0 ± 0.3 repetitions to failure. Additionally, no significant differences were observed for peak or mean VJ performance (low CONT = 34.6 ± 2.2 cm and 28.6 ± 1.8 cm; low KIC = 35.6 ± 2.0 cm and 29.4 ± 1.6 cm; high CONT = 35.7 ± 2.1 cm and 29.4 ± 1.7 cm; high KIC = 34.8 ± 2.3 cm and 28.3 ± 1.7 cm, respectively. Conclusion Based on our results, we conclude that acute KIC ingestion by itself with no other ergogenic supplement, immediately prior to exercise, did not alter moderate- nor high-intensity single-bout exercise performance in young resistance-trained males. This study addressed single-dose single-bout performance events; the efficacy of KIC monotherapy supplementation on repeated high-intensity exercise bouts and long-term exercise training remains unknown.

  4. P-Nitrobenzoic acid alpha2u nephropathy in 13-week studies is not associated with renal carcinogenesis in 2-year feed studies.

    Science.gov (United States)

    Williams, K D; Dunnick, J; Horton, J; Greenwell, A; Eldridge, S R; Elwell, M; Sills, R C

    2001-01-01

    The objective of this study was to characterize the renal toxicity and carcinogenicity of p-nitrobenzoic acid in F344 rats. Dose levels in 13-week and 2-year studies ranged from 630-10,000 ppm and 1,250-5,000 ppm, respectively. At 13 weeks, renal lesions included minimal to mild hyaline droplet accumulation in male rats and karyomegaly in male and female rats. At 2 years, renal lesions included proximal tubule epithelial cell hyperplasia in male rats and oncocytic hyperplasia in high-dose male and female rats, and a decreased severity of nephropathy in males and females. The hvaline droplets in renal tubular epithelial cells of male rats at 13 weeks were morphologically similar to those described in alpha2u-globulin nephropathy. Using immunohistochemical methods, alpha2u-globulin accumulation was associated with the hyaline droplets. In addition, at 13 weeks, cell proliferation as detected by PCNA immunohistochemistry was significantly increased in males exposed to 5,000 and 10,000 ppm when compared to controls. Cytotoxicity associated with alpha2U-globulin nephropathy such as single-cell necrosis of the P2 segment epithelium or accumulation of granular casts in the outer medulla did not occur in the 13-week study. In addition, chronic treatment related nephrotoxic lesions attributed to accumulation of alpha2u-globulin such as linear foci of mineralization within the renal papilla, hyperplasia of the renal pelvis urothelium and kidney tumors were not observed. Although there was histologic evidence of alpha2u-globulin accumulation in male rats at 13 weeks, the minimal severity of nephropathy suggests that the degree of cytotoxicity was below the threshold, which would contribute to the development of renal tumors at 2 years.

  5. TNF-alpha and 9-cis-retinoic acid synergistically induce ICAM-1 expression: evidence for interaction of retinoid receptors with NF-kappa B.

    Science.gov (United States)

    Chadwick, C C; Shaw, L J; Winneker, R C

    1998-03-15

    TNF-alpha and 9-cis-retinoic acid (9-cis-R) synergistically enhance ICAM-1 protein expression in immortalized human aortic endothelial cells (HAECTs). At a TNF-alpha concentration of 0.1 ng/ml, 1 microM 9-cis-R enhanced ICAM-1 protein expression 4-fold. Treatment with 1 microM 9-cis-R alone caused no induction of ICAM-1 expression. Functional analysis of human ICAM-1 promoter-luciferase constructs revealed that the synergism was attributable to transcriptional regulation. Expression of a luciferase reporter vector containing a 311-bp fragment of the ICAM-1 promoter (-252 to + 59 bp relative to the transcriptional start site) was increased 2.9- and 4.9-fold by treatment with 9-cis-R and TNF-alpha, respectively, while cotreatment with 9-cis-R and TNF-alpha induced expression to 19.9-fold. Mutation studies revealed that RARE and NF-kappa B sites located respectively at -226 and -188 bp relative to the transcription start site are essential for the synergistic control of promoter activity. Mutation of either the RARE or the NF-kappa B site eliminated the synergistic enhancement of promoter activity. Moreover, mutation of the RARE abrogated promoter activity induced by treatment with TNF-alpha alone and mutation of the NF-kappa B site eliminated promoter activity induced by treatment with 9-cis-R alone. We conclude that retinoid receptors and NF-kappa B act in concert at the promoter level to facilitate ICAM-1 expression in endothelial cells.

  6. Brucine salts of L-alpha-hydroxy acids: brucinium hydrogen (S)-malate pentahydrate and anhydrous brucinium hydrogen (2R,3R)-tartrate at 130 K.

    Science.gov (United States)

    Smith, Graham; Wermuth, Urs D; White, Jonathan M

    2006-06-01

    The structures of two brucinium (2,3-dimethoxy-10-oxostrychnidinium) salts of the alpha-hydroxy acids L-malic acid and L-tartaric acid, namely brucinium hydrogen (S)-malate pentahydrate, C23H27N2O4+.C4H5O5-.5H2O, (I), and anhydrous brucinium hydrogen (2R,3R)-tartrate, C23H27N2O4+.C4H5O6-,(II), have been determined at 130 K. Compound (I) has two brucinium cations, two hydrogen malate anions and ten water molecules of solvation in the asymmetric unit, and forms an extensively hydrogen-bonded three-dimensional framework structure. In compound (II), the brucinium cations form the common undulating brucine sheet substructures, which accommodate parallel chains of head-to-tail hydrogen-bonded tartrate anion species in the interstitial cavities.

  7. Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure

    Directory of Open Access Journals (Sweden)

    Rousseau-Ralliard Delphine

    2009-03-01

    Full Text Available Abstract Background Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA in rats requires a long feeding period (6 months, although a docosahexaenoic (DHA acid-supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n-3 polyunsaturated fatty acid (PUFA composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL, mitochondrial (MI, nuclear (NU and sarcoplasmic reticulum (SR membrane fractions. Methods Male Wistar rats were randomly assigned to 3 dietary groups (n = 10/diet/period, either n-3 PUFA-free diet (CTL, or ALA or DHA-rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC after lipid extraction. Results As expected the n-3 PUFA-rich diets incorporated n-3 PUFA instead of n-6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n-3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n-3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA. N-3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing. Conclusion With the ALA diet the n-3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response.

  8. Construction and expression of nucleic acid vaccine pVAXl-h-alpha S1-14o coding human alpha-synuclein

    Institute of Scientific and Technical Information of China (English)

    Jiacai Wang; Yingsong Ouyang; Shaojun Wang; Guoguang Peng; Qin Luo; Side Jiang; Faxiang Wang

    2008-01-01

    BACKGROUND: The deposition of α-synuclein (α-syn) aggregates is a neuropathological feature of Parkinson's disease. It remains impossible to involve α-syn aggregation in the treatment of Parkinson's disease. A nucleic acid vaccine will provide a new pathway to immunotherapy for Parkinson's disease.OBJECTIVE: To construct a recombinant eukaryotic expression vector pVAX1 coding human α-syn and to observe its expression level in COS-7 cells.DESIGN AND SETTING: The present bioengineering and molecular biology experiment was performed at Department of Neurology, First Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Neurology.MATERIALS: The eukaryotic expression plasmid pVAX1, human embryonic brain tissue, healthy human blood cells, and COS-7 cells were purchased from Promega Company, USA.METHODS: The full-length CDS sequence of the human α-syn gene was amplified by RT-PCR, which contained restriction sites for the enzymes Kpn I, Xba I and Kozak consensus sequence. Then the PCR products and eukaryotic expression vector pVAX1 were digested with Kpn I and Xba I simultaneously, and were extracted and ligated by T4 ligase. The recombinant constructs pVAXI-hα-S1-14o were transformed into competent E. coli TOP 10 cells and the positive clones were screened and selected using PCR analysis,restriction digestion analysis, and DNA sequencing. The constructs were then tested for protein expression in COS-7 cells by RT-PCR and Western blotting.MAIN OUTCOME MEASURES: Identification of an eukaryotic expression vector containing the human α-syn gene, pVAX1-hα-S1-140, and detection of the expression in mammalian cell COS-7.RESULTS: The pVAXi vector was successfully cloned with human a -syn in the correct orientation and in-frame. The DNA vaccine constructs pVAX1-hα-S1-140 with the human α-syn gene were shown to be expressed in COS-7 cells. Human α-syn was successfully expressed in the mammalian cell line and was detected by RT-PCR and western

  9. Studies in lipid histochemistry. XIII. The OPA (osmiumtetroxide-periodic acid-alpha-naphthylamine) method for the detection of apolar lipids.

    Science.gov (United States)

    Elleder, M

    1975-09-29

    A new procedure for the detection of apolar lipids is described. It is a modification of the OTAN method (Adams, 1959) using periodic acid which oxidatively removes lower osmium derivatives from polar sites only, leaving those in apolar lipids intact and demonstrable with alpha-naphthylamine. Control steps for the exclusion of the possible interference of some less polar complex lipids and of lipopigments are described. The described technic is superior to the conventionally used sudan dyes due partly to the fact that only aqueous solutions are employed thus excluding any extraction of lipids, partly to the more distinct coloration.

  10. Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase

    DEFF Research Database (Denmark)

    Hansen, Torben; Andersen, C B; Echwald, Søren Morgenthaler

    1997-01-01

    in a phenotype study. Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation...

  11. Altered TNF-Alpha, Glucose, Insulin and Amino Acids in Islets Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.

    2001-01-01

    The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-1 17,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (parginine in islets cultured in HARVs. While nitrogenous compound analysis indicated a ubiquitous reliance upon glutamine in all experimental groups, arginine was converted to ornithine at a two-fold greater rate in the islets cultured in the HARV microgravity model system (p<0.05). These studies demonstrate alterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  12. Effects of niflumic acid on alpha1-adrenoceptor-induced vasoconstriction in mesenteric artery in vitro and in vivo in two-kidney one-clip hypertensive rats.

    Science.gov (United States)

    He, Y; Tabrizchi, R

    1997-06-11

    The influence of niflumic acid (3 and 10 microM), a Cl- channel antagonist, on cirazoline-induced vasoconstriction in isolated perfused mesenteric artery (5 ml/min) from two-kidney one-clip (2K1C) hypertensive and sham normotensive rats was examined. In addition, the effect of a single i.v. bolus injection of niflumic acid (3 mg/kg) on cirazoline-mediated reduction in vascular conductance in superior mesenteric artery was determined in pentobarbital-anaesthetized hypertensive and normotensive rats. Bolus injections of cirazoline induced a dose-dependent transient increase in the perfusion pressure in vitro. In the presence of niflumic acid, cirazoline-mediated vasoconstriction was significantly inhibited. Cirazoline-induced vasoconstriction in isolated mesenteric beds was also significantly inhibited following perfusion with Cl(-)-free buffer. Pre-perfusion of mesenteric blood vessels with Cl(-)-free buffer resulted in a significantly greater inhibition of cirazoline-mediated vasoconstriction in sham normotensive rats than in hypertensive rats. We found that in Cl(-)-free buffer, cirazoline-mediated vasoconstriction could be further inhibited by niflumic acid. Intravenous infusion of cumulative doses of cirazoline in vivo caused a dose-dependent decrease in superior mesenteric vascular conductance. Pretreatment with niflumic acid significantly impaired cirazoline-mediated decreases in vascular conductance. Our results indicate that chloride ions play an important role in alpha1-adrenoceptor-mediated vasoconstriction in mesenteric blood vessels. In addition, the contribution of chloride ions in alpha1-adrenoceptor-mediated vasoconstriction in blood vessels from hypertensive rats appears to be reduced.

  13. Ultraviolet irradiation of DNA complexed with. alpha. /. beta. -type small, acid-soluble proteins from spores of Bacillus or Clostridium species makes spore photoproduct but not thymine dimers

    Energy Technology Data Exchange (ETDEWEB)

    Nicholson, W.L.; Setlow, B.; Setlow, P. (Univ. of Connecticut Health Center, Farmington (United States))

    1991-10-01

    UV irradiation of complexes of DNA and an {alpha}/{beta}-type small, acid-soluble protein (SASP) from Bacillus subtilis spores gave decreasing amounts of pyrimidine dimers and increasing amounts of spore photoproduct as the SASP/DNA ratio was increased. The yields of pyrimidine dimers and spore photoproduct were < 0.2% and 8% of total thymine, respectively, when DNA saturated with SASP was irradiated at 254 nm with 30 kJ/m{sup 2}; in the absence of SASP the yields were reversed - 4.5% and 0.3%, respectively. Complexes of DNA with {alpha}/{beta}-type SASP from Bacillus cereus, Bacillus megaterium, or Clostridium bifermentans spores also gave spore photoproduct upon UV irradiation. However, incubation of these SASPs with DNA under conditions preventing complex formation or use of mutant SASPs that do not form complexes did not affect the photoproducts formed in vitro. These results suggest that the UV photochemistry of bacterial spore DNA in vivo is due to the binding of {alpha}/{beta}-type SASP, a binding that is known to cause a change in DNA conformation in vitro from the B form to the A form. The yields of spore photoproduct in vitro were significantly lower than in vivo, perhaps because of the presence of substances other than SASP in spores. It is suggested that as these factors diffuse out in the first minutes of spore germination, spore photoproduct yields become similar to those observed for irradiation of SASP/DNA complexes in vitro.

  14. Effects of trefoil peptide 3 on expression of TNF-alpha, TLR4, and NF-kappaB in trinitrobenzene sulphonic acid induced colitis mice.

    Science.gov (United States)

    Teng, Xu; Xu, Ling-Fen; Zhou, Ping; Sun, Hong-Wei; Sun, Mei

    2009-04-01

    The trefoil factor (TFF) peptides are major secretory products of mucus cells of the gastrointestinal tract. There were evidences that administration of recombinant human TFF3 is effective in treatment of models of colitis, but the mechanism of the effects of rTFF3 is not fully understood. The main aims of this study is to evaluate effects of intraperitoneal injection recombinant human TFF3 on the expression of tumour necrosis factor alpha (TNF-alpha), toll-like receptor 4(TLR4), and nuclear factor kappaB (NF-kappaB) in trinitrobenzene sulphonic acid (TNBS) induced colitis mice. Distal colitis was induced in BALB/C mice by intracolonic administration of TNBS in ethanol. Treated with administration rhTFF3 for treatment group(5 mg/ml; approximately 0.5 mg/mouse), and normal saline for control for 5 consecutive days. Colonic damage score, tissue myeloperoxidase (MPO) activity, TLR4, NF-kappaB mRNA expression, and tissue TNF-alpha, TLR4, NF-kappaB production were determined, respectively. Once daily application of hTFF3 for 5 days after TNBS/ethanol had been injected, both microscopic and macroscopic injury and inflammatory index had been reduced compared with controls. In addition, decreased tissue TNF-alpha, TLR4, NF-kappaB production, and TLR4, NF-kappaB mRNA expression had been found. This study has shown that hTFF3 may have therapeutic potential in the treatment of inflammatory bowel disease, and one of the mechanisms may related to inhibit the TLR4/NF-kappaB signaling pathways.

  15. Degradation of alpha-pinene oxide and [2H7]-2,5,6-trimethyl-hept-(2E)-enoic acid by Pseudomonas fluorescens NCIMB 11761.

    Science.gov (United States)

    Zorn, H; Neuser, F; Berger, R G

    2004-02-01

    When submerged cultured Pseudomonas fluorescens NCIMB 11761 was fed-batch supplemented with alpha-pinene oxide, a rapid formation of 2,6-dimethyl-5-methylene-hept-(2Z)-enal (I) (isonovalal) was observed. Biotransformation and isomerisation of (I) to the (2E)-isomer (II) (novalal) were enhanced by Lewatit OC 1064, a macroporous polystyrene adsorbent. Accelerated isomerisation in the presence of an amino donor (glycine) at pH 7.3 pointed to a merely chemical mechanism. A maximum yield of 48 g of aldehydesl(-1) was achieved, but quantitative analysis of the volatile fraction showed that the molar conversion of the pinene oxide substrate reached no more than 67%. To fill this gap of the mass balance, the acidic fraction was isolated. It contained several compounds which suggested a beta-oxidation-like catabolism starting from 2,6-dimethyl-5-methylene-hept-(2E)-enoic acid (III) (novalic acid). Using [2H7]-2,5,6-dimethyl-hept-(2E)-enoic acid as a conversion substrate and gas chromatography coupled to atomic emission detection and mass spectrometry a degradation pathway via labelled 3,4-dimethylpentenoic and methylpropanoic acids was evidenced. This pathway may play a predominant role in isoprenoid degradation by soil bacteria.

  16. Amino acid sequences mediating vascular cell adhesion molecule 1 binding to integrin alpha 4: homologous DSP sequence found for JC polyoma VP1 coat protein

    Directory of Open Access Journals (Sweden)

    Michael Andrew Meyer

    2013-07-01

    Full Text Available The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4 to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3. For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer.

  17. Amino Acid Sequences Mediating Vascular Cell Adhesion Molecule 1 Binding to Integrin Alpha 4: Homologous DSP Sequence Found for JC Polyoma VP1 Coat Protein.

    Science.gov (United States)

    Meyer, Michael Andrew

    2013-01-01

    The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4) to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3). For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer.

  18. Further evidence of a relationship between the retinoic acid receptor alpha locus and nonsyndromic cleft lip with or without cleft palate (CL [+-] P)

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, D.; Field, L. (Univ. of Calgary (Canada)); Ray, A. (Univ. of Toronto (Canada)); Marazita, M. (Medical College of Virginia, Richmond, VA (United States))

    1993-11-01

    Chenevix-Trench et al. (1992) reported a significant difference between nonsyndromic cleft lip with or without cleft palate (CL [+-] P) cases and unrelated controls in the frequency of alleles at the retinoic acid receptor alpha (RARA) PstI RFLP located at 17q21.1. They also observed borderline significant (P = .055) differences between allele frequencies in subjects with cleft lip and palate (CL + P) compared with those with cleft lip only (CL). Retinoic acid (RA) is a known teratogen capable of producing cleft palate in rodents (Abbott and Birnbaum 1990). Chenevix-Tench et al. (1992) hypothesized that variation in susceptibility to the effects of RA in humans may result from alterations at the RARA locus. We have investigated association and linkage between CL [+-] P and a microsatellite marker (D17S579) located at 17q21 (Hall et al. 1992), selected for its proximity to RARA, in 14 extended multiplex families from rural West Bengal, India.

  19. alpha2-gamma-Aminobutyric acid (GABA)A receptors are the molecular substrates mediating precipitation of narcosis but not of sedation by the combined use of diazepam and alcohol in vivo.

    Science.gov (United States)

    Täuber, Marcus; Calame-Droz, Elisabeth; Prut, Laetitia; Rudolph, Uwe; Crestani, Florence

    2003-11-01

    Classical benzodiazepines such as diazepam are widely used tranquillisers and hypnotics in various neuropsychiatric diseases including alcohol-related disorders. One of the major drawbacks of benzodiazepine therapy, however, is an exacerbation of the sedative and hypnotic effects associated with alcohol intake, even at low doses. Even though the gamma-aminobutyric acid (GABA)A receptor complex is a common target for the actions of both classes of drugs, the molecular mechanisms underlying the enhanced pharmacological properties of the combined use of benzodiazepines and alcohol remain to be identified. The present experiments aimed at clarifying which of the GABAA receptor subtypes mediate the augmented hypnotic-like and sedative effects of combined diazepam and alcohol using the righting reflex and motor activity assays, respectively, in histidine-to-arginine point mutated mice that possess diazepam-insensitive alpha1-, alpha2-, alpha3- or alpha5-GABAA receptors. The combination of diazepam (2 or 3 mg/kg) and ethanol (3 g/kg) induced loss of righting reflex with a significantly dose-dependent increase of the latency to its full recovery in wild-type, alpha1(H101R), alpha3(H126R) and alpha5(H105R) but not in alpha2(H101R) mice. A combined treatment with diazepam (1 mg/kg) and ethanol (2.5 g/kg) precipitated motor inhibition similarly in wild-type and alpha2(H101R) mice. Responsiveness of the alpha2(H101R) mice to ethanol alone was similar to that of wild-type mice. These results demonstrate that induction of loss of righting reflex by combined diazepam and alcohol is closely dependent on the activation of the alpha2-GABAA receptors by the benzodiazepine whereas precipitation of sedation involves GABAA receptors other than the alpha2-GABAA receptors.

  20. Development of calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in cultured neocortical neurons visualized by cobalt staining

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S

    1998-01-01

    The developmental expression of calcium (Ca2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in cultured neocortical neurons was evaluated by using cobalt uptake, a histochemical method that identifies cells expressing Ca2+-permeable, non-N-methyl......The developmental expression of calcium (Ca2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in cultured neocortical neurons was evaluated by using cobalt uptake, a histochemical method that identifies cells expressing Ca2+-permeable, non......-N-methyl-D-aspartate (non-NMDA) receptors. At a concentration of 500 microM, AMPA was found to stimulate cobalt uptake only late in development, resulting in staining of 2.7%+/-0.3% of the neurons maintained in culture for 12 days in vitro (DIV). When AMPA receptor desensitization was blocked with 50 microM cyclothiazide......, the developmental profile of cobalt uptake mediated by 25 microM AMPA changed dramatically. The cobalt staining now appeared in young cultures (5 DIV), and the percentage of stained cells increased from 3.4%+/-0.2% at 5 DIV to 21.7%+/-1.6% at 12 DIV. The effect of 200 microM kainate was similar to that seen with 25...

  1. CACA-TOCSY with alternate {sup 13}C-{sup 12}C labeling: a {sup 13}C{sup {alpha}} direct detection experiment for mainchain resonance assignment, dihedral angle information, and amino acid type identification

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Koh [National Institute of Advanced Industrial Science and Technology (AIST), Biomedicinal Information Research Center (BIRC) (Japan); Frueh, Dominique P.; Sun, Zhen-Yu J.; Hiller, Sebastian; Wagner, Gerhard, E-mail: gerhard_wagner@hms.harvard.ed [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States)

    2010-05-15

    We present a {sup 13}C direct detection CACA-TOCSY experiment for samples with alternate {sup 13}C-{sup 12}C labeling. It provides inter-residue correlations between {sup 13}C{sup {alpha}} resonances of residue i and adjacent C{sup {alpha}s} at positions i - 1 and i + 1. Furthermore, longer mixing times yield correlations to C{sup {alpha}} nuclei separated by more than one residue. The experiment also provides C{sup {alpha}}-to-side chain correlations, some amino acid type identifications and estimates for {psi} dihedral angles. The power of the experiment derives from the alternate {sup 13}C-{sup 12}C labeling with [1,3-{sup 13}C] glycerol or [2-{sup 13}C] glycerol, which allows utilizing the small scalar {sup 3}J{sub CC} couplings that are masked by strong {sup 1}J{sub CC} couplings in uniformly {sup 13}C labeled samples.

  2. 硫辛酸注射液治疗糖病足及对患者血清MMP-9、Hcy的影响分析%Effects of Lipoic Acid Injection in the Treatment of Diabetic Foot and on Serum MMP-9、Hcy in Patients

    Institute of Scientific and Technical Information of China (English)

    任艳莉; 李可心

    2015-01-01

    Objective To explore the clinical efficacy of the treatment of diabetic foot with the treatment of MMP-9 (matrix metaloproteinase), and the effect of Hcy (homocysteine).Methods Select 66 cases of diabetic foot patients,digital table method is divided into the control group and the observation group,33 cases in each group,the control group were treated with cilostazol combined with conventional treatment,the observation group was treated with the combination of the conventional treatment of the combination of the sulfur acid injection,observe and compare the treatment effect of two groups of patients.Results The total effective rate of the observation group was higher than that of the control group(P < 0.05),the improvement of MMP-9 and Hcy in serum was better than that in control group(P < 0.05),the difference of the data is statisticaly significant. Conclusion Diabetic foot using the treatment of sulfur acid injection,patients with good results.%目的:探究糖尿病足采用硫辛酸注射液治疗的临床疗效及对患者血清MMP-9(基质金属蛋白酶)、Hcy(同型半胱氨酸)的影响。方法选取66例糖尿病足患者,以数字表法分为对照组和观察组各组均33例,对照组患者采用西洛他唑联合常规治疗,观察组患者采用硫辛酸注射液联合常规治疗,观察比较两组患者治疗效果。结果观察组患者治疗总有效率较对照组高(P <0.05),患者血清MMP-9、Hcy等指标改善程度优于对照组(P <0.05),各项数据比较差异均存在统计学意义。结论糖尿病足采用硫辛酸注射液治疗,患者治疗效果良好。

  3. A high-fat, high-oleic diet, but not a high-fat, saturated diet, reduces hepatic alpha-linolenic acid and eicosapentaenoic acid content in mice

    Science.gov (United States)

    Considerable research centers upon the role of linoleic acid (LNA; 18:2n6) as a competitive inhibitor of a-linolenic (ALA; 18:3n3) metabolism; however, little data exist as to the impact of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) on ALA metabolism. We tested the hypothesi...

  4. α硫辛酸抑制miR-29b表达抗氧化应激促进小鼠糖尿病足愈合的实验研究%EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE

    Institute of Scientific and Technical Information of China (English)

    吴军; 汤慧芹; 刘群; 干定云; 周曼

    2016-01-01

    目的 探讨α硫辛酸对糖尿病足小鼠创面组织氧化应激和创面愈合的影响.方法 取60只雄性C57BL/6J小鼠,体质量200~300 g,随机分为糖尿病足组(对照组)、α硫辛酸组、miR-29b mimic组及miR-29b mimic阴性对照组(NC组),每组15只.各组采用多次连续腹腔注射链脲佐菌素缓冲液制备2型糖尿病模型,4周后确定模型制备成功后于小鼠后背作大小为5 mm×2 mm的全层创面.之后各组均给予高脂高糖饮食;创面制备当天(第0天),α硫辛酸组开始尾静脉注射α硫辛酸(100 mg/kg),连续14 d;miR-29b mimic组及NC组在注射α硫辛酸基础上,于第0天分别注射慢病毒包装的miR-29b mimic及其阴性对照,病毒注射量为2×107 TU.术后观察各组创面愈合情况,于第7、14天测量并计算相对创面面积;第14天,取各组创面组织采用黄嘌呤氧化酶法和二硫代硝基苯甲酸(5,5-dithiobis-2-nitrobenzoic acid,DTNB)染色法分别测定组织中超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽(glutathione,GSH)含量;第0、7、14天,对照组以及α硫辛酸组取创面组织行实时荧光定量PCR检测miR-29b相对表达量.结果 各组小鼠均存活至实验完成.α硫辛酸组创面愈合速度快于对照组,其中第7、14天相对创面面积和miR-29b相对表达量显著低于对照组,而SOD和GSH含量显著高于对照组(P<0.05).miR-29b mimic组第7、14天相对创面面积较NC组显著增加,而创面组织中SOD和GSH含量显著低于NC组,比较差异均有统计学意义(P<0.05).结论 α硫辛酸通过抑制miR-29b表达进而抑制氧化应激,促进小鼠糖尿病足创面愈合.

  5. Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid.

    Science.gov (United States)

    García-García, Alejandro G; Polo-Hernández, Erica; Tabernero, Arantxa; Medina, José M

    2015-10-22

    We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development.

  6. Poly-alpha-glutamic acid synthesis using a novel catalytic activity of RimK from Escherichia coli K-12.

    Science.gov (United States)

    Kino, Kuniki; Arai, Toshinobu; Arimura, Yasuhiro

    2011-03-01

    Poly-L-α-amino acids have various applications because of their biodegradable properties and biocompatibility. Microorganisms contain several enzymes that catalyze the polymerization of L-amino acids in an ATP-dependent manner, but the products from these reactions contain amide linkages at the side residues of amino acids: e.g., poly-γ-glutamic acid, poly-ε-lysine, and cyanophycin. In this study, we found a novel catalytic activity of RimK, a ribosomal protein S6-modifying enzyme derived from Escherichia coli K-12. This enzyme catalyzed poly-α-glutamic acid synthesis from unprotected L-glutamic acid (Glu) by hydrolyzing ATP to ADP and phosphate. RimK synthesized poly-α-glutamic acid of various lengths; matrix-assisted laser desorption ionization-time of flight-mass spectrometry showed that a 46-mer of Glu (maximum length) was synthesized at pH 9. Interestingly, the lengths of polymers changed with changing pH. RimK also exhibited 86% activity after incubation at 55°C for 15 min, thus showing thermal stability. Furthermore, peptide elongation seemed to be catalyzed at the C terminus in a stepwise manner. Although RimK showed strict substrate specificity toward Glu, it also used, to a small extent, other amino acids as C-terminal substrates and synthesized heteropeptides. In addition, RimK-catalyzed modification of ribosomal protein S6 was confirmed. The number of Glu residues added to the protein varied with pH and was largest at pH 9.5.

  7. Retention behaviour of proteins on poly(vinylimidazole)-copper(II) complexes supported on silica: application to the fractionation of desialylated human alpha 1-acid glycoprotein variants.

    Science.gov (United States)

    Millot, M C; Hervé, F; Sébille, B

    1995-02-03

    The retention behaviour of various amino acids, peptides and proteins on poly(vinylimidazole)-Cu(II) complexes supported on silica was investigated. Free amino acids and peptides containing one histidine and in some instances one additional tryptophan residue in their primary structure were found to elute from the supports only after addition of a competing complexing agent to the mobile phase. However, the results obtained the proteins containing metal binding groups suggested that, in addition to the presence of donor-acceptor interactions between the macromolecules and the immobilized metal, other additional (essentially ionic and/or hydrophobic) interactions took place between the proteins and the surrounding of the metal. When donor-acceptor interactions were predominant, proteins were strongly adsorbed on the stationary phase and their elution required the addition of a competing complexing agent in the mobile phase. However, when the binding between the proteins and the supports via donor-acceptor interactions was less favourable, proteins were eluted from the columns without the addition of a competing agent in the mobile phase. With respect to the binding of these proteins, ionic and/or hydrophobic interactions were no longer negligible during the chromatographic process and the retention of the macromolecules by the stationary phase depended on the elution conditions (ionic strength, pH, etc.). These supports were used in the fractionation of the three main genetic variants of desialylated alpha 1-acid glycoprotein.

  8. Effect of the secondary structure of carbohydrate residues of alpha 1-acid glycoprotein (orosomucoid) on the local dynamics of Trp residues.

    Science.gov (United States)

    Albani, Jihad René

    2004-01-01

    We studied in this work the relation between the secondary structure of the carbohydrate residues of alpha1-acid glycoprotein and the local motions of Trp residues of the protein. We measured for this purpose the fluorescence emission intensity and anisotropy of the Trp residues between -46 and +30 degrees of the sialylated and asialylated protein. Our results indicate that, in both forms, the global profile of the emission intensity with temperature shows that Trp residues display static and collisional interaction with the neighboring amino acids. However, the profile of the asialylated form is more structured than that observed for the sialylated protein. The Y-plot analysis of the emission-anisotropy results indicated that the frictional resistance to rotation of the surface Trp residue is less important in the sialylated protein than in the asialylated form. This result is in good agreement with the fact that, in the asialylated conformation, the carbohydrate residues are closer to the protein surface than in the sialylated form, ther