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Sample records for induces early protection

  1. Anthracycline-induced cardiotoxicity, a pathophysiology based approach for early detection and protective strategies

    NARCIS (Netherlands)

    Broeyer, Frederik Jan Ferdinand

    2012-01-01

    In this thesis the development of a pathophysiology-based method for the early evaluation of anthracycline-induced cardiotoxicity was described. We evaluated a comprehensive array of biomarkers, representing several aspects of anthracycline-induced cardiotoxicity, including cardiac injury and

  2. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

  3. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

    Science.gov (United States)

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

    2015-10-01

    Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Specific synbiotics in early life protect against diet-induced obesity in adult mice

    NARCIS (Netherlands)

    Mischke, Mona; Arora, Tulika; Tims, Sebastian; Engels, Eefje; Sommer, Nina; Limpt, van Kees; Baars, Annemarie; Oozeer, Raish; Oosting, Annemarie; Bäckhed, Fredrik; Knol, Jan

    2018-01-01

    Aims: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life

  5. Specific synbiotics in early life protect against diet-induced obesity in adult mice

    DEFF Research Database (Denmark)

    Mischke, Mona; Arora, Tulika; Tims, Sebastian

    2018-01-01

    AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life a...... as preventive measure to ameliorate obesity risk and improve metabolic health throughout life....

  6. Curcumin Protects against UVB-Induced Skin Cancers in SKH-1 Hairless Mouse: Analysis of Early Molecular Markers in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Kuen-Daw Tsai

    2012-01-01

    Full Text Available Curcumin (CUR has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm2 twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm2 resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2, prostaglandin E2 (PGE2, and nitric oxide (NO levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.

  7. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

    Science.gov (United States)

    Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

    2005-02-01

    Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

  8. Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

    Science.gov (United States)

    Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

    2016-05-01

    Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

  9. TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts.

    Science.gov (United States)

    Leduc, Chloe; Sobilo, Lauren; Toumi, Hechmi; Mondon, Philippe; Lespessailles, Eric; Ossant, Fédéric; Kurfurst, Robin; Pichon, Chantal

    2016-06-01

    Transforming growth factor beta inducible early gene-1 (TIEG-1), a member of the Krüppel-like factor, was identified as a primary response gene for TGF-β. The role of TIEG-1 in skin repair has been mainly addressed in vivo on TIEG-1 null mice model and the mechanism remains unexplored. We investigated the modulation of TIEG-1 expression in normal human skin fibroblasts by either down-expressing or overexpressing the gene. We evaluated reactive oxygen species production and the cell viability of treated cells. The effect of TIEG-1 overexpression was monitored by wound healing assay and immunofluorescence staining of actin fibers organization and alpha-smooth muscle actin (α-SMA). Western blots were carried out to identify the level of expression or phosphorylation of key proteins such as cofilin, Rho GTPases, and p38 mitogen-activated protein kinase (p38 MAPK). TIEG-1 down-regulation had a deleterious effect on the cell viability. It was significantly reduced (65±5%) and exposure to ultraviolet further increased this effect (47±3%). By contrast, cells overexpressing TIEG-1 had a reduced reactive oxygen species production (75%) compared to control and mock-transfected cells. This overexpression also resulted in formation of actin stress fibers and increased α-SMA expression and an enhanced wound healing feature. RhoB GTPase was upregulated and phosphorylation of cofilin and p38 MAPK was observed. TIEG-1 overexpression in normal human skin fibroblasts results in improved resistance to oxidative stress, myofibroblast-like conversion that involved RhoB signaling pathway with cofilin and p38 MAPK proteins activation. This study enlightens the role of TIEG-1 role in skin biology. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Early life DNA vaccination with the H gene of Canine distemper virus induces robust protection against distemper

    DEFF Research Database (Denmark)

    Jensen, Trine Hammer; Nielsen, Line; Aasted, Bent

    2009-01-01

    Young mink kits (n = 8)were vaccinated withDNA plasmids encoding the viral haemagglutinin protein (H) of a vaccine strain of Canine distemper virus (CDV). Virus neutralising (VN) antibodieswere induced after 2 immunisations and after the third immunisation all kits had high VN antibody titres...

  11. δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

    Science.gov (United States)

    Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

    2017-01-01

    Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles

    2014-01-01

    Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494

  13. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

    2014-02-01

    Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

  14. Early diagnosis of dementia and protection

    International Nuclear Information System (INIS)

    Mizuno, Toshiki

    2010-01-01

    Mild cognitive impairment (MCI) refers to the transitional state between the normal elderly and dementia. This concept accelerated many clinical, epidemiological and neuroimaging research in recent 10 years about an early stage of dementia. These studies have approved a significance of this concept and MCI have been classified into subtypes, including prodromal forms of a variety of dementias. An algorithm is proposed to assist the clinician in subclassifying subjects into the various types of MCI, but new several concepts, such as vascular cognitive impairment, still confused clinicians. Therefore, definition and diagnostic procedure for MCI were discussed in this review. Several population-based studies as well as Alzheimer's Disease Neuroimaging Initiative (ADNI) study have documented a higher rate of progression to Alzheimer's disease in individuals diagnosed with MCI. Progression factors, including neuroimaging and vascular risk factors are also discussed. Vascular risk factors, such as hypertension, hyperlipemia and diabetes mellitus can be modulated by food, life style and treatment. The recent clinical trials for protective cognition using anti- hypertensive medication as well as statin is discussed. (author)

  15. Lithium protects ethanol-induced neuronal apoptosis

    International Nuclear Information System (INIS)

    Zhong Jin; Yang Xianlin; Yao Weiguo; Lee Weihua

    2006-01-01

    Lithium is widely used for the treatment of bipolar disorder. Recent studies have demonstrated its neuroprotective effect. Ethanol is a potent neurotoxin that is particularly harmful to the developing nervous system. In this study, we evaluated lithium's neuroprotection against ethanol-induced apoptosis. Transient exposure of infant mice to ethanol caused apoptotic cell death in brain, which was prevented significantly by administering a low dose of lithium 15 min later. In cultured cerebellar granule neurons, ethanol-induced apoptosis and activation of caspase-3/9, both of which were prevented by lithium. However, lithium's protection is not mediated by its commonly known inhibition of glycogen synthase3β, because neither ethanol nor lithium has significant effects on the phosphorylation of Akt (ser473) or GSK3β (ser9). In addition, the selective GSK-3β inhibitor SB-415286 was unable to prevent ethanol-induced apoptosis. These data suggest lithium may be used as a potential preventive measure for ethanol-induced neurological deficits

  16. Liv. 52 protection against radiation induced lesions in mammalian liver

    International Nuclear Information System (INIS)

    Saini, M.R.; Saini, N.

    1985-01-01

    Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of 60 Co gamma radiation. It was found that the drug protected the organ against radiation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nulei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv. 52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems that the drug may act as detoxicating agent. (author)

  17. Protection against Radiotherapy-Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Susan Hall

    2016-07-01

    Full Text Available Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.

  18. Early stage beneficial effects of cathodic protection in concrete structures

    NARCIS (Netherlands)

    Polder, R.B.; Peelen, W.H.A.; Neeft, E.A.C.; Stoop, B.T.J.

    2010-01-01

    Over the last 25 years, cathodic protection (CP) of reinforced concrete structures suffering from chloride induced reinforcement corrosion has shown to be successful and durable. CP current causes steel polarisation, electrochemical reactions and ion transport in the concrete. CP systems are

  19. Zinc-induced protection against cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Early, J.L.; Schnell, R.C.

    1978-02-01

    Pretreatment of male rats with cadmium acetate potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic microsomal drug metabolism. Pretreatment of rats with zinc acetate protects against these alterations in drug action elicited by cadmium.

  20. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

    Directory of Open Access Journals (Sweden)

    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  1. Protective Effect of Vitamin E on Nicotine Induced Reproductive ...

    African Journals Online (AJOL)

    Protective Effect of Vitamin E on Nicotine Induced Reproductive Toxicity in ... The health implications of cigarette smoking and ..... toxic byproducts of many metabolic processes in ... Male infertility, clinical ... rats: A possible role of cessation.

  2. Protection of swimming-induced oxidative stress in some vital ...

    African Journals Online (AJOL)

    Protection of swimming-induced oxidative stress in some vital organs by the treatment of composite extract of Withania somnifera, Ocimum sanctum and Zingiber officinalis in male rat. D Misra, B Maiti, D Ghosh ...

  3. SOCIAL PROTECTION – FROM EARLY HEBREW CULTURE TO CONTEMPORARY CIVILIZATION

    Directory of Open Access Journals (Sweden)

    Dan CONSTANTINESCU

    2014-12-01

    Full Text Available Without the slightest exaggeration we can say that in ancient Israel a complex system of social security was regulated. If that system worked as depicted by the words of Moses and its efficiency are altogether other problems that can make the topic of new research. The disadvantaged categories the Old Testament refers to are not basically different from the persons that make today’s social politics topic, which are: the poor, orphans, widows, emigrants and the sick. Besides, a pericope through Deuteronomy bears the name The Rights of the foreigner, the orphan and widow. It is worth noting that in the Biblical text, the issue of protecting the disadvantaged transcends historical eras. It is found, thus, in the lamentations of the rightful Job, in the thoughts of Solomon and even in the words of our Savior. An everlasting issue to solve which modern approaches should not exclude, in our opinion, is the perennial parts of early Hebrew culture.

  4. Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells

    International Nuclear Information System (INIS)

    Ronald Sluyter; Kylie S Yuen; Gary M Halliday

    2001-01-01

    There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naive recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed-type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR-induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR-induced tumours if stimulated to migrate from the skin. Copyright (2001) Australasian Society of Immunology Inc

  5. Protection of betulin against cadmium-induced apoptosis in hepatoma cells

    International Nuclear Information System (INIS)

    Oh, Seon-Hee; Choi, Jeong-Eun; Lim, Sung-Chul

    2006-01-01

    The protective effects of betulin (BT) against cadmium (Cd)-induced cytotoxicity have been previously reported. However, the mechanisms responsible for these protective effects are unclear. Therefore, this study investigated the mechanisms responsible for the protection of BT against Cd-induced cytotoxicity in human hepatoma cell lines. The protection of BT against Cd cytotoxicity was more effective in the HepG2 than in the Hep3B cells. The protection of BT on Cd-induced cytotoxicity in the HepG2 cells appeared to be related to the inhibition of apoptosis, as determined by PI staining and DNA fragmentation analysis. The anti-apoptosis exerted by BT involved the blocking of Cd-induced reactive oxygen species (ROS) generation, the abrogation of the Cd-induced Fas upregulation, the blocking of caspase-8-dependent Bid activation, and subsequent inhibition of mitochondrial pathway. The BT pretreatment did not affect the p21 and p53 expression levels, when compared with those of the treated cells with Cd alone. BT induced the transient S phase arrest at an early stage and the G /G 1 arrest at a relatively late stage, but it did not observe the sub-G1 apoptotic peak. In the Hep3B cells, Cd did not induce ROS generation. The BT pretreatment partially inhibited the Cd-induced apoptosis, which was related with the incomplete blockage in caspase-9 or -3 activation, as well as in Bax activation. Taken together, it was found that Cd can induce apoptosis via the Fas-dependent and -independent apoptosis pathways. However, the observed protective effects of BT were clearly more sensitive to Fas-expressing HepG2 cells than to Fas-deficient Hep3B cells

  6. Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis

    Science.gov (United States)

    Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.

    2014-01-01

    The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

  7. Reduction of radiation-induced early skin damage (mouse foot) by 0-(β-hydroxyaethyl)-rutoside

    International Nuclear Information System (INIS)

    Fritz-Niggli, H.; Froehlich, E.

    1980-01-01

    The effect of a bioflavonoid, 0-(β-hydroxyethyl)-rutoside (HR) on early radiation-induced skin damage was examined, using the mouse foot system; the response to radiation is not species specific and comparison with the clinical situation is therefore possible. The aim was to see whether HR, which is highly effective in protecting against late damage, is also able to reduce early effects. Early reactions were considered to be erythema, swelling and ulceration and occurring up to 30 days after irradiation. It was found that HR significantly reduces early damage, both after a single dose and after fractionated irradiation with low doses. A single pre-treatment dose of HR and pre-treatment together with 30 days post-treatment administration were both found to be effective. The protective effect became more marked with increasing radiation dose (single irradiation). Reduction of late effects is produced iptimally by an interval of 0.25 hours between application of HR and irradiation, and this is also true for early skin damage. The early effects are partly reversible, but there is possibly an interesting correlation between these and irreversible late effects (such as loss of toes); a similar mechanism, presumably affecting the vascular system, may therefore be postulated. The protective action of this well tolesated, highly effective substance, which apparently protects normal tissues from early and late injury, is discussed. (orig.) [de

  8. Protective Mechanisms of Nitrone Antioxidants in Kanic Acid Induced Neurodegeneration

    Science.gov (United States)

    2004-01-01

    Shin, E.J., Suh, J.H., Floyd, R.A., Bing, G. (1999) Protection of methamphetamine nigrostriatal toxicity by dietary selenium. Brain Res. 851:76-86...HC, and Bing, GY. (2004) Interleukin-10 protects against lipopolysaccharide-mediated neurotoxicity in substantia nigra Neurosci. Abstr. 29:677.18. 71...2004) Roles of the cyclooxygenase-2 and oxidative stress in the methamphetamine - induced neurotoxicity Neurosci. Abstr. 29:235.4.

  9. Management of drug-induced hyperbilirubinaemia in early pregnancy

    African Journals Online (AJOL)

    perinatal outcomes because of the increased risks of preterm delivery and ... induced hepatotoxicity in early pregnancy. ... for threatened abortion since the 6th week. Her past and ... gene mutations, a disease complicated by unconjugated.

  10. Ethanol Induced Urine Acidification is Related with Early Acetaldehyde Concentration

    Directory of Open Access Journals (Sweden)

    Soon Kil Kwon

    2014-06-01

    Conclusion: In conclusion, urine acidification after ethanol ingestion is related with serum acetaldehyde concentration. Early elevation of acetaldhyde could induce urine acidification, but the urine pH was elevated after a few hours, that might make prolonged acidemia.

  11. Rodent malaria: BCG-induced protection and immunosuppression

    International Nuclear Information System (INIS)

    Smrkovski, L.L.; Strickland, G.T.

    1978-01-01

    One dose of 10 7 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10 4 thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge

  12. Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

    Science.gov (United States)

    Diaz-San Segundo, Fayna; Dias, Camila C. A.; Moraes, Mauro P.; Weiss, Marcelo; Perez-Martin, Eva; Owens, Gary; Custer, Max; Kamrud, Kurt; de los Santos, Teresa

    2013-01-01

    We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 107 or 108 infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV. PMID:23468490

  13. Protection of power transformers against geomagnetically induced currents

    Directory of Open Access Journals (Sweden)

    Gurevich Vladimir

    2011-01-01

    Full Text Available The article examines the problem of saturation and failure of power transformers under geomagnetically induced currents and currents of the E3 component of high-altitude nuclear explosions. It also describes a special protective relay reacting on DC component in the transformer neutral current.

  14. Short day photoperiod protects against acetaminophen-induced ...

    African Journals Online (AJOL)

    Prof. Ogunji

    blood was collected by cardiac puncture for the estimation of liver enzymes activities. Liver ... revealed the protective effects of short photoperiod against acetaminophen-induced hepatotoxicity and lipid .... homogenized in ice cold KCl (100mM) containing. 0.003M ... This was followed by the addition of 1.0ml water and 5.0ml ...

  15. Protective effect of vanillic acid on ovariectomy-induced ...

    African Journals Online (AJOL)

    Background: The need for an anti-osteoporotic agent is in high demand since osteoporosis contributes to high rates of disability or impairment (high osteoporotic fracture), morbidity and mortality. Hence, the present study is designed to evaluate the protective effects of vanillic acid (VA) against bilateral ovariectomy-induced ...

  16. Strategic Capacity Rationing to Induce Early Purchases

    OpenAIRE

    Qian Liu; Garrett J. van Ryzin

    2008-01-01

    Dynamic pricing offers the potential to increase revenues. At the same time, it creates an incentive for customers to strategize over the timing of their purchases. A firm should ideally account for this behavior when making its pricing and stocking decisions. In particular, we investigate whether it is optimal for a firm to create rationing risk by deliberately understocking products. Then, the resulting threat of shortages creates an incentive for customers to purchase early at higher price...

  17. Radiation induced early maturing mutants in barley

    International Nuclear Information System (INIS)

    Kumar, R.; Chauhan, S.V.S.; Sharma, R.P.

    1978-01-01

    In M 2 generation, two early maturing plants were screened from a single spike progeny of a plant obtained from 20 kR of gamma-ray irradiation of a six-rowed barley (Hordeum vulgare L. var. Jyoti). Their true breeding nature was confirmed in M 3 generation. These mutants flower and mature 38 and 22 days earlier than those of control. (auth.)

  18. Protective effect of turnip root ethanolic extract on early diabetic nephropathy in the rats

    Directory of Open Access Journals (Sweden)

    Bahram Amouoghli-Tabrizi

    2011-11-01

    Full Text Available Background: Diabetes mellitus is a metabolic disorder and one of its most important consequences is renal insufficiency. A multitude of herbs has been described for the treatment of diabetes mellitus. The aim of present study was to assess the protective effect of turnip root ethanolic extract (TREE on early nephropathy in alloxan-induced diabetic rats.Materials and Method: Eighty male Wistar rats were randomly allocated into 4 equal groups including: healthy rats, normal healthy rats receiving TREE, diabetic rats and diabetic rats receiving TREE. Diabetes was induced by a single injection of alloxan (120 mg/kg; i.p. The extract (200 mg/kg was gavaged to TREE treatment groups daily for 8 weeks. At the end of experiment; serum levels of urea, uric acid and creatinine were assessed. The lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS, and activities of superoxide dismutase, catalase and glutathione peroxidase were measured in the renal tissue. Finally, the biochemical findings were matched with histopathological verification. Statistically, the quantitative data obtained, compared among the groups by one-way analysis of variance followed by Tukey post-test. Statistical significance was considered at p<0.05.Results: In the diabetic rats, TREE significantly decreased the levels of serum biomarkers of renal injury. Furthermore, TREE significantly decreased the lipid peroxidation and elevated the decreased levels of antioxidant enzymes in diabetic rats. Histopathological findings were in agreement with the biochemical findings.Conclusion: TREE has protective effect on early diabetic nephropathy in the rats with experimentally induced diabetes

  19. Induced hypernatraemia is protective in acute lung injury.

    Science.gov (United States)

    Bihari, Shailesh; Dixon, Dani-Louise; Lawrence, Mark D; Bersten, Andrew D

    2016-06-15

    Sucrose induced hyperosmolarity is lung protective but the safety of administering hyperosmolar sucrose in patients is unknown. Hypertonic saline is commonly used to produce hyperosmolarity aimed at reducing intra cranial pressure in patients with intracranial pathology. Therefore we studied the protective effects of 20% saline in a lipopolysaccharide lung injury rat model. 20% saline was also compared with other commonly used fluids. Following lipopolysaccharide-induced acute lung injury, male Sprague Dawley rats received either 20% hypertonic saline, 0.9% saline, 4% albumin, 20% albumin, 5% glucose or 20% albumin with 5% glucose, i.v. During 2h of non-injurious mechanical ventilation parameters of acute lung injury were assessed. Hypertonic saline resulted in hypernatraemia (160 (1) mmol/l, mean (SD)) maintained through 2h of ventilation, and in amelioration of lung oedema, myeloperoxidase, bronchoalveolar cell infiltrate, total soluble protein and inflammatory cytokines, and lung histological injury score, compared with positive control and all other fluids (p ≤ 0.001). Lung physiology was maintained (conserved PaO2, elastance), associated with preservation of alveolar surfactant (p ≤ 0.0001). Independent of fluid or sodium load, induced hypernatraemia is lung protective in lipopolysaccharide-induced acute lung injury. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  1. Activation of Nrf2 protects against triptolide-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Jia Li

    Full Text Available Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF, has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2 in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN, attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

  2. Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Blanca Humanes

    2015-01-01

    Full Text Available Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs. Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs.

  3. Early haemorrhage control and management of trauma-induced coagulopathy

    DEFF Research Database (Denmark)

    Stensballe, Jakob; Henriksen, Hanne H; Johansson, Pär I

    2017-01-01

    of trauma resuscitation using a ratio-driven strategy aiming at 1:1:1 of red blood cells, plasma and platelets while applying goal-directed therapy early and repeatedly to control trauma-induced coagulopathy. SUMMARY: Trauma resuscitation should focus on early goal-directed therapy with use of viscoelastic...... haemostatic assays while initially applying a ratio 1:1:1 driven transfusion therapy (with red blood cells, plasma and platelets) in order to sustain normal haemostasis and control further bleeding....

  4. Rhizobacterially induced protection of watermelon against Didymella bryoniae.

    Science.gov (United States)

    Nga, N T T; Giau, N T; Long, N T; Lübeck, M; Shetty, N P; de Neergaard, E; Thuy, T T T; Kim, P V; Jørgensen, H J L

    2010-08-01

    To identify rhizobacteria from the Mekong Delta of Vietnam, which can systemically protect watermelon against Didymella bryoniae and elucidate the mechanisms involved in the protection conferred by isolate Pseudomonas aeruginosa 23(1-1). Bacteria were isolated from watermelon roots and their antagonistic ability tested in vitro. Of 190 strains, 68 were able to inhibit D. bryoniae by production of antibiotics. Four strains were able to reduce foliar infection by D. bryoniae when applied to watermelon seeds before sowing. Strain Ps. aeruginosa 23(1-1) was chosen for investigations of the mechanisms involved in protection and ability to control disease under field conditions. In the field, the bacterium was able to significantly reduce disease in two consecutive seasons and increase yield. Furthermore, it colonized watermelon plants endophytically, with higher numbers in plants infected by D. bryoniae than in noninoculated plants. To elucidate the mechanisms involved in protection, the infection biology of the pathogen was studied in bacterially treated and control plants. Pseudomonas aeruginosa 23(1-1) treatment inhibited pathogen penetration and this was associated with hydrogen peroxide accumulation, increased peroxidase activity and occurrence of new peroxidase isoforms, thus indicating that resistance was induced. The endophytic bacterium Ps. aeruginosa 23(1-1) can control D. bryoniae in watermelon by antibiosis and induced resistance under greenhouse and field conditions. These findings suggest that rhizobacteria from native soils in Vietnam can be used to control gummy stem blight of watermelon through various mechanisms including induction of resistance.

  5. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

    2013-09-27

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  6. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    International Nuclear Information System (INIS)

    Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

    2013-01-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage

  7. Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity*

    Science.gov (United States)

    Björkblom, Benny; Adilbayeva, Altynai; Maple-Grødem, Jodi; Piston, Dominik; Ökvist, Mats; Xu, Xiang Ming; Brede, Cato; Larsen, Jan Petter; Møller, Simon Geir

    2013-01-01

    The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional non-motor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD. PMID:23792957

  8. Protection against cyanide-induced convulsions with alpha-ketoglutarate.

    Science.gov (United States)

    Yamamoto, H

    1990-04-30

    Protection against convulsions induced by cyanide was observed after treatment with alpha-ketoglutarate, either alone or in combination with sodium thiosulfate, a classical antagonist for cyanide intoxication. However, sodium thiosulfate alone did not protect against cyanide (30 mg/kg)-induced convulsions. gamma-Aminobutyric acid (GABA) levels in brain were decreased by 31% in KCN-treated mice exhibiting convulsions. The combined administration of alpha-ketoglutarate and sodium thiosulfate completely abolished the decrease of GABA levels induced by cyanide. Furthermore, sodium thiosulfate alone also completely abolished the decrease of GABA levels. These results suggest that the depletion of brain GABA levels may not directly contribute to the development of convulsions induced by cyanide. On the other hand, cyanide increased calcium levels by 32% in brain crude mitochondrial fractions in mice with convulsions. The increased calcium levels were completely abolished by the combined administration of alpha-ketoglutarate and sodium thiosulfate, but not affected by sodium thiosulfate alone. These findings support the hypothesis proposed by Johnson et al. (Toxicol. Appl. Pharmacol., 84 (1986) 464) and Robinson et al. (Toxicology, 35 (1985) 59) that calcium may play an important role in mediating cyanide neurotoxicity.

  9. Quercitrin protects skin from UVB-induced oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  10. Quercitrin protects skin from UVB-induced oxidative damage

    International Nuclear Information System (INIS)

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-01-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries

  11. Suramin protects from cisplatin-induced acute kidney injury

    Science.gov (United States)

    Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

    2015-01-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

  12. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

    Science.gov (United States)

    Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

    2006-06-15

    Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

  13. Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

    International Nuclear Information System (INIS)

    Cotrim, Ana P.; Yoshikawa, Masanobu; Sunshine, Abraham N.; Zheng Changyu; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B.; Baum, Bruce J.

    2012-01-01

    Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. Methods and Materials: Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

  14. Protective Effect of HSP25 on Radiation Induced Tissue Damage

    International Nuclear Information System (INIS)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Bae, Sang-Woo; Lee, Yun-Sil; Kim, Sung Ho

    2007-01-01

    Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. HSP25/27 has been suggested to protect cells against apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs. And several mechanisms have been proposed to account for HSP27-mediated apoptotic protection. However radioprotective effect of HSP25/27 in vivo system has not yet been evaluated. The aim of this study was to evaluate the potential of exogenous HSP25 expression, as delivered by adenoviral vectors, to protect animal from radiation induced tissue damage

  15. Parametric analysis of protective grid flow induced vibration

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jooyoung; Eom, Kyongbo; Jeon, Sangyoun; Suh, Jungmin [KEPCO NF Co., Daejeon (Korea, Republic of)

    2012-10-15

    Protective grid (P-grid) flow-induced vibration in a nuclear power reactor is one of the critical factors for the mechanical integrity of a nuclear fuel. The P-grid is located at the lower most position above the bottom nozzle of the nuclear fuel as shown in Fig. 1, and it is required for not only filtering debris, but also supporting fuel rods. On the other hand, P-grid working conditions installed in a nuclear fuel in a reactor are severe in terms of flow speed, temperature and pressure. Considering such a severe condition of P-grid's functional performance in working environment, excessive vibration could be developed. Furthermore, if the P-grid is exposed to high levels of excessive vibration over a long period of time, fatigue failure could be unavoidable. Therefore, it is important to reduce excessive vibration while maintaining P-grid's own functional performance. KEPCO Nuclear Fuel has developed a test facility - Investigation Flow-induced Vibration (INFINIT) - to study flow-induced vibration caused by flowing coolant at various flow rates. To investigate specific relationships between configuration of P-grid and flow-induced vibration characteristics, several types of the P-grids were tested in INFINIT facility. And, based on the test results through parametric studies, the flow-induced vibration characteristics could be analyzed, and critical design parameters were found.

  16. Protective Effects of Edaravone against Methamphetamine-Induced cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Motahareh Koohsari

    Full Text Available ABSTRACT Methamphetamine (METH is widely abused in worldwide. METH use could damage the dopaminergic system and induce cardiotoxicity via oxidative stress and mitochondrial dysfunction. Edaravone, a sedative-hypnotic agent, is known for it's antioxidant properties. In this study we used edaravone for attenuating of METH-induced cardiotoxicity in rats. The groups (six rats in each group were as follows: control, METH (5 mg/kg IP and edaravone (5, 10 and 20 mg/kg, IP was administered 30 min before METH. After 24 hours, animals were killed, heart tissue was separated and mitochondrial fraction was isolated and oxidative stress markers were measured. Edaravone significantly (p<0.05 protected the heart against lipid peroxidation by inhibition of reactive oxygen species (ROS formation. Edaravone also significantly (p<0.05 increased the levels of heart glutathione (GSH. METH administration significantly (p<0.05 disrupted mitochondrial function that edaravone pre-treatment significantly (p<0.05 inhibited METH-induced mitochondrial dysfunction. Protein carbonyl level also increased after METH exposure, but was significantly (p<0.05 decreased with edaravone pre-treatment. These results suggested that edaravone is able to inhibition of METH-induced oxidative stress and mitochondrial dysfunction and subsequently METH-induced cardiotoxicity. Therefore, the effectiveness of this antioxidant should be evaluated for the treatment of METH toxicity and cardio degenerative disease.

  17. Spasm induced by protection balloon during carotid artery stenting

    International Nuclear Information System (INIS)

    Tsutsumi, Masanori; Kazekawa, Kiyoshi; Onizuka, Masanari

    2007-01-01

    The PercuSurge system is a distal balloon embolic protection device used for carotid artery stenting (CAS). We performed a retrospective study on the prognosis and clinical effects of spasms induced by the PercuSurge GuardWire system (PercuSurge-induced spasm). We performed CAS in 118 carotid stenoses using the PercuSurge system. Of the 118 procedures, 31 (26.3%) of the patients experienced PercuSurge-induced spasm, and all underwent postoperative follow-up studies by cerebral angiography and antiplatelet treatment. On follow-up angiograms obtained a mean of 5.2 months (range 3-10 months) after CAS, all 31 PercuSurge-induced spasms had disappeared, and no delayed stenosis was found at the sites where the spasms had occurred. No ischemic events due to the spasms occurred during a mean follow-up of 13 months (range 3-32 months). In the hands of physicians experienced in endovascular surgery, CAS using the PercuSurge system is a safe method with which to treat patients with carotid stenosis. Our study demonstrated that PercuSurge-induced spasms had no morphological or clinical adverse effects. (author)

  18. The protective effect of ebselen on radiocontrast-induced nephrotoxicity.

    Science.gov (United States)

    Ozgur, Tumay; Tutanc, Murat; Zararsiz, Ismail; Motor, Sedat; Ozturk, Oktay Hasan; Yaldiz, Mehmet; Kurtgoz, Ozgur Yildirim

    2012-01-01

    Radiocontrast-induced nephropathy has become one of the most important causes of renal acute failure. The most effective management of reducing the incidence of contrast nephropathy is to understand and prevent its causes. We aimed to investigate the protective role of ebselen against radiocontrast-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Albino Wistar rats were randomly separated into four groups. The Group 1 rats were treated with sodium chloride as the control group, Group 2 with radiocontrast, Group 3 with radiocontrast plus ebselen, and Group 4 with ebselen alone. After 24 h, the animals over the experimental period were euthanized and blood samples were analyzed for blood urea nitrogen (BUN) and serum creatinine (Cr) levels. Kidney sections were analyzed for malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as histopathological changes. In the radiocontrast group, BUN, MDA, and GSH-Px levels increased while SOD activity decreased compared with the control group. These decays were improved by ebselen administration in the radiocontrast group. Significant histological deteriorations were observed in the radiocontrast group. We noted improvement in the histologic findings with ebselen administration. These results indicate that ebselen might produce a protective mechanism against radiocontrast-induced nephrotoxicity.

  19. Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

    Science.gov (United States)

    Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

    2015-04-01

    Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

  20. Immunity induced shortly after DNA vaccination of rainbow trout against rhabdoviruses protects against heterologous virus but not against bacterial pathogens

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja

    2002-01-01

    whereas no increased survival was found upon challenge with bacterial pathogens. Within two months after vaccination, the cross-protection disappeared while the specific immunity to homologous virus remained high. The early immunity induced by the DNA vaccines thus appeared to involve short-lived non......It was recently reported that DNA vaccination of rainbow trout fingerlings against viral hemorrhagic septicaemia virus (VHSV) induced protection within 8 days after intramuscular injection of plasmid DNA. In order to analyse the specificity of this early immunity, fish were vaccinated with plasmid...... DNA encoding the VHSV or the infectious haematopoietic necrosis virus (IHNV) glycoprotein genes and later challenged with homologous or heterologous pathogens. Challenge experiments revealed that immunity established shortly after vaccination was cross-protective between the two viral pathogens...

  1. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    International Nuclear Information System (INIS)

    Vilela, Luciano R.; Gobira, Pedro H.; Viana, Thercia G.; Medeiros, Daniel C.; Ferreira-Vieira, Talita H.; Doria, Juliana G.; Rodrigues, Flávia; Aguiar, Daniele C.; Pereira, Grace S.; Massessini, André R.; Ribeiro, Fabíola M.; Oliveira, Antonio Carlos P. de; Moraes, Marcio F.D.; Moreira, Fabricio A.

    2015-01-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB 1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB 1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis attenuates

  2. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  3. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

    International Nuclear Information System (INIS)

    Oldfield, E.H.; Friedman, R.; Kinsella, T.; Moquin, R.; Olson, J.J.; Orr, K.; DeLuca, A.M.

    1990-01-01

    To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms

  4. Inactivated rotavirus vaccine induces protective immunity in gnotobiotic piglets.

    Science.gov (United States)

    Wang, Yuhuan; Azevedo, Marli; Saif, Linda J; Gentsch, Jon R; Glass, Roger I; Jiang, Baoming

    2010-07-26

    Live oral rotavirus vaccines that are effective in middle and high income countries have been much less immunogenic and effective among infants in resource-limited settings. Several hypotheses might explain this difference, including neutralization of the vaccine by high levels of maternal antibody in serum and breast milk, severe malnutrition, and interference by other flora and viruses in the gut. We have pursued development of an alternative parenteral rotavirus vaccine with the goal of inducing comparable levels of immunogenicity and efficacy in populations throughout the world regardless of their income levels. In the present study, we assessed the immunogenicity and protection of a candidate inactivated rotavirus vaccine (IRV), the human strain CDC-9 (G1P[8]) formulated with aluminum phosphate, against rotavirus infection in gnotobiotic piglets. Three doses of IRV induced high titers of rotavirus-specific IgG and neutralizing activity in the sera of gnotobiotic piglets and protection against shedding of rotavirus antigen following oral challenge with a homologous virulent human strain Wa (G1P[8]). Our findings demonstrate the proof of concept for an IRV in a large animal model and provide evidence and justification for further clinical development as an alternative candidate vaccine. Published by Elsevier Ltd.

  5. Sepsis-induced myocardial dysfunction and myocardial protection from ischemia/reperfusion injury.

    Science.gov (United States)

    McDonough, Kathleen H; Virag, Jitka Ismail

    2006-01-01

    Sepsis, bacteremia and inflammation cause myocardial depression. The mechanism of the dysfunction is not clearly established partly because dysfunction can be elicited by many different mechanisms which can all manifest in disruption of myocardial mechanical function. In addition the models of sepsis and bacteremia and inflammation may vary drastically in the sequence of the coordinated immune response to the inflammatory or septic stimulus. Patterns of cytokine expression can vary as can other responses of the immune system. Patterns of neurohumoral activation in response to the stress of sepsis or bacteremia or inflammation can also vary in both magnitude of response and temporal sequence of response. Stress induced activation of the sympathetic nervous system and humoral responses to stress have a wide range of intensity that can be elicited. The fairly uniform response of the myocardium indicating cardiac dysfunction is surprisingly constant. Systolic performance, as measured by stroke volume or cardiac output and pressure work as estimated by ventricular pressure, are impaired when myocardial contraction is compromised. At times, diastolic function, assessed by ventricular relaxation and filling, is impaired. In addition to the dysfunction that occurs, there is a longer term response of the myocardium to sepsis, and this response is similar to that which is elicited in the heart by multiple brief ischemia/reperfusion episodes and by numerous pharmacological agents as well as heat stress and modified forms of lipopolysaccharide. The myocardium develops protection after an initial stress such that during a second stress, the myocardium does not exhibit as much damage as does a non-protected heart. Many agents can induce this protection which has been termed preconditioning. Both early preconditioning (protection that is measurable min to hours after the initial stimulus) and late preconditioning (protection that is measurable hours to days after the initial

  6. RNase L mediated protection from virus induced demyelination.

    Directory of Open Access Journals (Sweden)

    Derek D C Ireland

    2009-10-01

    Full Text Available IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/- mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/- mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.

  7. Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhang, Hailin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Wang, Xiumei; Wang, Yu; He, Zehong; Yao, Huan

    2016-08-15

    LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10 mg/kg) or DEX (5 mg/kg) at 1 and 12 h before injecting LPS (30 mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72 h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. - Highlights: • Cavidine significantly reduced mortality in mice during 72 h after LPS injection. • Cavidine attenuated histopathological changes in lung, liver and kidney. • Cavidine decreased the level of early inflammatory cytokine TNF-α, IL-6 in LPS- stimulated mice. • Cavidine inhibited late inflammatory cytokine HMGB1 through MAPK pathway.

  8. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Science.gov (United States)

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  9. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    Full Text Available The gut microbiota (GM modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L strain, L. paracasei DSM13434 (L. para or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  10. Protection against radiation-induced performance decrement in mice

    International Nuclear Information System (INIS)

    Mukherjee, S.K.; Pant, Kanchan; Goel, H.C.; Jain, Viney

    1997-01-01

    Recognizing that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, 1 Gy) significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40%). Recovery took place in four days. If diltiazem (7 mg/kg b.w.), a Ca 2+ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated. (author). 23 refs., 2 figs

  11. Thalidomide protects mice against LPS-induced shock

    Directory of Open Access Journals (Sweden)

    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  12. [Clinical study of induced abortion of early-early pregnancy: an analysis of 10, 404 cases].

    Science.gov (United States)

    Kang, Jian; Wang, Xue-fen; Zhang, Li; Liu, Jian-hua

    2012-01-03

    To evaluate the advantages and disadvantages of early-early pregnancy induced abortion (EPIA). A total of 10 404 cases of EPIA performed at our hospital from January 1993 to December 2003 were retrospectively analyzed and compared with 9434 cases of common induced abortion (CIA). The amount of hemorrhage and operative duration, degree of pain, rate of induced-abortion syndrome, rate of incomplete abortion, menstrual changes and post-operative onset of Asherman's syndrome were observed and compared between 2 groups. The average age, ratio of parous cases, ratio of the cases of first-pregnancy induced abortion were not different between 2 groups (P > 0.05). The amount of hemorrhage bleeding ((4.9 ± 3.2) ml), operative duration ((90.3 ± 12.4) s), degree of pain, rate of induced-abortion syndrome, menstrual changes and the rate of Asherman's syndrome in the EPIA group were all significantly less than those in the CIA group (P abortion (0.44%) in the EPIA group was significantly higher than that (0.21%) in the CIA group (P abortion stays high.

  13. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

    Science.gov (United States)

    Khairnar, Vishal; Duhan, Vikas; Maney, Sathish Kumar; Honke, Nadine; Shaabani, Namir; Pandyra, Aleksandra A.; Seifert, Marc; Pozdeev, Vitaly; Xu, Haifeng C.; Sharma, Piyush; Baldin, Fabian; Marquardsen, Florian; Merches, Katja; Lang, Elisabeth; Kirschning, Carsten; Westendorf, Astrid M.; Häussinger, Dieter; Lang, Florian; Dittmer, Ulf; Küppers, Ralf; Recher, Mike; Hardt, Cornelia; Scheffrahn, Inka; Beauchemin, Nicole; Göthert, Joachim R.; Singer, Bernhard B.; Lang, Philipp A.; Lang, Karl S.

    2015-01-01

    B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1−/− mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1−/− mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses. PMID:25692415

  14. Potential protective effect of honey against paracetamol-induced hepatotoxicity.

    Science.gov (United States)

    Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

    2012-11-01

    Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

  15. Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19 Cells

    Directory of Open Access Journals (Sweden)

    Chi-Ming Chan

    2015-03-01

    Full Text Available Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD. Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2 expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.

  16. Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19 Cells

    Science.gov (United States)

    Chan, Chi-Ming; Huang, Cheng-Hua; Li, Hsin-Ju; Hsiao, Chien-Yu; Su, Ching-Chieh; Lee, Pei-Lan; Hung, Chi-Feng

    2015-01-01

    Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD. PMID:25775159

  17. The turmeric protective properties at ethanol-induced behavioral disorders.

    Directory of Open Access Journals (Sweden)

    Goldina I.A.

    2017-03-01

    Full Text Available The aim of the study was to determine the effect of mechanically modified turmeric extract on the parameters of orienting-exploratory behavior in mice with chronic ethanol consumption. Material and methods. Mice behavior was assessed in the "open field" test. In the both control groups the animals received water or 10% ethanol solution; in the test group — turmeric extract in 10% ethanol solution. Amount of blood mononuclear cells, thymocytes, and splenocytes were estimated. Results. Analysis of the behavioral parameters in animals after chronic exposure to ethanol showed suppression of motor and exploratory components of the behavior. In mice that received both ethanol and turmeric extract recorded behavior parameters were significantly higher than in the group of animals who received ethanol only. It was shown that the turmeric extract enhances the amount of blood immune cells. Conclusion. Mechanically modified turmeric extract possesses protective properties against ethanol-induced behavioral disorders.

  18. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

    Directory of Open Access Journals (Sweden)

    Yan-Ren Lin

    2016-01-01

    Full Text Available Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2 were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n=20 and control (normal saline, n=20 groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5 or to culture medium (control. Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p<0.05. In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53 and apoptosis (caspase-3, Bcl-xL markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR. L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5. More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells’ beating function at a low pH level.

  19. C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

    Science.gov (United States)

    Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

    2012-01-01

    Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Transfer of maternal immunity to piglets is involved in early protection against Mycoplasma hyosynoviae infection

    DEFF Research Database (Denmark)

    Lauritsen, Klara Tølbøl; Hagedorn-Olsen, Tine; Jungersen, Gregers

    2017-01-01

    Mycoplasma hyosynoviae causes arthritis in pigs older than 12 weeks. The role of colostrum in protection of piglets against M. hyosynoviae infection is not clear. Our objective was therefore to investigate whether transfer of maternal immunity to piglets was involved in early protection against...... immune response that complements the maternally transferred immune factors. Evident from this study is that the general absence of M. hyosynoviae arthritis in piglets can be ascribed mainly to their immunological status....

  1. Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression

    Directory of Open Access Journals (Sweden)

    Francesco Rusconi

    2018-05-01

    Full Text Available Psychiatric disorders entail maladaptive processes impairing individuals’ ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress—including bullying, mobbing and abuse—, and undergoing economic crisis or chronic illnesses. In the last few years the field of epigenetics promised to understand core mechanisms of gene-environment crosstalk, contributing to get into pathogenic processes of many disorders highly influenced by stressful life conditions. However, still very little is known about mechanisms that tune gene expression to adapt to the external milieu. In this Perspective article, we discuss a set of protective, functionally convergent epigenetic processes induced by acute stress in the rodent hippocampus and devoted to the negative modulation of stress-induced immediate early genes (IEGs transcription, hindering stress-driven morphostructural modifications of corticolimbic circuitry. We also suggest that chronic stress damaging protective epigenetic mechanisms, could bias the functional trajectory of stress-induced neuronal morphostructural modification from adaptive to maladaptive, contributing to the onset of depression in vulnerable individuals. A better understanding of the epigenetic response to stress will be pivotal to new avenues of therapeutic intervention to treat depression, especially in light of limited efficacy of available antidepressant drugs.

  2. Protection from ionizing radiation induced damages by phytoceuticals and nutraceuticals

    International Nuclear Information System (INIS)

    Nair, C.K.K.

    2012-01-01

    Exposure of living systems to ionizing radiation cause a variety of damages to DNA and membranes due to generation of free radicals and reactive oxygen species. The radiation induced lesions in the cellular DNA are mainly strand breaks, damage to sugar moiety, alterations and elimination of bases, cross links of the intra and inter strand type and cross links to proteins while peroxidation of the lipids and oxidation of proteins constitute the major lesions in the membranes. The radioprotectors elicit their action by various mechanisms such as i) by suppressing the formation of reactive species, ii) detoxification of radiation induced species, iii) target stabilization and iv) enhancing the repair and recovery processes. The radioprotective compounds are of importance in medical, industrial, environmental, military and space science applications. Radiation protection might offer a tactical advantage on the battlefield in the event of a nuclear warfare. Radioprotectors might reduce the cancer risk to populations exposed to radiations directly or indirectly through industrial and military applications. The antioxidant and radioprotective properties a few of these agents under in vitro and in vivo conditions in animal models will be discussed

  3. Detection of early caries by laser-induced breakdown spectroscopy

    Science.gov (United States)

    Sasazawa, Shuhei; Kakino, Satoko; Matsuura, Yuji

    2015-07-01

    To improve sensitivity of dental caries detection by laser-induced breakdown spectroscopy (LIBS) analysis, it is proposed to utilize emission peaks in the ultraviolet. We newly focused on zinc whose emission peaks exist in ultraviolet because zinc exists at high concentration in the outer layer of enamel. It was shown that by using ratios between heights of an emission peak of Zn and that of Ca, the detection sensitivity and stability are largely improved. It was also shown that early caries are differentiated from healthy part by properly setting a threshold in the detected ratios. The proposed caries detection system can be applied to dental laser systems such as ones based on Er:YAG-lasers. When ablating early caries part by laser light, the system notices the dentist that the ablation of caries part is finished. We also show the intensity of emission peaks of zinc decreased with ablation with Er:YAG laser light.

  4. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    Science.gov (United States)

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  5. Protection against methanol-induced retinal toxicity by LED photostimulation

    Science.gov (United States)

    Whelan, Harry T.; Wong-Riley, Margaret T. T.; Eells, Janis T.

    2002-06-01

    We have initiated experiments designed to test the hypothesis that 670-nm Light-Emitting Diode (LED) exposure will attenuate formate-induced retinal dysfunction in a rodent model of methanol toxicity. Methanol intoxication produces toxic injury to the retina. The toxic metabolite formed in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit cytochrome oxidase activity. 670-nm LED light has been hypothesized to act by stimulating cytochrome oxidase activity. To test this hypothesis, one group of animals was intoxicated with methanol, a second group was intoxicated with methanol and LED-treated and a third group was untreated. LED treatment (670 nm for 1 min 45 seconds equals 50 mW/cm2, 4 joules/cm2) was administered at 5, 25, and 50 hours after the initial dose of methanol. At 72 hours of methanol intoxication, retinal function was assessed by measurement of ERG responses and retinas were prepared for histologic analysis. ERG responses recorded in methanol-intoxicated animals revealed profound attenuation of both rod-dominated and UV-cone mediated responses. In contrast, methanol- intoxicated animals exposed to LED treatment exhibited a nearly complete recovery of rod-dominated ERG responses and a slight improvement of UV-cone mediated ERG responses. LED treatment also protected the retina against the histopathologic changes produced by formate in methanol intoxication. These data provide evidence that LED phototherapy protects the retina against the cytotoxic actions of formate and are consistent with the hypothesis that LED photostimulation improves mitochondrial respiratory chain function.

  6. Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion

    Directory of Open Access Journals (Sweden)

    Yu Zou

    2017-01-01

    Conclusions: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.

  7. Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth

    Directory of Open Access Journals (Sweden)

    Bikul Das

    2008-10-01

    Full Text Available Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II (cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato platinum(II (carboplatin-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage. Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

  8. Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Shanshan [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 (China); Wang, Jiaxing [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Zhang, Xu; Shi, Ying; Li, Bochuan; Bao, Qiankun [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Pang, Wei [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Ai, Ding [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Zhu, Yi [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); He, Jinlong, E-mail: hejinlong@tmu.edu.cn [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)

    2016-08-19

    Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.

  9. Early-life family structure and microbially induced cancer risk.

    Science.gov (United States)

    Blaser, Martin J; Nomura, Abraham; Lee, James; Stemmerman, Grant N; Perez-Perez, Guillermo I

    2007-01-01

    Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men. We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative), belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0) among those in a sibship of seven or more individuals than in a sibship of between one and three persons. These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

  10. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  11. Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

    Science.gov (United States)

    Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

    2017-07-01

    Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

  12. An induced early mutant in finger millet Eleusin coranaca Gaertn

    International Nuclear Information System (INIS)

    Shivashankar, G.; Kempanna, C.; Viswanatha, S.R.

    1975-01-01

    Among the several collections of ragi (Eleusine coracana. Gaertn.) from all over the world, the strain 'H.E.S.927' has been found to be the highest yielder compared to other cultivars. Mutation studies have been conducted on this variety at Bangalore in India to make it suitable for the rainfall pattern of the ragi tract of the Karnataka state. A mutant induced by gamma radiation at 30 K rad has been stabilized. This mutant is early by 30-35 days with comparatively better straw quality. Various morphological characters concerning the yield and yield attributes and the possibility of exploiting it as a genotype for future breeding work and as a promising variety is discussed. Another promising mutant with earhead measuring 15 cm as against the earhead length of 5 to 10 cm of the cultivated varieties is illustrated. (K.B.)

  13. Functional analysis of chloroplast early light inducible proteins (ELIPs)

    Energy Technology Data Exchange (ETDEWEB)

    Wetzel, Carolyn M

    2005-02-22

    The objectives of this project were to characterize gene expression patterns of early light inducible protein (ELIP) genes in Arabidopsis thaliana and in Lycopersicon esculentum, to identify knock mutants of the 2 ELIP genes in Arabidopsis, and to characterize the effects of the knockouts. Expression in Arabidopsis was studied in response to thylakoid electron transport chain (PETC) capacity, where it was found that there is a signal for expression associated with reduction of the PETC. Expression in response to salt was also studied, with different responses of the two gene copies. Knockout lines for ELIP1 and ELIP2 have been identified and are being characterized. In tomato, it was found that the single-copy ELIP gene is highly expressed in ripening fruit during the chloroplast-to-chromoplast transition. Studies of expression in tomato ripening mutants are ongoing.

  14. Nitric oxide protects macrophages from hydrogen peroxide-induced apoptosis by inducing the formation of catalase.

    Science.gov (United States)

    Yoshioka, Yasuhiro; Kitao, Tatsuya; Kishino, Takashi; Yamamuro, Akiko; Maeda, Sadaaki

    2006-04-15

    We investigated the cytoprotective effect of NO on H2O2-induced cell death in mouse macrophage-like cell line RAW264. H2O2-treated cells showed apoptotic features, such as activation of caspase-9 and caspase-3, nuclear fragmentation, and DNA fragmentation. These apoptotic features were significantly inhibited by pretreatment for 24 h with NO donors, sodium nitroprusside and 1-hydroxy-2-oxo-3,3-bis-(2-aminoethyl)-1-triazene, at a low nontoxic concentration. The cytoprotective effect of NO was abrogated by the catalase inhibitor 3-amino-1,2,4-triazole but was not affected by a glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine. NO donors increased the level of catalase and its activity in a concentration-dependent manner. Cycloheximide, a protein synthesis inhibitor, inhibited both the NO-induced increase in the catalase level and the cytoprotective effect of NO. These results indicate that NO at a low concentration protects macrophages from H2O2-induced apoptosis by inducing the production of catalase.

  15. The ''Uranium Society''. Looking at the early history of radiation protection

    International Nuclear Information System (INIS)

    Nagel, G.

    2000-01-01

    The contribution initially looks at the early days of research activities conducted inter alia under an ''atomic research programme'' of the Third Reich, highlighting essential steps and experiments in the history, the foundation of the 'Uranverein' (uranium society) and the avtivities of the group of scientists around Heisenberg. The author presents information that answers the question of whether and how the scientists in those days have been thinking of adequate protection against harmful and toxic effects of the uranium material they were handling. The first instructions for on-the-job safety and protective measures recommended at the time are reported, and are also illustrated by some pictures. (orig./CB) [de

  16. Determinants of Cancer Early Detection Behaviors:Application of Protection Motivation Theory

    OpenAIRE

    Rahaei, Zohreh; Ghofranipour, Fazlollah; Morowatisharifabad, Mohammad Ali; Mohammadi, Eesa

    2015-01-01

    Background: Cancer is account for 13% of all deaths around the world and is the third cause of mortality in Iran. More than one third of these cases are pre-ventable and about 33% are curable with early detection. The aim of this study was to determine the predictors of cancer early detection (CED) behaviors ap-plying Protection Motivation Theory (PMT). Methods: In this cross-sectional study, cluster sampling method was employed to recruit 260 individuals of above 20 years old in Yazd, Ira...

  17. Early-life family structure and microbially induced cancer risk.

    Directory of Open Access Journals (Sweden)

    Martin J Blaser

    2007-01-01

    Full Text Available Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men.We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative, belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0 among those in a sibship of seven or more individuals than in a sibship of between one and three persons.These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

  18. Protection against {sup 131}I-induced Double Strand DNA Breaks in Thyroid Cells

    Energy Technology Data Exchange (ETDEWEB)

    Hershman, J.M.; Okunyan, A.; Cannon, S.; Hogen, V. [Endocrinology, UCLA-VA, Los Angeles (United States); Rivina, Y. [Radiation Biology, UCLA, Los Angeles (United States)

    2012-07-01

    Radioiodine-131 (I{sup 131}) released from nuclear reactor accidents has dramatically increased the incidence of papillary thyroid cancer in exposed individuals, especially young children. The accepted measure for prevention of radiation-induced thyroid cancer is potassium iodide tablets that contain 100 mg iodide taken daily to block thyroid uptake of I{sup 131}. The deposition of ionizing radiation in cells results in double-strand DNA breaks (DSB) at fragile sites, and this early event can generate oncogenic rearrangements that eventually cause the cancer. We have developed a thyroid cell model to quantify the mitogenic effect of I{sup 131}. I{sup 131} causes double strand DNA breaks in FRTL-5 cells detected by 53BP1 or gamma H2AX and had no effect on cells that do not transport iodide. Perchlorate, iodide, and thiocyanate protect against DSB induced by I{sup 131}. Preincubation with the anion or radioprotective compounds prevents DSB; delayed addition of the anion is much less effective. These data provide a basis for studies of radioprotection against DSB induced by I{sup 131} in animals in order to refine the prevention of thyroid cancer resulting from nuclear fallout

  19. Geldanamycin induces heat shock protein 70 and protects against MPTP-induced dopaminergic neurotoxicity in mice.

    Science.gov (United States)

    Shen, Hai-Ying; He, Jin-Cai; Wang, Yumei; Huang, Qing-Yuan; Chen, Jiang-Fan

    2005-12-02

    As key molecular chaperone proteins, heat shock proteins (HSPs) represent an important cellular protective mechanism against neuronal cell death in various models of neurological disorders. In this study, we investigated the effect as well as the molecular mechanism of geldanamycin (GA), an inhibitor of Hsp90, on 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity, a mouse model of Parkinson disease. Neurochemical analysis showed that pretreatment with GA (via intracerebral ventricular injection 24 h prior to MPTP treatment) increased residual dopamine content and tyrosine hydroxylase immunoreactivity in the striatum 24 h after MPTP treatment. To dissect out the molecular mechanism underlying this neuroprotection, we showed that the GA-mediated protection against MPTP was associated with a reduction of cytosolic Hsp90 and an increase in Hsp70, with no significant changes in Hsp40 and Hsp25 levels. Furthermore, in parallel with the induction of Hsp70, striatal nuclear HSF1 levels and HSF1 binding to heat shock element sites in the Hsp70 promoter were significantly enhanced by the GA pretreatment. Together these results suggested that the molecular cascade leading to the induction of Hsp70 is critical to the neuroprotection afforded by GA against MPTP-induced neurotoxicity in the brain and that pharmacological inhibition of Hsp90 may represent a potential therapeutic strategy for Parkinson disease.

  20. Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats

    Directory of Open Access Journals (Sweden)

    Junfa Wu

    2013-03-01

    Full Text Available Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL and Fluoro-Jade-B staining (F-J-B. Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5, inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5, and increased the expression of Bcl-2 (p < 0.05, n = 5. These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis.

  1. Determinants of Cancer Early Detection Behaviors:Application of Protection Motivation Theory.

    Science.gov (United States)

    Rahaei, Zohreh; Ghofranipour, Fazlollah; Morowatisharifabad, Mohammad Ali; Mohammadi, Eesa

    2015-01-01

    Cancer is account for 13% of all deaths around the world and is the third cause of mortality in Iran. More than one third of these cases are pre-ventable and about 33% are curable with early detection. The aim of this study was to determine the predictors of cancer early detection (CED) behaviors applying Protection Motivation Theory (PMT). In this cross-sectional study, cluster sampling method was employed to recruit 260 individuals of above 20 years old in Yazd, Iran and a researcher designed questionnaire was completed through interviews for each of the respondents. PMT theoretical variables and CED behaviors were the basis of data collection procedure. Participants acquired 64.47% of the protection motivation, 30.97% of the passive and 45.64% of the active behaviors‟ possible scores. Theory constructs predicted 19.8%, 15.6% and 9.6% of the variations for protection motivation, passive and active behavior respectively. Protection motivation was responsible for 3.6% of passive and 8% of active behaviors‟ variations. Considering the scarceness of CED behaviors and the applicability of PMT in predicting these behaviors, utilization of the PMT‟s constructs in any interventional programs to accelerate CED behaviors could be an alternate methodological choice in the cancer control initiatives.

  2. Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

    Science.gov (United States)

    Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

    2013-11-30

    Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Protective effect of edaravone against tobramycin-induced ototoxicity

    NARCIS (Netherlands)

    Asplund, Monika Stenkvist; Lidian, Adnan; Linder, Birgitta; Takumida, Masaya; Anniko, Matti

    2009-01-01

    Conclusion. It is suggested that simultaneous treatment with the radical scavenger edaravone has an effective protective effect against tobramycin ototoxicity in rat. Even if the edaravone treatment is postponed for 7 days, it can still prevent hearing loss, but a 14 day delay cannot protect from

  4. Andrographolide protects against radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Kang Yahui; Wang Jinfeng; Zhang Qu; Huang Guanhong; Ma Jianxin; Yang Baixia; He Xiangfeng; Wang Zhongming

    2014-01-01

    Objective: To investigate the protective effect of andrographolide against radiation-induced lung injury (RILI) in C57BL/6 mice. Methods: Eighty C57BL mice were randomly divided into four groups: un-irradiated and normal saline-treated group (n = 20, control group), un-irradiated and andrographolide-treated group (n = 20, drug group), radiation plus normal saline-treated group (n = 20, radiation group) and radiation plus andrographolide-treated group (n = 20, treatment group). Before radiation, the mice in drug group and treatment group were administered daily via gavage with andrographolide (20 mg·kg -1 ·d -1 )) for 30 d, while the same volume of normal saline solution was given daily in the control and radiation groups. The model of RILI in C57BL mice was established by irradiating whole mouse chest with a single dose of 15 Gy of 6 MV X-rays. The pathological changes of the lung stained with HE/Masson were observed with a light microscope. The transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in serum were examined by enzyme-linked immunosorbent assay. The activities of malondialdehyde (MDA) and superoxide dismutase (SOD) and the content of hydroxyproline in lung tissues were examined by corresponding kits. Results: Compared with radiation group, there was an obvious amelioration in pathological injury of lung tissue in the treatment group. The lung coefficient, the activities of lung tissue MDA, the content of Hyp, the serum content of hydroxide free radical, and the serum levels of TGF-β1 and TNF-α in the treatment group were significantly lower than those in radiation group at 24 th week, (t lung coefficient = 1.60, t MDA = 7.06, t Hyp = 17.44, t TGF-β1 = 16.67, t TNF-α = 14.03, P < 0.05), while slightly higher than those in control group. The activity of SOD was significantly higher in the treatment group than that in radiation group (t = 60.81, P < 0.05), while lower than those in control group and drug group. There were no

  5. Differential Requirements for T Cells in Viruslike Particle- and Rotavirus-Induced Protective Immunity▿

    Science.gov (United States)

    Blutt, Sarah E.; Warfield, Kelly L.; Estes, Mary K.; Conner, Margaret E.

    2008-01-01

    Correlates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered murine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4+ T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered. PMID:18184712

  6. Radiation induced early onset of neuro-cognitive changes

    International Nuclear Information System (INIS)

    Kumar, Mayank; Haridas, Seenu; Gupta, Mamta; Trivedi, Richa; Khushu, Subhash; Manda, Kailash

    2012-01-01

    Exposure to ionizing radiations has been shown to cause many detrimental effects. Primarily, the effects observed are broadly classified into hematopoietic syndrome at lower doses, gastrointestinal syndrome and central nervous system dysfunctions at high doses. However, recent studies reported that even at lower doses, there is an effect seen on the nervous system which can be observed as a decline in cognitive abilities. This has been reported in patients undergoing radiotherapy. The cognitive decline, especially in young patients affects development and has been shown to persist for years after the therapy. Thus, the aim of this study was to study and consolidate the early effects of radiation exposure which result in behavioural alterations and cognitive decline. Since, radiation-induced early changes in behavioural functions are poorly understood, therefore, the present investigation aimed to conceptualize and design behavioural test batteries in order to systematically study the immediate alterations in behavioural function following irradiation with a-rays. The behavioural alterations were correlated to changes in the different area of brain like hippocampus, thalamus, hypothalamus and corpus callosum using Diffusion Tensor Imaging (DTI) studies. Present study reported profound changes in behaviour, as well as alterations in the morphology of the brain tissue as perceived by DTI, 48 hours after exposure to ionizing radiations. These changes need to be correlated and clarified further to understand the mechanisms behind the cognitive dysfunctions occurring immediately after radiation exposure as well as to find out a therapeutic window to counteract or reduce the effect of long term cognitive changes following irradiation. (author)

  7. Study on homologous series of induced early mutants in Indica rice Ⅱ. the relationship between the homologous series of early mutants induced and the ecotype in Indica rice

    International Nuclear Information System (INIS)

    Chen Xiulan; Yang Hefeng; He Zhentian; Han Yuepeng; Liu Xueyu

    2001-01-01

    The induced mutation in light sensitivity of the Indica rice leads to induction of the homologous series of early mutants along with the variation of ecological character and the ecoclimate. The induction of mutants was closely related to the ecotype of Indica rice, the homologous series of early mutants in different level were derived from the different ecotype of the Indica rice, otherwise, the similar homologous series of early mutants were derived from the same ecotypic variety. The induction of the early ecotypic variety derived from the homologous series of early mutants provides the basis and possibility for accelerating the development of the new cultivars. (authors)

  8. Early Leakage Protection System of LPG (Liquefied Petroleum Gas) Based on ATMega 16 Microcontroller

    Science.gov (United States)

    Sriwati; Ikhsan Ilahi, Nur; Musrawati; Baco, Syarifuddin; Suyuti'Andani Achmad, Ansar; Umrianah, Ejah

    2018-04-01

    LPG (Liquefied Petroleum Gas). LPG is a hydrocarbon gas production from refineries and gas refinery with the major components of propane gas (C3H8) and butane (C4H10). Limit flame (Flammable Range) or also called gas with air. Value Lower Explosive Limit (LEL) is the minimum limit of the concentration of fuel vapor in the air which if there is no source of fire, the gas will be burned. While the value of the Upper Explosive Limit (UEL), which limits the maximum concentration of fuel vapor in the air, which if no source of fire, the gas will be burned. Protection system is a defend mechanism of human, equipment, and buildings around the protected area. Goals to be achieved in this research are to design a protection system against the consequences caused by the leakage of LPG gas based on ATmega16 microcontroller. The method used in this research is to reduce the levels of leaked LPG and turned off the power source when the leakage of LPG is on the verge of explosive limit. The design of this protection system works accurately between 200 ppm up to 10000 ppm, which is still below the threshold of explosive. Thus protecting the early result of that will result in the leakage of LPG gas.

  9. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

    2011-12-01

    Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Protective effect of esculentoside A on radiation-induced dermatitis and fibrosis

    International Nuclear Information System (INIS)

    Xiao Zhenyu; Su Ying; Yang Shanmin; Yin Liangjie; Wang Wei; Yi Yanghua; Fenton, Bruce M.; Zhang Lurong; Okunieff, Paul

    2006-01-01

    Purpose: To investigate the effect of esculentoside A (EsA) on radiation-induced cutaneous and fibrovascular toxicity and its possible molecular mechanisms, both in vivo and in vitro. Methods and Materials: Mice received drug intervention 18 hours before 30 Gy to the right hind leg. Alterations in several cytokines expressed in skin tissue 2 days after irradiation were determined by ELISA. Early skin toxicity was evaluated 3 to 4 weeks after irradiation by skin scoring, and both tissue contraction and expression of TGF-β1 were determined for soft-tissue fibrosis 3 months after irradiation. In vitro, the effect of EsA on radiation-induced nitric oxide (NO) and cytokine production in different cell types was measured by application of 2, 4, and 8 Gy. Results: In vivo, EsA reduced levels of IL-1α, MCP-1, VEGF, and TGF-β1 in cutaneous tissue and reduced soft-tissue toxicity. In vitro, EsA inhibited the IL-1α ordinarily produced after 4 Gy in A431 cells. In Raw264.7 cells, EsA reduced levels of IL-1α, IL-1β, and NO production costimulated by radiation and lipopolysaccharide (LPS). In L-929 cells, EsA inhibited VEGF, TNF, and MCP-1 production at 2, 4, and 8 Gy. Conclusions: Esculentoside A protects soft tissues against radiation toxicity through inhibiting the production of several proinflammatory cytokines and inflammatory mediators in epithelial cells, macrophages, fibroblasts, and skin tissue

  11. Radiation induced diffusion as a method to protect surface

    International Nuclear Information System (INIS)

    Baumvol, I.J.R.

    1980-01-01

    Radiation induced diffusion forms a coating adeherent and without interface on the surface of metalic substrates. This coating improves the behaviour of metal to corrosion and abrasion. The effect of radiation induced diffusion of tin and calcium on pure iron surface is described and analyzed in this work. (author) [pt

  12. Allicin Protects against Lipopolysaccharide-Induced Acute Lung ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the ...

  13. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    The effects of NO on alleviating arsenic-induced oxidative damage in tall fescue leaves were investigated. Arsenic (25 M) treatment induced significantly accumulation of reactive oxygen species (ROS) and led to serious lipid peroxidation in tall fescue leaves and the application of 100 M SNP before arsenic stress resulted ...

  14. Homologous series of induced early mutants in indican rice. Pt.1. The production of homologous series of early mutants

    International Nuclear Information System (INIS)

    Chen Xiulan; Yang Hefeng; He Zhentian; Han Yuepeng; Liu Xueyu

    1999-01-01

    The percentage of homologous series of early mutants induced from the same Indican rice variety were almost the same (1.37%∼1.64%) in 1983∼1993, but the ones from the different eco-typical varieties were different. The early variety was 0.73%, the mid variety was 1.51%, and the late variety was 1.97%. The percentage of homologous series of early mutants from the varieties with the same pedigree and relationship were similar, but the one from the cog nation were lower than those from distant varieties. There are basic laws and characters in the homologous series of early mutants: 1. The inhibited phenotype is the basic of the homologous series of early mutants; 2. The production of the homologous series of early mutants is closely related with the growing period of the parent; 3. The parallel mutation of the stem and leaves are simultaneously happened with the variation of early or late maturing; 4. The occurrence of the homologous series of early mutants is in a state of imbalance. According to the law of parallel variability, the production of homologous series of early mutants can be predicted as long as the parents' classification of plant, pedigree and ecological type are identified. Therefore, the early breeding can be guided by the law of homologous series of early mutants

  15. Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer's Disease.

    Science.gov (United States)

    Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

    2018-01-01

    Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer's disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD.

  16. Protective Mechanisms of Nitrone Antioxidants in Kainic Acid Induced Neurodegeneration

    National Research Council Canada - National Science Library

    Bing, Guoying

    2001-01-01

    .... This model has been widely used as a model for studying human temporal lobe epilepsy. The delayed neuronal degeneration induced by kainic acid resembles CNS neuronal injury, repair, and plasticity...

  17. Protective Mechanisms of Nitrone Antioxidants in Kainic Acid Induced Neurodegeneration

    National Research Council Canada - National Science Library

    Bing, Guoying

    2000-01-01

    .... This model has been widely used as a model for studying human temporal lobe epilepsy. The delayed neuronal degeneration induced by kainic acid resembles CNS neuronal injury, repair, and plasticity...

  18. Protective antitumor activity induced by a fusion vaccine with murine ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... were analyzed. Inhibition of tumor-induced angiogenesis and prolonged survival were shown in mice ... (iDCs) through chemokine receptor CCR6 but also by up- ..... catenin proteins in metastatic prostate cancer cells in bone.

  19. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... 1Department of Soil and Water Science, College of Resources and Environment, ... alleviated arsenic-induced electrolyte leakage and malondiadehyde (MDA) content in ..... gene construct for environmental arsenic detection.

  20. Qidantongmai Protects Endothelial Cells Against Hypoxia-Induced ...

    African Journals Online (AJOL)

    induced damage. The ability of QDTM to modulate the serum VEGF-A level may play an important role in its effects on endothelial cells. Key words: Traditional Chinese Medicine, human umbilical vein endothelial cells, hypoxia, VEGF ...

  1. Radiation protection program for early detection of breast cancer in a mammography facility

    International Nuclear Information System (INIS)

    Mariana, Villagomez Casimiro; Cesar, Ruiz Trejo; Ruby, Espejo Fonseca

    2014-01-01

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1–4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)– presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied

  2. Early national and international recommendations for X-ray and radiation protection

    International Nuclear Information System (INIS)

    Tesinska, E.

    2008-01-01

    The first three decades of pioneering work in the field of X-ray and natural radioactivity research and use took its toll all over the world because of lack of knowledge and caution. Coordinated, international cooperation in the field of X-ray and radium protection and standardization of measures was established after the World War I. The First and the Second International Congress of Radiology held in London in 1925 and in Stockholm in 1928 respectively, played a crucial role in it. Based on these congresses' initiatives and resolutions, the International X-ray Unit Committee and the International X-ray and Radium Protection Committee were established in 1828. The early recommendations on the international X-ray unit and on X-ray and radium protection, as passed by the Second International Congress of Radiology in Stockholm in 1928, are presented and compared with two related national initiatives, namely with the Memorandum No. 1 (July 1921) of the British X-ray and Radium Protection Committee, and with a draft of a legal measure regarding the X-ray and radium treatment regulation in Czechoslovakia, which was put together by the Czechoslovak Society of Radiology and the Vereinigung der deutschen Roentgenologen und Radiologen in der Tschechoslowakischen Republik in 1927 at a request of the Chamber of Doctor of Medicine for Bohemia and Moravia and in response to the international initiatives in that field. (author)

  3. Radiation protection program for early detection of breast cancer in a mammography facility

    Energy Technology Data Exchange (ETDEWEB)

    Mariana, Villagomez Casimiro, E-mail: marjim10-66@ciencias.unam.mx, E-mail: cesar@fisica.unam.mx; Cesar, Ruiz Trejo, E-mail: marjim10-66@ciencias.unam.mx, E-mail: cesar@fisica.unam.mx [Instituto de Física, UNAM. Cd. Universitaria, CP 04510 (Mexico); Ruby, Espejo Fonseca [Instituto de Enfermedades de la Mama FUCAM-AC, CP 04980 (Mexico)

    2014-11-07

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1–4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)– presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.

  4. Radiation protection program for early detection of breast cancer in a mammography facility

    Science.gov (United States)

    Villagomez Casimiro, Mariana; Ruiz Trejo, Cesar; Espejo Fonseca, Ruby

    2014-11-01

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1-4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (radiation protection program in this work is applied.

  5. Protective Effect of Vitamin E on Nicotine Induced Reproductive ...

    African Journals Online (AJOL)

    The current study assessed the protective role of vitamin E in alleviating the detrimental effect of nicotine on reproductive functions in male rats. Twenty four male albino rats were divided into four groups of six rats. Control group was treated orally with 1.1 ml/kg body weight normal saline, nicotine treated group received 1.0 ...

  6. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chenglong [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zheng, Haining [Department of Hyperbaric Oxygen, Nanjing General Hospital of Nanjing Military Command, Nanjing (China); Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Ding, Dafa, E-mail: dingdafa2004@aliyun.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Lu, Yibing, E-mail: luyibing2004@126.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  7. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    International Nuclear Information System (INIS)

    Dong, Chenglong; Zheng, Haining; Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng; Ding, Dafa; Lu, Yibing

    2015-01-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK

  8. No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

    Directory of Open Access Journals (Sweden)

    Nilgün Gedik

    Full Text Available Remote ischemic preconditioning (RIPC by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG. Activation of signal transducer and activator of transcription 5 (STAT5 in left ventricular (LV myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation or placebo (cuff deflated before skin incision (n = 10/10. Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline and at early (5-10 min reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002. Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12 complex, light chain 3 (LC3, parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02. STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05.Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.

  9. Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang, E-mail: yangsun@nju.edu.cn; Wu, Xuefeng, E-mail: wuxf@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

    2016-07-15

    Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

  10. Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

    International Nuclear Information System (INIS)

    Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang; Wu, Xuefeng; Xu, Qiang

    2016-01-01

    Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

  11. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

    Directory of Open Access Journals (Sweden)

    Lauren G Holinka

    Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

  12. Remembrances of the early fifteen years of radiation protection at the National Atomic Energy Commission. Part 2

    International Nuclear Information System (INIS)

    Placer, Alejandro E.

    2005-01-01

    Personal memories on the origin of radiation protection activities in Argentina. This second part covers the period from 1957 to the early sixties and describes the persons and facts that led to the future development of radiation protection in the country [es

  13. The Relationship between Sun Protection Policy and Associated Practices in a National Sample of Early Childhood Services in Australia

    Science.gov (United States)

    Ettridge, Kerry A.; Bowden, Jacqueline A.; Rayner, Joanne M.; Wilson, Carlene J.

    2011-01-01

    Limiting exposure to sunlight during childhood can significantly reduce the risk of skin cancer. This was the first national study to assess the sun protection policies and practices of early childhood services across Australia. It also examined the key predictors of services' sun protection practices. In 2007, 1017 respondents completed a…

  14. Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease.

    Science.gov (United States)

    Richner, Justin M; Jagger, Brett W; Shan, Chao; Fontes, Camila R; Dowd, Kimberly A; Cao, Bin; Himansu, Sunny; Caine, Elizabeth A; Nunes, Bruno T D; Medeiros, Daniele B A; Muruato, Antonio E; Foreman, Bryant M; Luo, Huanle; Wang, Tian; Barrett, Alan D; Weaver, Scott C; Vasconcelos, Pedro F C; Rossi, Shannan L; Ciaramella, Giuseppe; Mysorekar, Indira U; Pierson, Theodore C; Shi, Pei-Yong; Diamond, Michael S

    2017-07-13

    The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Tomato consumption protected against gamma radiation–induced ...

    African Journals Online (AJOL)

    Microscopically, radiation induced histological alterations in the cerebellum, dentate gyrus and cornu ammonis 3. Co-treatment of radiation with TPP reduced the effect of radiation on the histological, haematological and, neurobehavioural alterations. In conclusion, Lycopersicon esculentum as tomato pomace powder ...

  16. Protection of Chinese herbs against Adenine-induced chronic renal ...

    African Journals Online (AJOL)

    The aim of the study is to evaluate the efficacy of Chinese herbs (Angelica sinensis, Ligusticum wallichii, Salvia miltiorrhiza, Rhizoma dioscoreae, Rhodiola crenilata, Astragalus membranaceus and Angelica sinensis) on adenine-induced chronic renal failure in rats. 30 age-matched male Wistar rats were divided into three ...

  17. Protective antitumor activity induced by a fusion vaccine with murine ...

    African Journals Online (AJOL)

    Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelialcadherin (VE-cad) regulated angiogenesis is a potential target for anti-angiogenesis. Here, we develop a fusion vaccine plasmid DNA pSec-MBD2-VE-cad from VE-cad and murine beta defensin2 (MBD2) to induce immunity for ...

  18. Baseline Survey of Sun-Protection Knowledge, Practices and Policy in Early Childhood Settings in Queensland, Australia

    Science.gov (United States)

    Harrison, Simone L.; Saunders, V.; Nowak, M.

    2007-01-01

    Excessive exposure to sunlight during early childhood increases the risk of developing skin cancer. Self-administered questionnaires exploring sun-protection knowledge, practices and policy were mailed to the directors/co-ordinators/senior teachers of all known early childhood services in Queensland, Australia, in 2002 (n = 1383; 56.5% response).…

  19. Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.

    Science.gov (United States)

    Hou, Yue; Xie, Guanbo; Liu, Xia; Li, Guoxun; Jia, Congcong; Xu, Jinghua; Wang, Bing

    2016-03-01

    The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown. This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice. Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines. Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group. Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

  20. Different immunization routes induce protection against Aeromonas salmonicida through different immune mechanisms in rainbow trout

    DEFF Research Database (Denmark)

    Villumsen, Kasper Rømer; Raida, Martin Kristian

    in fish immunology and vaccinology, resulting in the development of both oral, immersion and injectable vaccine strategies over time. Applying mineral oil adjuvants, injectable vaccines inducing high levels of protection in salmon (Salmo salar) rose to prominence in the 1990’s. In general injectable......, adjuvanted vaccines have been shown to induce long-lasting increases in specific antibody levels. In general the majority of the published work concerning vaccination against A. salmonicida has been conducted on salmon. Using injectable oil-adjuvanted vaccines, we have previously shown that the induced level...... against A. salmonicida. The effect of immersion vaccination against A. salmonicida has been questioned over time. While some have presented excellent protection as a result of immersion vaccines, others have reported limited or absent protective effects. We have performed experiments on the protection...

  1. Gram staining of protected pulmonary specimens in the early diagnosis of ventilator-associated pneumonia.

    Science.gov (United States)

    Mimoz, O; Karim, A; Mazoit, J X; Edouard, A; Leprince, S; Nordmann, P

    2000-11-01

    We evaluated prospectively the use of Gram staining of protected pulmonary specimens to allow the early diagnosis of ventilator-associated pneumonia (VAP), compared with the use of 60 bronchoscopic protected specimen brushes (PSB) and 126 blinded plugged telescopic catheters (PTC) obtained from 134 patients. Gram stains were from Cytospin slides; they were studied for the presence of microorganisms in 10 and 50 fields by two independent observers and classified according to their Gram stain morphology. Quantitative cultures were performed after serial dilution and plating on appropriate culture medium. A final diagnosis of VAP, based on a culture of > or = 10(3) c.f.u. ml-1, was established after 81 (44%) samplings. When 10 fields were analysed, a strong relationship was found between the presence of bacteria on Gram staining and the final diagnosis of VAP (for PSB and PTC respectively: sensitivity 74 and 81%, specificity 94 and 100%, positive predictive value 91 and 100%, negative predictive value 82 and 88%). The correlation was less when we compared the morphology of microorganisms observed on Gram staining with those of bacteria obtained from quantitative cultures (for PSB and PTC respectively: sensitivity 54 and 69%, specificity 86 and 89%, positive predictive value 72 and 78%, negative predictive value 74 and 84%). Increasing the number of fields read to 50 was associated with a slight decrease in specificity and positive predictive value of Gram staining, but with a small increase in its sensitivity and negative predictive value. The results obtained by the two observers were similar to each other for both numbers of fields analysed. Gram staining of protected pulmonary specimens performed on 10 fields predicted the presence of VAP and partially identified (using Gram stain morphology) the microorganisms growing at significant concentrations, and could help in the early choice of the treatment of VAP. Increasing the number of fields read or having the Gram

  2. The effect of short-term vitamin E against radioiodine-induced early lacrimal gland damage

    International Nuclear Information System (INIS)

    Acar, Ugur; Atilgan, Hasan Ikbal; Acar, Damla Erginturk; Yalniz-Akkaya, Zuleyha; Korkmaz, Meliha; Koca, Goekhan; Yumusak, Nihat

    2013-01-01

    Radioiodine (RAI) is a well-known radionuclide which is used in vivo both for diagnostic and therapeutic purposes, particularly for the treatment of hyperthyroidism and thyroid cancer. Vitamin E is a well-known antioxidant vitamin. The aim of this study was to evaluate whether there was a protective effect of short-term vitamin E on RAI-induced lacrimal gland early damage in experimental animal models. Twentyfour rats were randomly divided into two groups. The first group (RAI group) was administreted 3 mCi 131 I by gastric gavage and 1 mL physiological saline intraperitoneally. The second group (RAI+Vitamin E) was administrated 3 mCi 131 I by gastric gavage and 1 mL vitamin E intraperitoneally. After 24 h of the last dose being administered on the 7th day, the animals were decapitated. The lacrimal glands [Intraorbital (IG), extraorbital (EG) and harderian glands (HG)] of the rats were removed for histopathological examination. Periductal and/or periacinar fibrosis in all lacrimal glands were observed to be statistically significantly less frequent in the RAI + Vitamin E group compared to the RAI group. The existence of the abnormal lobular pattern and peripheral basophilia and irregular nucleus shape in IG and in EG, the poorly defined acidophilic cell outline and periductal infiltration in IG and in HG were observed to be statistically significantly less frequent in the RAI + Vitamin E group than in the RAI group. According to study results, histopathological examinations revealed that vitamin E protects rat lacrimal glands against RAI-related early damage. (author)

  3. Anti-apoptotic peptides protect against radiation-induced cell death

    International Nuclear Information System (INIS)

    McConnell, Kevin W.; Muenzer, Jared T.; Chang, Kathy C.; Davis, Chris G.; McDunn, Jonathan E.; Coopersmith, Craig M.; Hilliard, Carolyn A.; Hotchkiss, Richard S.; Grigsby, Perry W.; Hunt, Clayton R.

    2007-01-01

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues

  4. Abscisic acid protects bean leaves from ozone-induced phytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, R.A.; Adedipe, N.O.; Ormrod, D.P.

    1972-01-01

    Abscisic acid treatment of primary bean leaves caused a partial closure of stomates and thus considerably reduced the phytotoxicity of ozone. The symptoms of ozone-induced phytotoxicity in the water-treated leaves are a marked decrease in chlorophyll and slight decreases in the levels of protein and RNA. The evidence indicates that ozone injury to leaves is not metabolically related to normal leaf senescence.

  5. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  6. Protective Role of Aldose Reductase Deletion in an Animal Model of Oxygen-Induced Retinopathy

    Directory of Open Access Journals (Sweden)

    Zhongjie Fu

    2011-05-01

    Full Text Available Retinopathy of prematurity (ROP is a common disease occurred in premature babies. Both vascular abnormality and neural dysfunction of the retina were reported, and oxidative stress was involved. Previously, it has been showed that deficiency of aldose reductase (AR, the rate-limiting enzyme in polyol pathway, lowered oxidative stress. Here, the effect of AR deletion on neonatal retinal injury was investigated by using a mouse model of ROP (oxygen-induced retinopathy, OIR. Seven-day-old pups were exposed to 75% oxygen for 5 days and then returned to room air. The vascular changes and neuronal/glial responses were examined and compared between wild-type and AR-deficient OIR mice. Significantly reduced vaso-obliterated area, blood vessel leakage, and early revascularization were observed in AR-deficient OIR mice. Moreover, reduced amacrine cells and less distorted strata were observed in AR-deficient OIR mice. Less astrocytic immunoreactivity and reduced Müller cell gliosis were also observed in AR-deficient mice. After OIR, nitrotyrosine immunoreactivity and poly (ADP-ribose (PAR translocation, which are two oxidative stress markers, were decreased in AR-deficient mice. Significant decrease in VEGF, pho-Erk1/2, pho-Akt, and pho-I?B expression was found in AR-deficient OIR retinae. Thus, these observations suggest that the deficiency of aldose reductase may protect the retina in the OIR model.

  7. Biomarkers for the early detection of cancer treatment induced cardiotoxicity

    NARCIS (Netherlands)

    Bulten, Ben

    2016-01-01

    In this thesis, the role of several imaging and nonimaging markers for the detection of anthracycline-induced and trastuzumab-induced cardiotoxicity (respectively AIC and TIC) is evaluated. Especially, the pathophysiology of these processes and the interrelationship of the various markers are

  8. Failure of catalase to protect against aflatoxin B1-induced mouse lung tumorigenicity

    International Nuclear Information System (INIS)

    Guindon, Katherine A.; Foley, Julie F.; Maronpot, Robert R.; Massey, Thomas E.

    2008-01-01

    The carcinogenic mycotoxin aflatoxin B 1 (AFB 1 ) induces 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in mouse lung, an effect that can be prevented by treatment with polyethylene glycol-conjugated catalase (PEG-CAT). G → T transversion mutation in K-ras, an early event in AFB 1 -induced mouse lung carcinogenesis, is thought to result from AFB 1 -8,9-exo-epoxide binding to DNA to form AFB 1 -N 7 -guanine, but may also result from formation of 8-OHdG. Therefore, oxidative DNA damage may be important in AFB 1 carcinogenicity. The objective of this study was to determine whether PEG-CAT would prevent AFB 1 tumorigenicity. Mouse lung tumorigenesis was assessed following treatment of female A/J mice with 300 kU/kg PEG-CAT ip and/or 50 mg/kg AFB 1 . Mice were killed 7 months post-treatment and tumors greater than 1 mm in diameter were excised. Unexpectedly, the mean number of tumors per mouse in the PEG-CAT + AFB 1 group (8.81 ± 3.64, n = 47) was greater than that of the group treated with AFB 1 alone (7.05 ± 3.45, n = 42) (P 1 were larger than those from mice treated with AFB 1 alone (P 1 and PEG-CAT + AFB 1 groups (P > 0.05). In vitro incubation with mouse liver catalase (CAT) resulted in conversion of [ 3 H]AFB 1 into a DNA-binding species, a possible explanation for the results observed in vivo. These results demonstrate that PEG-CAT is not protective against AFB 1 carcinogenicity in mouse lung despite preventing DNA oxidation

  9. Antithrombin III Protects Against Contrast-Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Zeyuan Lu

    2017-03-01

    Full Text Available We previously reported that insufficiency of antithrombin III (ATIII, the major anti-coagulation molecule in vivo, exacerbated renal ischemia-reperfusion injury in animal models and possibly humans. In the present study, we investigated the relationship between ATIII level and contrast induced nephropathy (CIN in patients and examined therapeutic effect of ATIII on CIN in Sprague-Dawley rats. Patients with low ATIII activity presented a higher incidence of acute kidney injury (AKI following coronary angiography. ATIII (500 μg/kg was intravenously injected before or after the induction of AKI in rats. Our data demonstrated ATIII significantly attenuated the elevation of serum creatinine, blood urea nitrogen, and renal histological injury. The beneficial effects of ATIII were accompanied by diminished renal inflammatory response, oxidative stress, cell apoptosis and improved renal blood flow in rats. In conclusion, ATIII appears to attenuate CIN through inhibiting inflammation, oxidative stress, apoptosis and improving renal blood flow. ATIII administration may represent a promising strategy for the prevention and treatment of contrast-induced AKI.

  10. Sestrin2 protects the myocardium against radiation-induced damage

    International Nuclear Information System (INIS)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong; Zeng, Jing; Wang, Hong-Mei

    2016-01-01

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  11. Anesthetic-Induced Oxidative Stress and Potential Protection

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    2010-01-01

    Full Text Available Prolonged exposure of developing mammals to general anesthetics affects the N-methyl-D-aspartate (NMDA–type glutamate or γ-aminobutyric acid (GABA receptor systems and enhances neuronal toxicity. Stimulation of immature neurons by NMDA antagonists or GABA agonists is thought to increase overall nervous system excitability and may contribute to abnormal neuronal cell death during development. Although the precise mechanisms by which NMDA antagonists or GABA agonists cause neuronal cell death are still not completely understood, up-regulation of the NMDA receptor subunit NR1 may be an initiative factor in neuronal cell death. It is increasingly apparent that mitochondria lie at the center of the cell death regulation process. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers. Prevention of neuronal death by catalase and superoxide dismutase in vitro, or by M40403 (superoxide dismutase mimetic in vivo, supports the contention that the involvement of reactive oxygen species (ROS and the nature of neuronal cell death in rodents is mainly apoptotic. However, more evidence is necessary to in order verify the role of the NMDA receptor subunit NR1 and ROS in anesthetic-induced neurodegeneration.

  12. Sestrin2 protects the myocardium against radiation-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong [Shengjing Hospital of China Medical University, Department of Medical Oncology, Cancer Center, Shenyang (China); Zeng, Jing [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Wang, Hong-Mei [Nanfang Hospital of Southern Medical University, Department of Radiation Oncology, Guangzhou (China)

    2016-05-15

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  13. Chromium-induced membrane damage: protective role of ascorbic acid.

    Science.gov (United States)

    Dey, S K; Nayak, P; Roy, S

    2001-07-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). It has been observed that the intoxication with chromium (i.p.) at the dose of 0.8 mg/100 g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospholipid of both liver and kidney. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities were significantly decreased in both liver and kidney after chromium treatment, except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid (i.p. at the dose of 0.5 mg/100 g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  14. Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

    Science.gov (United States)

    Dettmar, Anne K.; Binder, Elisabeth; Greiner, Friederike R.; Liebau, Max C.; Kurschat, Christine E.; Jungraithmayr, Therese C.; Saleem, Moin A.; Schmitt, Claus-Peter; Feifel, Elisabeth; Orth-Höller, Dorothea; Kemper, Markus J.; Pepys, Mark; Würzner, Reinhard

    2014-01-01

    Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option. PMID:24566618

  15. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis.

    Science.gov (United States)

    Shaw, Catherine A; Webb, David J; Rossi, Adriano G; Megson, Ian L

    2009-05-07

    Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMvarphi), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR) spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMvarphi. Resultant MDMvarphi were treated for 24 h with DETA/NO (100 - 1000 muM) or GEA-3162 (10 - 300 muM) in the presence or absence of BAY 41-2272 (1 muM), isobutylmethylxanthine (IBMX; 1 muM), 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 muM) or 8-bromo-cGMP (1 mM). Apoptosis in MDMvarphi was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO) had no effect on cell viability, but ONOO- (GEA-3162) caused a concentration-dependent induction of apoptosis in MDMvarphi. Preconditioning of MDMvarphi with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX), or the NO-independent stimulator of soluble guanylate cyclase, BAY 41-2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner. These results

  16. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  17. Genetic Test Reporting and Counseling for Melanoma Risk in Minors May Improve Sun Protection Without Inducing Distress.

    Science.gov (United States)

    Stump, Tammy K; Aspinwall, Lisa G; Kohlmann, Wendy; Champine, Marjan; Hauglid, Jamie; Wu, Yelena P; Scott, Emily; Cassidy, Pamela; Leachman, Sancy A

    2018-01-19

    Genetic testing of minors is advised only for conditions in which benefits of early intervention outweigh potential psychological harms. This study investigated whether genetic counseling and test reporting for the CDKN2A/p16 mutation, which confers highly elevated melanoma risk, improved sun protection without inducing distress. Eighteen minors (M age  = 12.4, SD = 1.9) from melanoma-prone families completed measures of protective behavior and distress at baseline, 1 week (distress only), 1 month, and 1 year following test disclosure. Participants and their mothers were individually interviewed on the psychological and behavioral impact of genetic testing 1 month and 1 year post-disclosure. Carriers (n = 9) and noncarriers (n = 9) reported significantly fewer sunburns and a greater proportion reported sun protection adherence between baseline and 1 year post-disclosure; results did not vary by mutation status. Anxiety symptoms remained low post-disclosure, while depressive symptoms and cancer worry decreased. Child and parent interviews corroborated these findings. Mothers indicated that genetic testing was beneficial (100%) because it promoted risk awareness (90.9%) and sun protection (81.8%) without making their children scared (89.9%); several noted their child's greater independent practice of sun protection (45.4%). In this small initial study, minors undergoing CDKN2A/p16 genetic testing reported behavioral improvements and consistently low distress, suggesting such testing may be safely implemented early in life, allowing greater opportunity for risk-reducing lifestyle changes.

  18. Protective effects ofginger (Zingiberofficinale rhizomeextractonheat-induced testiculardamagein the mouse

    Directory of Open Access Journals (Sweden)

    bahram amuoghlitabrizi

    2013-11-01

    Full Text Available Infertility is a complicated problem with medical significance. Gingeras amedicinalherb is used to treata number of diseasessuch assexualweakness. The aim of this study was to evaluate the effects of ginger rhizome extract on heat-induced testicular damage in the mouse. Fourtymale mice were randomly divided into 4 equal groups including: 1- Control, 2- heat stressed, 3 and 4- stressed and treated with ginger extract (1/5 and 3 mg/animal/day. The scrotum of experimental mice was immersed for 20 min in a water bath at 42°C. Control mice were similarly treated except that the water bath was maintained at 23°C. Mice were euthanized after 50 days. Blood samples were collected for analysis of testosterone levels. Testes were removed for histopathological assessment and oxidant/antioxidant status. Heat stress significantly reduced blood testosterone level and increased lipid peroxidation product and decreased antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase (p

  19. Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish.

    Science.gov (United States)

    Félix, Luís M; Serafim, Cindy; Valentim, Ana M; Antunes, Luís M; Matos, Manuela; Coimbra, Ana M

    2017-09-05

    Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1-4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1-4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Radiation induced cancer risk, detriment and radiation protection

    International Nuclear Information System (INIS)

    Sinclair, W.K.

    1992-01-01

    Recommendations on radiation protection limits for workers and for the public depend mainly on the total health detriment estimated to be the result of low dose ionizing radiation exposure. This detriment includes the probability of a fatal cancer, an allowance for the morbidity due to non-fatal cancer and the probability of severe hereditary effects in succeeding generations. In a population of all ages, special effects on the fetus particularly the risk of mental retardation at defined gestational ages, should also be included. Among these components of detriment after low doses, the risk of fatal cancer is the largest and most important. The estimates of fatal cancer risk used by ICRP in the 1990 recommendations were derived almost exclusively from the study of the Japanese survivors of the atomic bombs of 1945. How good are these estimates? Uncertainties associated with them, apart from those due to limitations in epidemiological observation and dosimetry, are principally those due to projection forward in time and extrapolation from high dose and dose rate to low dose and dose rate, each of which could after the estimate by a factor of 2 or so. Recent estimates of risk of cancer derived directly from low dose studies are specific only within very broad ranges of risk. Nevertheless, such studies are important as confirmation or otherwise of the estimates derived from the atomic bomb survivors. Recent U.S. British and Russian studies are examined in this light. (author)

  1. Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis.

    Science.gov (United States)

    Xu, Qingfu; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina; Pichichero, Michael E

    2015-02-18

    Due to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. C57BL/6J infant mice were intramuscularly vaccinated at age 1-3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. PPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. Trivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation

  2. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    Science.gov (United States)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  3. Application of Advanced Wide Area Early Warning Systems with Adaptive Protection

    Energy Technology Data Exchange (ETDEWEB)

    Blumstein, Carl [Univ. of California, Berkeley, CA (United States); Cibulka, Lloyd [Univ. of California, Berkeley, CA (United States); Thorp, James [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Centeno, Virgilio [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); King, Roger [Mississippi State Univ., Mississippi State, MS (United States); Reeves, Kari [Mississippi State Univ., Mississippi State, MS (United States); Ashrafi, Frank [Southern California Edison Co., Rosemead, CA (United States); Madani, Vahid [Pacific Gas & Electric Co., San Francisco, CA (United States)

    2014-09-30

    Recent blackouts of power systems in North America and throughout the world have shown how critical a reliable power system is to modern societies, and the enormous economic and societal damage a blackout can cause. It has been noted that unanticipated operation of protection systems can contribute to cascading phenomena and, ultimately, blackouts. This project developed and field-tested two methods of Adaptive Protection systems utilizing synchrophasor data. One method detects conditions of system stress that can lead to unintended relay operation, and initiates a supervisory signal to modify relay response in real time to avoid false trips. The second method detects the possibility of false trips of impedance relays as stable system swings “encroach” on the relays’ impedance zones, and produces an early warning so that relay engineers can re-evaluate relay settings. In addition, real-time synchrophasor data produced by this project was used to develop advanced visualization techniques for display of synchrophasor data to utility operators and engineers.

  4. Bifidobacterium animalis AHC7 protects against pathogen-induced NF-kappaB activation in vivo

    LENUS (Irish Health Repository)

    O'Mahony, David

    2010-12-22

    Abstract Background Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. Results Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3\\/CD28 stimulated Peyer\\'s patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. Conclusion Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism

  5. Protective effect of chlorpromazine on TNF-mediated hapten-induced irritant reaction.

    Science.gov (United States)

    Erroi, A; Fantuzzi, G; Demitri, M T; Echtenacher, B; Gnocchi, P; Isetta, A; Ghezzi, P

    1995-01-01

    Picryl chloride-induced irritant reaction (IR) was shown to be mediated by tumor necrosis factor (TNF). Anti-TNF monoclonal antibodies, but not interleukin 1 receptor antagonist (IL-1 Ra), had a protective effect. Chlorpromazine (CPZ), an inhibitor of TNF synthesis, protected against IR and inhibited the IR-associated TNF induction in ear homogenates. Investigation of the role of polymorphonuclear leukocyte (PMN) in neutropenic mice showed that neutropenia did not prevent the development of the IR.

  6. EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

    OpenAIRE

    Chen, Dan; Kanthasamy, Anumantha G.; Reddy, Manju B.

    2015-01-01

    Background. Parkinson's disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (?)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulato...

  7. Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

    Science.gov (United States)

    2010-04-09

    Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol...provided the original work is properly cited. ResearchDecay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury...deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured

  8. Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

    Science.gov (United States)

    Kast, Brigitte; Schori, Christian; Grimm, Christian

    2016-05-01

    Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    OpenAIRE

    Aicha Fassi Fihri; Noori S. Al-Waili; Redouan El-Haskoury; Meryem Bakour; Afaf Amarti; Mohammad J. Ansari; Badiaa Lyoussi

    2016-01-01

    Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: tr...

  10. Portulaca oleracea extracts protect human keratinocytes and fibroblasts from UV-induced apoptosis.

    Science.gov (United States)

    Lee, Suyeon; Kim, Ki Ho; Park, Changhoon; Lee, Jong-Suk; Kim, Young Heui

    2014-10-01

    Portulaca oleracea extracts, known as Ma Chi Hyun in the traditional Korean medicine, show a variety of biomedical efficacies including those in anti-inflammation and anti-allergy. In this study, we investigate the protective activity of the P. oleracea extracts against UVB-induced damage in human epithelial keratinocytes and fibroblasts by several apoptosis-related tests. The results suggest that P. oleracea extracts have protective effects from UVB-induced apoptosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Regulation of radiation protective agents on cell damage induced by reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hee; Lee, Si Eun; Ju, Eun Mi; Gao, Eu Feng [Kyung Hee University, Seoul (Korea)

    2002-04-01

    In this study, we developed candidates of new radio-protective agents and elucidated the regulation mechanism of these candidates on cell damage induced by reactive oxygen species. The methanol extracts and ethylacetate fractions of NP-1, NP-5, NP-7, NP-11, NP-12 and NP-14 showed higher radical scavenging activity. The extracts of NP-7, NP-12 and NP-14 showed strong protective effect against oxidative damage induced by UV and H{sub 2}O{sub 2}. The most of samples enhanced SOD, CAT and GPX activity in V79-4 cells. The protective effect of samples on H{sub 2}O{sub 2}-induced apoptosis was observed with microscope and flow cytometer. Cells exposed to H{sub 2}O{sub 2} exhibit distinct morphological features of programmed cell death, such as nuclear fragmentation and increase in the percentage of cells with a sub-G1 DNA content. However, cells which was pretreated with samples significantly reduced the characteristics of apoptotic cells. Their morphological observation and DNA profiles were similar to those of the control cells. NP-14 which had excellent antioxidant activity restored G2/M arrest induced by oxidative stress. These data suggested that natural medicinal plants protected H{sub 2}O{sub 2}-induced apoptosis. 42 refs., 29 figs., 11 tabs. (Author)

  12. Melatonin protects bone marrow mesenchymal stem cells against iron overload-induced aberrant differentiation and senescence.

    Science.gov (United States)

    Yang, Fan; Yang, Lei; Li, Yuan; Yan, Gege; Feng, Chao; Liu, Tianyi; Gong, Rui; Yuan, Ye; Wang, Ning; Idiiatullina, Elina; Bikkuzin, Timur; Pavlov, Valentin; Li, Yang; Dong, Chaorun; Wang, Dawei; Cao, Yang; Han, Zhenbo; Zhang, Lai; Huang, Qi; Ding, Fengzhi; Bi, Zhengang; Cai, Benzhi

    2017-10-01

    Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Pre-Treatment with Amifostine Protects against Cyclophosphamide-Induced Disruption of Taste in Mice

    Science.gov (United States)

    Mukherjee, Nabanita; Carroll, Brittany L.; Spees, Jeffrey L.; Delay, Eugene R.

    2013-01-01

    Cyclophosphamide (CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect against chemotherapy-induced damage to taste buds using a mouse model of CYP injury. We conducted detection threshold tests to measure changes in sucrose taste sensitivity and found that administration of amifostine 30 mins prior to CYP injection protected against CYP-induced loss in taste sensitivity. Morphological studies showed that pre-treatment with amifostine prevented CYP-induced reduction in the number of fungiform taste papillae and increased the number of taste buds. Immunohistochemical assays for markers of the cell cycle showed that amifostine administration prevented CYP-induced inhibition of cell proliferation and also protected against loss of mature taste cells after CYP exposure. Our results indicate that treatment of cancer patients with amifostine prior to chemotherapy may improve their sensitivity for taste stimuli and protect the taste system from the detrimental effects of chemotherapy. PMID:23626702

  14. Pre-treatment with amifostine protects against cyclophosphamide-induced disruption of taste in mice.

    Directory of Open Access Journals (Sweden)

    Nabanita Mukherjee

    Full Text Available Cyclophosphamide (CYP, a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect against chemotherapy-induced damage to taste buds using a mouse model of CYP injury. We conducted detection threshold tests to measure changes in sucrose taste sensitivity and found that administration of amifostine 30 mins prior to CYP injection protected against CYP-induced loss in taste sensitivity. Morphological studies showed that pre-treatment with amifostine prevented CYP-induced reduction in the number of fungiform taste papillae and increased the number of taste buds. Immunohistochemical assays for markers of the cell cycle showed that amifostine administration prevented CYP-induced inhibition of cell proliferation and also protected against loss of mature taste cells after CYP exposure. Our results indicate that treatment of cancer patients with amifostine prior to chemotherapy may improve their sensitivity for taste stimuli and protect the taste system from the detrimental effects of chemotherapy.

  15. Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

    Energy Technology Data Exchange (ETDEWEB)

    Jonasson, Sofia, E-mail: sofia.jonasson@foi.se [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Wigenstam, Elisabeth [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden); Koch, Bo [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Bucht, Anders [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden)

    2013-09-01

    Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as AHR in

  16. Rosiglitazone protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity

    International Nuclear Information System (INIS)

    Jung, Tae Woo; Lee, Ji Young; Shim, Wan Sub; Kang, Eun Seok; Kim, Soo Kyung; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo

    2006-01-01

    Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of the intracellular reactive oxygen species level and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In this study, we investigated the protective effects of rosiglitazone on acetaldehyde-induced apoptosis in human neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde-induced apoptosis was moderately reversed by rosiglitazone treatment. Our results suggest that the protective effects of rosiglitazone on acetaldehyde-induced apoptosis may be ascribed to ability to induce the expression of anti-oxidant enzymes and to regulate Bcl-2 and Bax expression. These data indicate that rosiglitazone may provide a useful therapeutic strategy for the prevention of progressive neurodegenerative disease such as Parkinson's disease

  17. Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia.

    Science.gov (United States)

    Gorgias, N; Maidatsi, P; Tsolaki, M; Alvanou, A; Kiriazis, G; Kaidoglou, K; Giala, M

    1996-04-01

    The present study investigates whether under conditions of successive hypoxic exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia, protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia. The ultrastructural findings were also correlated with regional superoxide dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced ultrastructural changes consistent with the aspects of delayed neuronal death (DND). However, in preexposed animals hippocampal damage was attenuated in an inversely proportional way with the severity of the hypoxic pretreatment. The ultrastructural hypoxic tolerance findings were also closely related to increased regional SOD activity levels. Thus the activation of the endogenous antioxidant defense by hypoxic preconditioning, protects against hippocampal damage induced by severe hypoxia. The eventual contribution of increased endogenous adenosine and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

  18. Inflammatory cytokines protect retinal pigment epithelial cells from oxidative stress-induced death

    DEFF Research Database (Denmark)

    Juel, Helene B; Faber, Carsten; Svendsen, Signe Goul

    2013-01-01

    -mediated induction of the anti-oxidative stress response, upregulating protective anti-oxidant pathway(s). These findings suggest caution for the clinical use of anti-inflammatory agents in the management of immune-associated eye diseases such as age-related macular degeneration....... protected from cell death by the addition of PCM. This protection was conferred, at least in part, by IFNγ and TNFα. Cell death induced by H2O2 or NaIO3 was preceded by mitochondrial dysfunction and by p62 upregulation, both of which were attenuated by PCM and/or by IFNγ+TNFα. RPE cells co...

  19. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Pär I

    2012-01-01

    There is emerging evidence that early trauma-induced coagulopathy (TIC) is mechanistically linked to disruption of the vascular endothelium and its glycocalyx, assessed by thrombomodulin and syndecan 1, respectively. This study evaluated if degradation of the endothelial glycocalyx and ensuing...... release of its heparin-like substances induce autoheparinization and thereby contributes to TIC....

  20. Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available The potential cytotoxicity of cadmium selenide (CdSe quantum dots (QDs presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC50 = 20.4 μM. Pre-treatment with SFN (5 μM increased cell viability in response to CdSe QDs (20 μM from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3-6 h, followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy.

  1. Exercise Does Not Protect against MPTP-Induced Neurotoxicity in BDNF Happloinsufficent Mice

    OpenAIRE

    Gerecke, Kim M.; Jiao, Yun; Pagala, Viswajeeth; Smeyne, Richard J.

    2012-01-01

    Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN) dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF), have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is depende...

  2. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Tong, Liping; Yu, K.N.; Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi; Han, Wei

    2014-01-01

    Highlights: • We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. • Carbon monoxide inhibited proliferation via modulating the transforming growth factor β1 (TGF-β1)/nitric oxide (NO) signaling pathway. • Exogenous carbon monoxide has potential application in clinical radiotherapy. - Abstract: Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy

  3. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Liping [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Han, Wei, E-mail: hanw@hfcas.cn [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China)

    2014-01-15

    Highlights: • We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. • Carbon monoxide inhibited proliferation via modulating the transforming growth factor β1 (TGF-β1)/nitric oxide (NO) signaling pathway. • Exogenous carbon monoxide has potential application in clinical radiotherapy. - Abstract: Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy.

  4. RODOS and decision conferencing on early phase protective actions in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Haemaelaeinen, R.P.; Lindstedt, M. [Helsinki Univ. of Technology, Espoo (Finland). Systems Analysis Lab.; Sinkko, K.; Ammann, M. [Radiation and Nuclear Safety Authority, Helsinki (Finland); Salo, A

    1998-12-01

    This work was undertaken in order to study the utilisation of decision conferencing and of the RODOS system when considering early phase protective actions in the case of a nuclear accident. Altogether four meetings with various people were organised. The meetings were attended by competent national safety authorities and technical level decision-makers, i.e., those who are responsible for preparing advice or making presentations of matters for decision-makers responsible for practical implementation of actions. In the first set of meetings the aim was to elicit the factors/attributes that have to be considered when making a decision on sheltering, evacuation and iodine tablets. No uncertainties nor a threat phase were considered but everything was assumed to happen as described in the given scenario. The theme in the second set of meetings was to study the implications of probabilities. All information was calculated with the support of the RODOS system. In the early phases of a nuclear accident time is limited. Prestructured generic value trees or a list of possible attributes can help to save time. A possible approach is to present a large generic value tree. Either the decision-makers select the attributes that are suitable for the case in hand or the facilitator offers a choice between more structured value trees. The decision-makers then just examine the suggested value trees, check the generic tree to make sure that no important factors have been omitted and choose the appropriate one. As in previous RODOS exercises, the participants felt that RODOS could be used for providing information but found it more problematic to use decision analysis methods when deciding on countermeasures in the early phase of a nuclear accident. Furthermore, it was noted that understanding the actual meaning of `soft` attributes, such as socio-psychological impacts or political cost, was not a straightforward issue. Consequently, the definition of attributes in advance would be

  5. RODOS and decision conferencing on early phase protective actions in Finland

    International Nuclear Information System (INIS)

    Haemaelaeinen, R.P.; Lindstedt, M.; Salo, A.

    1998-12-01

    This work was undertaken in order to study the utilisation of decision conferencing and of the RODOS system when considering early phase protective actions in the case of a nuclear accident. Altogether four meetings with various people were organised. The meetings were attended by competent national safety authorities and technical level decision-makers, i.e., those who are responsible for preparing advice or making presentations of matters for decision-makers responsible for practical implementation of actions. In the first set of meetings the aim was to elicit the factors/attributes that have to be considered when making a decision on sheltering, evacuation and iodine tablets. No uncertainties nor a threat phase were considered but everything was assumed to happen as described in the given scenario. The theme in the second set of meetings was to study the implications of probabilities. All information was calculated with the support of the RODOS system. In the early phases of a nuclear accident time is limited. Prestructured generic value trees or a list of possible attributes can help to save time. A possible approach is to present a large generic value tree. Either the decision-makers select the attributes that are suitable for the case in hand or the facilitator offers a choice between more structured value trees. The decision-makers then just examine the suggested value trees, check the generic tree to make sure that no important factors have been omitted and choose the appropriate one. As in previous RODOS exercises, the participants felt that RODOS could be used for providing information but found it more problematic to use decision analysis methods when deciding on countermeasures in the early phase of a nuclear accident. Furthermore, it was noted that understanding the actual meaning of 'soft' attributes, such as socio-psychological impacts or political cost, was not a straightforward issue. Consequently, the definition of attributes in advance would be

  6. Protection against methamphetamine-induced neurotoxicity to neostriatal dopaminergic neurons by adenosine receptor activation.

    Science.gov (United States)

    Delle Donne, K T; Sonsalla, P K

    1994-12-01

    Methamphetamine (METH)-induced neurotoxicity to nigrostriatal dopaminergic neurons in experimental animals appears to have a glutamatergic component because blockade of N-methyl-D-aspartate receptors prevents the neuropathologic consequences. Because adenosine affords neuroprotection against various forms of glutamate-mediated neuronal damage, the present studies were performed to investigate whether adenosine plays a protective role in METH-induced toxicity. METH-induced decrements in neostriatal dopamine content and tyrosine hydroxylase activity in mice were potentiated by concurrent treatment with caffeine, a nonselective adenosine antagonist that blocks both A1 and A2 adenosine receptors. In contrast, chronic treatment of mice with caffeine through their drinking water for 4 weeks, which increased the number of adenosine A1 receptors in the neostriatum and frontal cortex, followed by drug washout, prevented the neurochemical changes produced by the treatment of mice with METH treatment. In contrast, this treatment did not prevent 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced dopaminergic neurotoxicity. Furthermore, concurrent administration of cyclopentyladenosine, an adenosine A1 receptor agonist, attenuated the METH-induced neurochemical changes. This protection by cyclopentyladenosine was blocked by cyclopentyltheophylline, an A1 receptor antagonist. These results indicate that activation of A1 receptors can protect against METH-induced neurotoxicity in mice.

  7. Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.

    Science.gov (United States)

    Albers, D S; Sonsalla, P K

    1995-12-01

    Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate

  8. Dendrobium nobile Lindl alkaloid, a novel autophagy inducer, protects against axonal degeneration induced by Aβ25-35 in hippocampus neurons in vitro.

    Science.gov (United States)

    Li, Li-Sheng; Lu, Yan-Liu; Nie, Jing; Xu, Yun-Yan; Zhang, Wei; Yang, Wen-Jin; Gong, Qi-Hai; Lu, Yuan-Fu; Lu, Yang; Shi, Jing-Shan

    2017-04-01

    Axonal degeneration is a pathological symbol in the early stage of Alzheimer's disease (AD), which can be triggered by amyloid-β (Aβ) peptide deposition. Growing evidence indicates that deficit of autophagy eventually leads to the axonal degeneration. Our previous studies have shown that Dendrobium nobile Lindl alkaloid (DNLA) had protective effect on neuron impairment in vivo and in vitro; however, the underlying mechanisms is still unclear. We exposed cultured hippocampus neurons to Aβ 25-35 to investigate the effect of DNLA in vitro. Axonal degeneration was evaluated by immunofluorescence staining and MTT assay. Neurons overexpressing GFP-LC3B were used to measure the formation of autophagosome. Autophagosome-lysosome fusion, the lysosomal pH, and cathepsin activity were assessed to reflect autophagy process. Proteins of interest were analyzed by Western blot. DNLA pretreatment significantly inhibited axonal degeneration induced by Aβ 25-35 peptide in vitro. Further studies revealed DNLA treatment increased autophagic flux through promoting formation and degradation of autophagosome in hippocampus neurons. Moreover, enhancement of autophagic flux was responsible for the protective effects of DNLA on axonal degeneration. DNLA prevents Aβ 25-35 -induced axonal degeneration via activation of autophagy process and could be a novel therapeutic target. © 2017 John Wiley & Sons Ltd.

  9. EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

    Directory of Open Access Journals (Sweden)

    Dan Chen

    2015-01-01

    Full Text Available Background. Parkinson’s disease (PD is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−-epigallocatechin-3-gallate (EGCG against 6-hydroxydopamine- (6-OHDA- induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05 increased divalent metal transporter-1 (DMT1 and hepcidin and decreased ferroportin 1 (Fpn1 level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, p<0.01 cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05, supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001 TH+ cell count (~3-fold and neurite length (~12-fold compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.

  10. Salivary a-amylase protects enamel surface against acid induced softening

    DEFF Research Database (Denmark)

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend

    Objectives: Recently we have demonstrated individual differences in protection against acid-induced enamel softening offered by experimentally developed saliva pellicles. Although ethnicity seemed to be related to protection level, the saliva proteins responsible for the differences were not iden......Objectives: Recently we have demonstrated individual differences in protection against acid-induced enamel softening offered by experimentally developed saliva pellicles. Although ethnicity seemed to be related to protection level, the saliva proteins responsible for the differences were......, and one Chinese. After collection, saliva was dialysed and lyophilised and re-dissolved at 0.5% in Type I water. Next, four polished bovine enamel specimens were immersed into each sample under gentle and constant shaking for 12 hours. Last, specimens were exposed to an erosive challenge of pH 2.3 for 4......-TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had...

  11. Recombinant Forms of Leishmania amazonensis Excreted/Secreted Promastigote Surface Antigen (PSA Induce Protective Immune Responses in Dogs.

    Directory of Open Access Journals (Sweden)

    Elodie Petitdidier

    2016-05-01

    Full Text Available Preventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA, from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombinant ES LaPSA-38S (rPSA or its carboxy terminal part LaPSA-12S (Cter-rPSA, combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21- and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recombinant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates.

  12. Bio-based resistance inducers for sustainable plant protection against pathogens

    Czech Academy of Sciences Publication Activity Database

    Burketová, Lenka; Trdá, Lucie; Ott, P.G.; Valentová, O.

    2015-01-01

    Roč. 33, č. 6 (2015), s. 994-1004 ISSN 0734-9750 R&D Projects: GA MŠk(CZ) LD14056 Institutional support: RVO:61389030 Keywords : Induced resistance * Elicitor * Chitosan Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 9.848, year: 2015

  13. New, coupling loss induced, quench protection system for superconducting accelerator magnets

    NARCIS (Netherlands)

    Ravaioli, Emanuele; Datskov, V.I.; Giloux, C.; Kirby, G.; ten Kate, Herman H.J.; Verweij, A.P.

    2014-01-01

    A new and promising method for the protection of superconducting high-field magnets is developed and tested on the so-called MQXC quadrupole magnet in the CERN magnet test facility. The method relies on a capacitive discharge system inducing during a few periods an oscillation of the transport

  14. Protective effect of Iris germanica L. in β-amyloid-induced animal ...

    African Journals Online (AJOL)

    Protective effect of Iris germanica L. in β-amyloid-induced animal model of alzheimer's disease. ... The day after surgery, animals in treatment groups received different doses of the aqueous extract of Iris by gavage for 30 days. Morris water maze test (MWM) was performed to assess the effects of I. germanica on learning ...

  15. Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo

    NARCIS (Netherlands)

    Elassiuty, Yasser E.; Klarquist, Jared; Speiser, Jodi; Yousef, Randa M.; El Refaee, Abdelaziz A.; Hunter, Nahla S.; Shaker, Olfat G.; Gundeti, Mohan; Nieuweboer-Krobotova, Ludmila; Caroline Le Poole, I.

    2011-01-01

    To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP.

  16. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  17. Protective effect of metalloporphyrins against cisplatin-induced kidney injury in mice.

    Directory of Open Access Journals (Sweden)

    Hao Pan

    Full Text Available Oxidative and nitrative stress is a well-known phenomenon in cisplatin-induced nephrotoxicity. The purpose of this work is to study the role of two metalloporphyrins (FeTMPyP and MnTBAP, water soluble complexes, in cisplatin-induced renal damage and their ability to scavenge peroxynitrite. In cisplatin-induced nephropathy study in mice, renal nitrative stress was evident by the increase in protein nitration. Cisplatin-induced nephrotoxicity was also evident by the histological damage from the loss of the proximal tubular brush border, blebbing of apical membranes, tubular epithelial cell detachment from the basement membrane, or intra-luminal aggregation of cells and proteins and by the increase in blood urea nitrogen and serum creatinine. Cisplatin-induced apoptosis and cell death as shown by Caspase 3 assessments, TUNEL staining and DNA fragmentation Cisplatin-induced nitrative stress, apoptosis and nephrotoxicity were attenuated by both metalloporphyrins. Heme oxygenase (HO-1 also plays a critical role in metalloporphyrin-mediated protection of cisplatin-induced nephrotoxicity. It is evident that nitrative stress plays a critical role in cisplatin-induced nephrotoxicity in mice. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration and cisplatin-induced nephrotoxicity can be prevented with the use of metalloporphyrins.

  18. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Mattson, Mark P. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Camandola, Simonetta, E-mail: camandolasi@mail.nih.gov [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)

    2013-04-19

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.

  19. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.B.R. Colombo

    2015-01-01

    Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

  20. Riluzole protects against glutamate-induced slowing of neurofilament axonal transport.

    LENUS (Irish Health Repository)

    Stevenson, Alison

    2009-04-24

    Riluzole is the only drug approved for the treatment of amyotrophic lateral sclerosis (ALS) but its precise mode of action is not properly understood. Damage to axonal transport of neurofilaments is believed to be part of the pathogenic mechanism in ALS and this has been linked to defective glutamate handling and increased phosphorylation of neurofilament side-arm domains. Here, we show that riluzole protects against glutamate-induced slowing of neurofilament transport. Protection is associated with decreased neurofilament side-arm phosphorylation and inhibition of the activities of two neurofilament kinases, ERK and p38 that are activated in ALS. Thus, the anti-glutamatergic properties of riluzole include protection against glutamate-induced changes to neurofilament phosphorylation and transport.

  1. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    International Nuclear Information System (INIS)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H.; Mattson, Mark P.; Camandola, Simonetta

    2013-01-01

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity

  2. Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis in rats

    International Nuclear Information System (INIS)

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio

    2006-01-01

    Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: reduction in number of apoptotic colonic crypt cells; reduction in number of caspase-3 positive cells; decreases in p53 accumulation and p21 expression; decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region. (author)

  3. Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.

    Science.gov (United States)

    Wu, Chun Fu; Liu, Yan Li; Song, Ming; Liu, Wen; Wang, Jin Hui; Li, Xian; Yang, Jing Yu

    2003-08-01

    In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

  4. Protective Effect of Wheat Peptides against Indomethacin-Induced Oxidative Stress in IEC-6 Cells

    Directory of Open Access Journals (Sweden)

    Hong Yin

    2014-01-01

    Full Text Available Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.

  5. Effect of top ligament blanking on reducing flow induced vibration of protective grid

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Kyong Bo; Ryu, Joo Young; Kwon, Oh Joon; Park, Joon Kyoo; Jeon, Sang Youn; Suh, Jung Min [KEPCO NF Co., Daejeon (Korea, Republic of)

    2012-10-15

    The protective grid is a Inconel 718 spacer grid located just above the bottom nozzle in many kinds of fuel assemblies for PWR. The purpose of using protective grid is to capture debris before they flow up into the fuel assembly and get trapped by the other grids causing fuel rod damages as well as to provide support at the lower end plugs of fuel rods. Recently, it has been reported that strap failure has occurred in the protective grids and the flow induced vibration of the strap has resulted in the strap fatigue failure. After the root cause of the protective grid failure was found to be the flow induced vibration of the strap, KEPCO NF has made an effort to find the vibration tendencies of grid strap and draw vibration mitigation concepts of the protective grid strap. The vibration tendency and the effect of the vibration mitigation concept of the protective grid which have been found by the results of the loop tests and simulations in KEPCO NF are presented herein.

  6. Dietary spices protect against hydrogen peroxide-induced DNA damage and inhibit nicotine-induced cancer cell migration.

    Science.gov (United States)

    Jayakumar, R; Kanthimathi, M S

    2012-10-01

    Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H₂O₂ and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 μg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (pspices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    Science.gov (United States)

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  8. Gamma-ray-induced bold seeded early maturing groundnut selections

    Energy Technology Data Exchange (ETDEWEB)

    Manoharan, V; Thangavelu, S [Regional Research Station, Vriddhachalam, Tamil Nadu (India)

    1990-07-01

    Full text: ''Chico'' is an early maturing (85-90 days) erect groundnut (Arachis hypogaea L.) genotype utilised in groundnut improvement to incorporate earliness in high yielding varieties. Though it has high shelling out-turn, its yield potential is low since it has small seeds. Mutation breeding was started with the objective of improving the seed size. In a preliminary experiment, dry seeds were treated with 20, 30, 40 or 50 kR of gamma rays. The M{sub 1} generation was grown during the post rainy season of 1988-1989. The M{sub 2} generation was planted as individual plant progeny rows during the rainy season of 1989. 105 progeny rows were studied, the total number of M{sub 2} plants being 1,730. All the M{sub 2} plants were harvested 90 days after sowing. Seven mutants with bold seed size were obtained. The mutants had 100 kernel weight ranging from 22.2 to 40.4 g compared to 21.1 g of control. The study is in progress. (author)

  9. Gamma-ray-induced bold seeded early maturing groundnut selections

    International Nuclear Information System (INIS)

    Manoharan, V.; Thangavelu, S.

    1990-01-01

    Full text: ''Chico'' is an early maturing (85-90 days) erect groundnut (Arachis hypogaea L.) genotype utilised in groundnut improvement to incorporate earliness in high yielding varieties. Though it has high shelling out-turn, its yield potential is low since it has small seeds. Mutation breeding was started with the objective of improving the seed size. In a preliminary experiment, dry seeds were treated with 20, 30, 40 or 50 kR of gamma rays. The M 1 generation was grown during the post rainy season of 1988-1989. The M 2 generation was planted as individual plant progeny rows during the rainy season of 1989. 105 progeny rows were studied, the total number of M 2 plants being 1,730. All the M 2 plants were harvested 90 days after sowing. Seven mutants with bold seed size were obtained. The mutants had 100 kernel weight ranging from 22.2 to 40.4 g compared to 21.1 g of control. The study is in progress. (author)

  10. Immune protection induced on day 10 following administration of the 2009 A/H1N1 pandemic influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Yizhuo Sun

    Full Text Available BACKGROUND: The 2009 swine-origin influenza virus (S-OIV H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. METHODOLOGY/PRINCIPAL FINDINGS: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose. The sera were collected before Day 0 (pre-vaccination and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%. This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21. However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1 more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2. The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21 than that in Group 2 (geometric mean titer: 70 on Day 21. CONCLUSIONS/SIGNIFICANCE: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a

  11. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    Directory of Open Access Journals (Sweden)

    Aicha Fassi Fihri

    2016-06-01

    Full Text Available Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily; group 2: received oral lead acetate (2 g/kg.b.wt/daily; group 3: treated with oral honey (1g /kg.b.wt/daily and oral lead (2 g/kg.b.wt/daily, and group 4: received oral honey (1 g/kg.b.wt/daily. Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.

  12. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

    Science.gov (United States)

    Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

    2016-01-01

    Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

  13. Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.

    Directory of Open Access Journals (Sweden)

    Kim M Gerecke

    Full Text Available Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF, have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/- with strain-matched wild-type (WT mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.

  14. Protective Activity of Dendropanax Morbifera Against Cisplatin-Induced Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Eun-Sun Kim

    2015-01-01

    Full Text Available Background/Aims: Drug-induced acute kidney injury (AKI has been a severe threat to hospitalized patients, raising the urgent needs to develop strategies to reduce AKI. We investigated the protective activity of Dendropanax morbifera (DP, a medicinal plant which has been widely used to treat infectious and pain diseases, on acute kidney injury (AKI using cisplatin-induced nephropathic models. Methods: Both in vitro renal tubular cells (NRK-52E and in vivo rat models were used to demonstrate the nephroprotective effect of DP. Results: Methanolic extract from DP significantly reduced cisplatin-induced toxicity in renal tubular cells. Through successive liquid extraction, the extract of DP was separated into n-hexane, CHCl3, EtOAc, n-BuOH, and H2O fractions. Among these, the CHCl3 fraction (DPCF was found to be most potent. The protective activity of DPCF was found to be mediated through anti-oxidant, mitochondrial protective, and anti-apoptotic activities. In in vivo rat models of AKI, treatment with DPCF significantly reversed the cisplatin-induced increase in blood urea nitrogen and serum creatinine and histopathologic damage, recovered the level of anti-oxidant enzymes, and inhibited renal apoptosis. Conclusion: We demonstrated that DP extracts decreased cisplatin-induced renal toxicity, indicating its potential to ameliorate drug-associated acute kidney damage.

  15. Protective effect of hemin against cadmium-induced testicular damage in rats

    International Nuclear Information System (INIS)

    Fouad, Amr A.; Qureshi, Habib A.; Al-Sultan, Ali Ibrahim; Yacoubi, Mohamed T.; Ali, Abdellah Abusrie

    2009-01-01

    The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2 mg/kg). Hemin was given for three consecutive days (40 μmol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium

  16. Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

    Science.gov (United States)

    Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

    2015-01-01

    HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

  17. Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

    Directory of Open Access Journals (Sweden)

    Xinhua Zhou

    2015-01-01

    Full Text Available Edaravone (EDA is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA- induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

  18. Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

    International Nuclear Information System (INIS)

    Latchoumycandane, Calivarathan; Seah, Quee Ming; Tan, Rachel C.H.; Sattabongkot, Jetsumon; Beerheide, Walter; Boelsterli, Urs A.

    2006-01-01

    Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell-mediated liver injury by poorly understood mechanisms. The active metabolite of leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated protein kinases (JNK pathway), which are key regulators of mitochondria-mediated cell death. Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway. To this end, we exposed cultured immortalized human hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which induces CsA-sensitive mPT-mediated cell death. We determined the effects of leflunomide on the extent of APAP-induced hepatocyte injury and the upstream JNK-mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726 concentration-dependently protected hepatocytes from APAP (1 mM)-induced mitochondrial permeabilization and lethal cell injury. This was not due to proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive metabolite. Instead, we demonstrate that leflunomide (20 μM) inhibited the APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2-mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c release, which we used as a marker for mitochondrial permeabilization. The specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell death. In conclusion, these findings are consistent with our hypothesis that leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK signaling and preventing mPT induction

  19. Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Fen; Sun, Hong; Kluz, Thomas; Clancy, Hailey A.; Kiok, Kathrin; Costa, Max, E-mail: Max.Costa@nyumc.org

    2012-01-15

    Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitative measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K{sup +}/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA–protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis. -- Highlights: ► EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death and apoptosis. ► EGCG significantly decreased

  20. Protective effects of edaravone combined puerarin on inhalation lung injury induced by black gunpowder smog.

    Science.gov (United States)

    Wang, Zhengguan; Li, Ruibing; Liu, Yifan; Liu, Xiaoting; Chen, Wenyan; Xu, Shumin; Guo, Yuni; Duan, Jinyang; Chen, Yihong; Wang, Chengbin

    2015-05-01

    The present study aimed to investigate the combined effects of puerarin with edaravone on inhalation lung injury induced by black gunpowder smog. Male Wistar rats were divided into five groups (control group, edaravone group, puerarin group, edaravone combined with puerarin group and inhalation group). The severity of pulmonary injuries was evaluated after inducing acute lung injury. Arterial blood gas, inflammatory cytokines, biochemical, parameters, cell counting, W/D weight ratio and histopathology were analyzed. Results in lung tissues, either edaravone or puerarin treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis (all pedaravone and puerarin demonstrated additive protective effects on smog-induced lung injury, compared with single treatment. Combination of edaravone and puerarin shows promise as a new treatment option for acute lung injury/acute respiratory distress syndrome patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Taurine Protects Lens Epithelial Cells Against Ultraviolet B-Induced Apoptosis.

    Science.gov (United States)

    Dayang, Wu; Dongbo, Pang

    2017-10-01

    The massive uptake of compatible osmolytes is a self-protective response shared by lens exposed to hypertonic stress and ultraviolet stress. This study aimed to investigate the protective effects of taurine against ultraviolet B-induced cytotoxicity in the lens epithelial cells. Real-time PCR was used to measure osmolytes transport. Radioimmunoassay was used to measure osmolytes uptake. Cell counting kit-8 assays were used to measure cellular viability. Flow cytometry analysis was used to measure apoptosis level. Compared with normotonic stress, hypertonic stress-induced osmolytes uptake into the lens epithelial cells such as betaine, myoinositol and taurine. UVB exposure increased osmolytes transporter mRNA expression together with osmolytes uptake. Moreover, taurine suppressed UVB-induced cell apoptosis in the lens epithelial cells significantly. The effect of compatible osmolyte taurine on cell survival rate may play an important role in cell resistance and adaption to UVB exposure.

  2. UV-blocking spectacle lens protects against UV-induced decline of visual performance.

    Science.gov (United States)

    Liou, Jyh-Cheng; Teng, Mei-Ching; Tsai, Yun-Shan; Lin, En-Chieh; Chen, Bo-Yie

    2015-01-01

    Excessive exposure to sunlight may be a risk factor for ocular diseases and reduced visual performance. This study was designed to examine the ability of an ultraviolet (UV)-blocking spectacle lens to prevent visual acuity decline and ocular surface disorders in a mouse model of UVB-induced photokeratitis. Mice were divided into 4 groups (10 mice per group): (1) a blank control group (no exposure to UV radiation), (2) a UVB/no lens group (mice exposed to UVB rays, but without lens protection), (3) a UVB/UV400 group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [UV400 coating]), and (4) a UVB/photochromic group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [photochromic coating]). We investigated UVB-induced changes in visual acuity and in corneal smoothness, opacity, and lissamine green staining. We also evaluated the correlation between visual acuity decline and changes to the corneal surface parameters. Tissue sections were prepared and stained immunohistochemically to evaluate the structural integrity of the cornea and conjunctiva. In blank controls, the cornea remained undamaged, whereas in UVB-exposed mice, the corneal surface was disrupted; this disruption significantly correlated with a concomitant decline in visual acuity. Both the UVB/UV400 and UVB/photochromic groups had sharper visual acuity and a healthier corneal surface than the UVB/no lens group. Eyes in both protected groups also showed better corneal and conjunctival structural integrity than unprotected eyes. Furthermore, there were fewer apoptotic cells and less polymorphonuclear leukocyte infiltration in corneas protected by the spectacle lenses. The model established herein reliably determines the protective effect of UV-blocking ophthalmic biomaterials, because the in vivo protection against UV-induced ocular damage and visual acuity decline was easily defined.

  3. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Science.gov (United States)

    Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

    2013-04-01

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  4. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Faddah, L. M.; Baky, Nayira A. Abdel [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia); Mohamed, Azza M., E-mail: azzamohamed99@yahoo.com [King Abdulaziz University, Biochemistry Department, Faculty of Science for Girls (Saudi Arabia); Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M. [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia)

    2013-04-15

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-{alpha}, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  5. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

    International Nuclear Information System (INIS)

    Zhang, Da-Gang; Zhang, Cheng; Wang, Jun-Xian; Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua; Lu, Yan; Tao, Li; Wang, Jian-Qing; Chen, Xi; Xu, De-Xiang

    2017-01-01

    The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl 4 )-induced acute liver injury. Mice were intraperitoneally injected with CCl 4 (0.15 ml/kg). In CCl 4 + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl 4 . As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl 4 -induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl 4 -induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl 4 -induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl 4 -induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl 4 -induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl 4 -induced acute liver injury. These results suggest that OCA protects against CCl 4 -induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl 4 -induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl 4 -induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.

  6. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Da-Gang [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei 230032 (China); Wang, Jun-Xian [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua [Department of Toxicology, Anhui Medical University, Hefei 230032 (China); Lu, Yan; Tao, Li; Wang, Jian-Qing [Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Xu, De-Xiang, E-mail: xudex@126.com [Department of Toxicology, Anhui Medical University, Hefei 230032 (China)

    2017-01-01

    The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.

  7. TRMM Applications for Rainfall-Induced Landslide Early Warning

    Science.gov (United States)

    Dok, A.; Fukuoka, H.; Hong, Y.

    2012-04-01

    Early warning system (EWS) is the most effective method in saving lives and reducing property damages resulted from the catastrophic landslides if properly implemented in populated areas of landslide-prone nations. For predicting the occurrence of landslides, it requires examination of empirical relationship between rainfall characteristics and past landslide occurrence. In developed countries like Japan and the US, precipitation is monitored by rain radars and ground-based rain gauge matrix. However, in developing regions like Southeast Asian countries, very limited number of rain gauges is available, and there is no implemented methodology for issuing effective warming of landslides yet. Correspondingly, satellite precipitation monitoring could be therefore a possible and promising solution for launching landslide quasi-real-time early warning system in those countries. It is due to the fact that TMPA (TRMM Multi-satellite Precipitation Analysis) can provides a globally calibration-based sequential scheme for combining precipitation estimates from multiple satellites, and gauge analyses where feasible, at fine scales (3-hourly with 0.25°x0.25° spatial resolution). It is available both after and in quasi-real time, calibrated by TRMM Combined Instrument and TRMM Microwave Imager precipitation product. However, validation of ground based rain gauge and TRMM satellite data in the vulnerable regions is still not yet operative. Snake-line/Critical-line and Soil Water Index (SWI) are used for issuing warning of landslide occurrence in Japan; whereas, Caine criterion is preferable in Europe and western nations. Herewith, it presents rainfall behavior which took place in Beichuan city (located on the 2008 Chinese Wenchuan earthquake fault), Hofu and Shobara cities in Japan where localized heavy rainfall attacked in 2009 and 2010, respectively, from TRMM 3B42RT correlated with ground based rain gauge data. The 1-day rainfall intensity and 15-day cumulative rainfall

  8. Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State.

    Science.gov (United States)

    Belkacemi, Abdenour; Ramassamy, Charles

    2016-01-01

    In Alzheimer's disease (AD) and in mild cognitive impairment (MCI) patients, by-products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox-sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-β-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5μM, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-κB and Nrf2, the proteins γ-GCS and GSK3β, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-β toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention.

  9. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-09

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  10. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  11. Immune markers and correlates of protection for vaccine induced immune responses

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Pedersen, Lasse Eggers; Jungersen, Gregers

    2012-01-01

    of an appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against......-specific production of interferon-gamma (IFN-γ) has been promoted as a quantitative marker of protective cell-mediated immune responses over the past couple of decades. More recently, however, evidence from several infections has pointed towards the quality of the immune response, measured through increased levels...... of antigen-specific polyfunctional T cells capable of producing a triad of relevant cytokines, as a better correlate of sustained protective immunity against this type of infections. Also the possibilities to measure antigen-specific cytotoxic T cells (CTL) during infection or in response to vaccination...

  12. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    James Crooks

    2017-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

  13. Angiotensin II protects primary rat hepatocytes against bile salt-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Golnar Karimian

    Full Text Available UNLABELLED: Angiotensin II (AT-II is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R and thereby activates hepatic stellate cells (HSCs. AT-II receptor blockers (ARBs are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that AT-1R blockers may induce hepatocyte injury. Therefore, we investigated the effect of AT-II and its receptor blockers on cytokine-, oxidative stress- and bile salt-induced cell death in hepatocytes. Primary rat hepatocytes were exposed to TNF-α/Actinomycin D, the ROS-generating agent menadione or the bile salts: glycochenodeoxycholic acid (GCDCA and tauro-lithocholic acid-3 sulfate (TLCS, to induce apoptosis. AT-II (100 nmol/L was added 10 minutes prior to the cell death-inducing agent. AT-1R antagonists (Sartans and the AT-2R antagonist PD123319 were used at 1 µmol/L. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (Sytox green staining were quantified. Expression of CHOP (marker for ER stress and AT-II receptor mRNAs were quantified by Q-PCR. AT-II dose-dependently reduced GCDCA-induced apoptosis of hepatocytes (-50%, p<0.05 without inducing necrosis. In addition, AT-II reduced TLCS-induced apoptosis of hepatocytes (-50%, p<0.05. However, AT-II did not suppress TNF/Act-D and menadione-induced apoptosis. Only the AT-1R antagonists abolished the protective effect of AT-II against GCDCA-induced apoptosis. AT-II increased phosphorylation of ERK and a significant reversal of the protective effect of AT-II was observed when signaling kinases, including ERK, were inhibited. Moreover, AT-II prevented the GCDCA-induced expression of CHOP (the marker of the ER-mediated apoptosis. CONCLUSION: Angiotensin II protects hepatocytes from bile salt-induced apoptosis through a combined activation of PI3-kinase, MAPKs, PKC pathways and inhibition of bile salt-induced ER stress. Our results suggest a mechanism for the observed hepatocyte

  14. Protective effects of red wine flavonols on 4-hydroxynonenal-induced apoptosis in PC12 cells.

    Science.gov (United States)

    Jang, Young Jin; Kang, Nam Joo; Lee, Ki Won; Lee, Hyong Joo

    2009-08-01

    There is accumulating evidence that a moderate consumption of red wine has health benefits, such as the inhibition of neurodegenerative diseases. Although this is generally attributed to resveratrol, the protective mechanisms and the active substance(s) remain unclear. We examined whether and how red wine extract (RWE) and red wine flavonols quercetin and myricetin inhibited 4-hydroxynonenal (HNE)-induced apoptosis of rat pheochromocytoma PC12 cells. RWE attenuated HNE-induced PC12 cell death in a dose-dependent manner. HNE induced cleavage of poly(ADP-ribose) polymerase, which is involved in DNA repair in the nucleus, and this was inhibited by RWE treatment. Treatment with RWE also inhibited HNE-induced nuclear condensation in PC12 cells. Data of 2',7'-dichlorofluorescin diacetate showed that RWE protected against apoptosis of PC12 cells by attenuating intracellular reactive oxygen species. The cytoprotective effects on HNE-induced cell death were stronger for quercetin and myricetin than for resveratrol. HNE-induced nuclear condensation was attenuated by quercetin and myricetin. These results suggest that the neuroprotective potential of red wine is attributable to flavonols rather than to resveratrol.

  15. Protective effect of arctigenin on ethanol-induced neurotoxicity in PC12 cells.

    Science.gov (United States)

    Huang, Jia; Xiao, Lan; Wei, Jing-Xiang; Shu, Ya-Hai; Fang, Shi-Qi; Wang, Yong-Tang; Lu, Xiu-Min

    2017-04-01

    As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine‑induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons. As a result, it may offer beneficial effects on ethanol-induced neurotoxicity. However, the effects of ATG on ethanol‑induced nerve damage remain to be elucidated. To address this issue, the present study used rat pheochromocytoma PC12 cells to investigate the neuroprotective effects of ATG on ethanol-induced cell damage by performing an MTT reduction assay, cell cycle analysis, Hoechst33342/propidium iodide fluorescence staining and flow cytometry to examine apoptosis. The results showed that 10 µM ATG effectively promoted the proliferation of damaged cells, and increased the distribution ratio of the cells at the G2/M and S phases (P<0.05). In addition, the apoptosis and necrosis of the PC12 cells were significantly decreased following treatment with ATG. Therefore, it was concluded that 10 µM ATG had a protective effect on ethanol‑induced injury in PC12 cells.

  16. 19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Elkhatali, Samya; El-Sherbeni, Ahmed A.; Elshenawy, Osama H. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Abdelhamid, Ghada [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan (Egypt); El-Kadi, Ayman O.S., E-mail: aelkadi@ualberta.ca [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada)

    2015-12-15

    We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague–Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200 mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography–mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. - Highlights: • We found 19-hydroxy arachidonic acid to protect cardiomyocytes from hypertrophy. • We validated the use of isoniazid as a cardiac 19-hydroxy arachidonic acid inducer. • We found isoniazid to increase protective and inhibit toxic eicosanoides. • We found isoniazid to protect against angiotensin-induced cardiac hypertrophy. • This will help to

  17. Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.

    Science.gov (United States)

    Xiong, Xi; Ren, Yuqian; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai

    2017-12-01

    Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Protective effects of ebselen on sodium-selenite-induced experimental cataract in rats.

    Science.gov (United States)

    Aydemir, Orhan; Güler, Mete; Kaya, Mehmet Kaan; Deniz, Nurettin; Üstündağ, Bilal

    2012-12-01

    To determine whether ebselen has a protective effect or antioxidative potential in a sodium-selenite-induced experimental cataract model. Fırat University, Elazığ, Turkey. Experimental study. Twenty-one Sprague-Dawley rat pups were randomly divided into a control group, a sodium-selenite-induced-cataract group, and an ebselen-treated group; each group contained 7 rat pups. Rats in the control group received dimethyl sulfoxide (DMSO) intraperitoneally only and rats in the sodium-selenite-induced-cataract group received 30 nmol/g body weight sodium selenite subcutaneously and DMSO intraperitoneally 10 days postpartum. Rats in the ebselen group received 30 nmol/g body weight sodium selenite subcutaneously 10 days postpartum and were treated with 5 mg/kg body weight ebselen once a day for 4 consecutive days. Cataract development was assessed weekly for 3 weeks by slitlamp examination and graded using a scale. Reduced glutathione (GSH), total nitrite, and malondialdehyde (MDA) levels in lens supernatants were measured at the end of 3 weeks. In the control group, all lenses were clear. In the ebselen-treated group, the mean cataract stage was significantly lower than in the sodium-selenite-induced-cataract group (P = .022). The GSH levels were significantly lower in the sodium-selenite-induced-cataract group than in the control and ebselen groups (P ebselen group than in the sodium-selenite-induced-cataract group (P ebselen group (P = .001). Ebselen had a protective effect on cataract development in a sodium-selenite-induced experimental model. The protective effect of ebselen appears to be due to inhibition of oxidative stress. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  19. Protective Efficacy of Emodin against γ-Rays Induced Acute Hepatorenal Injury in Rats

    International Nuclear Information System (INIS)

    Ibrahim, S.I.; Lotfi, S.A.

    2011-01-01

    Emodin(C 16 H 12 O 5 ), an active principle extracted from Rheum palmatum. Its protective effect was evaluated against γ-rays-induced biochemical alterations in rats. The purpose of recent study is to demonstrate protective efficacy of emodin against γ-rays induced acute hepatorenal injury in rats.γ -irradiation (6 Gy) caused significant elevation in the release of serum alanine and aspartate transaminases, (ALT and AST), alkaline phosphatase (SALP), lactate dehydrogenase (LDH), bilirubin (Br) and glucose (Gu) with concomitant decrease in haemoglobin (Hb) after 24 h of its exposure. Toxicant exposure intensified the lipid peroxidation (LPO, measured as MDA units), total cholesterol (TC) and activity of acid phosphatase (TAC) and altered glutathione status (GSH), activities of adenosine triphosphatase (ATP), alkaline phosphatase (TALP), glutamate dehydrogenase (GDH) as well as major cellular constituents; total proteins (TP) and glycogen (Gn) in liver and kidney, compared to control measures. Emodin, oral treatment, significantly lessened the toxicity by protecting γ-rays-induced alterations in various blood and tissue biochemical variables, compared to irradiated groups. Thus, the study concluded that emodin at a dose of 40 mg/ kg body wt possesses optimum hepatorenal protective ability in γ-irradiated toxicant rats

  20. The protective effect of Sambucus ebulus against lung toxicity induced by gamma irradiation in mice

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    Mohammad Karami

    2015-01-01

    Full Text Available The aim of present study was to investigate the potential antioxidant and lung protective activities of Sambucus ebulus (SE against toxicity induced by gamma irradiation. Hydroalcoholic extract of SE (20, 50 and 100 mg/kg was studied for its lung protective activity. Phenol and flavonoid contents of SE were determined. Male C57 mice were divided into ten groups with five mice per group. Only the first and second groups (as negative control received intraperitoneally normal saline fluid. Groups 3 to 5 received only SE extract at doses of 20 mg/kg, 50 mg/kg and 100 mg/kg intraperitoneally; three groups were repeatedly injected for 15 days as chronic group. Groups 6 to 8 received a single-dose of gamma irradiation just 2 hours before irradiation as acute group. The ninth and tenth groups (as positive control received only gamma rays. Animal was exposed whole-body to 6 Gy gamma radiation. After irradiation, tissue sections of lung parenchyma were examined by light microscope for any histopathologic changes. SE at doses 50 and 100 mg/kg improved markedly histopathological changes induced by gamma irradiation in lung. Lung protective effect of SE could be due to attention of lipid peroxidation. Our study demonstrated that SE as a natural product has a protective effect against lung toxicity induced by   gamma irradiation in animal.

  1. Exercise-induced circulating extracellular vesicles protect against cardiac ischemia-reperfusion injury.

    Science.gov (United States)

    Bei, Yihua; Xu, Tianzhao; Lv, Dongchao; Yu, Pujiao; Xu, Jiahong; Che, Lin; Das, Avash; Tigges, John; Toxavidis, Vassilios; Ghiran, Ionita; Shah, Ravi; Li, Yongqin; Zhang, Yuhui; Das, Saumya; Xiao, Junjie

    2017-07-01

    Extracellular vesicles (EVs) serve an important function as mediators of intercellular communication. Exercise is protective for the heart, although the signaling mechanisms that mediate this cardioprotection have not been fully elucidated. Here using nano-flow cytometry, we found a rapid increase in plasma EVs in human subjects undergoing exercise stress testing. We subsequently identified that serum EVs were increased by ~1.85-fold in mice after 3-week swimming. Intramyocardial injection of equivalent quantities of EVs from exercised mice and non-exercised controls provided similar protective effects against acute ischemia/reperfusion (I/R) injury in mice. However, injection of exercise-induced EVs in a quantity equivalent to the increase seen with exercise (1.85 swim group) significantly enhanced the protective effect. Similarly, treatment with exercise-induced increased EVs provided additional anti-apoptotic effect in H 2 O 2 -treated H9C2 cardiomyocytes mediated by the activation of ERK1/2 and HSP27 signaling. Finally, by treating H9C2 cells with insulin-like growth factor-1 to mimic exercise stimulus in vitro, we found an increased release of EVs from cardiomyocytes associated with ALIX and RAB35 activation. Collectively, our results show that exercise-induced increase in circulating EVs enhances the protective effects of endogenous EVs against cardiac I/R injury. Exercise-derived EVs might serve as a potent therapy for myocardial injury in the future.

  2. Skin protection against UVA-induced iron damage by multiantioxidants and iron chelating drugs/prodrugs.

    Science.gov (United States)

    Reelfs, Olivier; Eggleston, Ian M; Pourzand, Charareh

    2010-03-01

    In humans, prolonged sunlight exposure is associated with various pathological states. The continuing drive to develop improved skin protection involves not only approaches to reduce DNA damage by solar ultraviolet B (UVB) but also the development of methodologies to provide protection against ultraviolet A (UVA), the oxidising component of sunlight. Furthermore identification of specific cellular events following ultraviolet (UV) irradiation is likely to provide clues as to the mechanism of the development of resulting pathologies and therefore strategies for protection. Our discovery that UVA radiation, leads to an immediate measurable increase in 'labile' iron in human skin fibroblasts and keratinocytes provides a new insight into UVA-induced skin damage, since iron is a catalyst of biological oxidations. The main purpose of this overview is to bring together some of the new findings related to mechanisms underlying UVA-induced iron release and to discuss novel approaches based on the use of multiantioxidants and light-activated caged-iron chelators for efficient protection of skin cells against UVA-induced iron damage.

  3. Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

    Directory of Open Access Journals (Sweden)

    Upa Kukongviriyapan

    2014-03-01

    Full Text Available Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L in drinking water for eight weeks. Curcumin (50 or 100 mg/kg was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.

  4. Far red/near infrared light-induced protection against cardiac ischemia and reperfusion injury remains intact under diabetic conditions and is independent of nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Agnes eKeszler

    2014-08-01

    Full Text Available Far red/near-infrared light (NIR promotes a wide range of biological effects including tissue protection but whether and how NIR is capable of acutely protecting myocardium against ischemia and reperfusion injury in vivo is not fully elucidated. Our previous work indicates that NIR exposure immediately before and during early reperfusion protects the myocardium against infarction through mechanisms that are nitric oxide (NO-dependent. Here we tested the hypothesis that NIR elicits protection in a diabetic mouse model where other cardioprotective interventions such as pre- and postconditioning fail, and that the protection is independent of nitric oxide synthase (NOS. NIR reduced infarct size dose dependently. Importantly, NIR-induced protection was preserved in a diabetic mouse model (db/db and during acute hyperglycemia, as well as in endothelial NOS-/- mice and in wild type mice treated with NOS inhibitor L-NAME. In in vitro experiments NIR light liberates NO from nitrosyl hemoglobin (HbNO and nitrosyl myoglobin (MbNO in a wavelength (660-830 nm and dose-dependent manner. Irradiation at 660 nm yields the highest release of NO, while at longer wavelengths a dramatic decrease of NO release can be observed. Similar wavelength dependence was observed for the protection of mice against cardiac ischemia and reperfusion injury in vivo. NIR-induced NO release from deoxymyoglobin in the presence of nitrite mildly inhibits respiration of isolated mitochondria after hypoxia. In summary, NIR applied during reperfusion protects the myocardium against infarction in an NO dependent, but NOS-independent mechanisms, whereby mitochondria may be a target of NO released by NIR, leading to reduced reactive oxygen species generation during reperfusion. This unique mechanism preserves protection even during diabetes where other protective strategies fail.

  5. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    Directory of Open Access Journals (Sweden)

    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  6. The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Ana Cardoso

    2018-03-01

    Full Text Available Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10, described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.

  7. The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

    Science.gov (United States)

    Cardoso, Ana; Gil Castro, Antonio; Martins, Ana Catarina; Carriche, Guilhermina M.; Murigneux, Valentine; Castro, Isabel; Cumano, Ana; Vieira, Paulo; Saraiva, Margarida

    2018-01-01

    Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection. PMID:29545807

  8. Early attentional bias for negative words when competition is induced.

    Science.gov (United States)

    Ho, Ming-Chou; Li, Shuo-Heng; Yeh, Su-Ling

    2016-05-01

    Previous research (Zeelenberg, Wagenmakers, & Rotteveel, 2006) revealed that emotionally meaningful words were identified significantly better than neutral words, with no difference between positive and negative words. Since in that study only a single target word was displayed at a time, we hypothesized that the equivalent performances for positive and negative words were due to a lack of competition. To test this, in our Experiment 1, we replicated Zeelenberg and colleagues' finding, using emotion-laden Chinese words and the identical data-limited method, which measured the accuracy of a briefly shown target. We then introduced competition in Experiment 2 by simultaneously presenting two words during the target frame, and found evidence for an early attentional bias to negative words. In Experiment 3, we confirmed that the bias in Experiment 2 was not due to the inevitable repetition of stimuli. Taken together, these results support our hypothesis that, in the presence of competition, negative words receive attentional priority and consequently have enhanced perceptual representations.

  9. The use of suction blisters to measure sunscreen protection against UVR-induced DNA damage.

    Science.gov (United States)

    Josse, Gwendal; Douki, Thierry; Le Digabel, Jimmy; Gravier, Eleonore; Questel, Emmanuel

    2018-02-01

    The formation of DNA photoproducts caused by solar UVR exposure needs to be investigated in-vivo and in particular in order to assess sunscreens' level of protection against solar genotoxicity. The study's purposes were: i) to evaluate if the roof of suction blisters is an appropriate sampling method for measuring photoproducts, and ii) to measure in-vivo sunscreen protection against cyclobutane pyrimidine dimers. Skin areas on the interior forearms of eight healthy volunteers were exposed in-vivo to 2 MED of simulated solar radiation (SSR) and to 15 MED on a sunscreen protected area. After irradiation, six suction blisters were induced and the blister roofs were collected. Analysis of SSR-induced CPDs was performed by two independent methods: a chromatography coupled to mass spectroscopy (HPLC-MS/MS) approach and a 3D-imaging of CPD immunostaining by multiphoton microscopy on floating epidermal sheets. HPLC-MS/MS analyses showed that SSR-unexposed skin presented no CPD dimers, whereas 2 MED SSR-exposed skin showed a significant number of TT-CPD. The sunscreen covered skin exposed to 15 MED appeared highly protected from DNA damage, as the amount of CPD-dimers remained below the detection limit. The multiphoton-immunostaining analysis consistently showed that no CPD staining was observed on the non-SSR-exposed skin. A significant increase of CPD staining intensity and number of CPD-positive cells were observed on the 2 MED SSR-exposed skin. Sunscreen protected skin presented a very low staining intensity and the number of CPD-positive cells remained very close to non-SSR-exposed skin. This study showed that suction blister samples are very appropriate for measuring CPD dimers in-vivo, and that sunscreens provide high protection against UVR-induced DNA damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    Directory of Open Access Journals (Sweden)

    Yao Xin-Sheng

    2011-10-01

    Full Text Available Abstract Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD and glutathione peroxidase (GPx activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process.

  11. Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma.

    Science.gov (United States)

    Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

    2017-09-01

    Rationale of this study was framed to investigate the protective effect and anti-cancer property of nanoparticles based on chitosan isolated from squid, Sepioteuthis lessoniana, on hepatic cells in N-Nitrosodiethylamine-induced hepatocellular carcinoma in rats. The results conferred that the chitosan nanoparticle supplementation had a protective effect on liver cells by reducing the levels of marker enzymes and bilirubin and thus increasing the albumin levels. The level of reduced glutathione, ascorbic acid and α-tocopherol significantly increased in both post- and pre-treatment with chitosan nanoparticles. The levels of antioxidant enzymes were enhanced and lipid peroxidation products were diminished while treating nitrosodiethylamine-induced hepatocellular carcinoma with chitosan nanoparticles. Supplementation of chitosan nanoparticles had potent anti-hyperlipidemic property that was evidenced by monitoring the serum lipid levels and its components. Animals pre-treated with chitosan nanoparticles along with nitrosodiethylamine showed a significant reduction in the total cholesterol and triglycerides levels with increase in the levels of phospholipids and free fatty acids. Chitosan nanoparticles treated rats showed significant increment in high-density lipoprotein cholesterol and reduction in low-density lipoprotein and very low-density lipoprotein cholesterol when compared with levels in nitrosodiethylamine-induced hepatocellular carcinoma. Nitrosodiethylamine-induced carcinoma changes on circulation and hepatic antioxidant defense mechanism were regulated by chitosan nanoparticles, concluding that the chitosan nanoparticles have a potent protective effect on liver cells which might be due to its robust antioxidant and anti-lipidemic property. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Total Flavonoids from Mimosa Pudica Protects Carbon Tetrachloride -Induced Acute Liver Injury in Mice

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    Zhen-qin QIU

    2015-03-01

    Full Text Available Objective: To observe the protective effect of total flavonoids from Mimosa pudica on carbon tetrachloride (CCl4-induced acute liver injury in mice. Methods: CCl4-induced acute liver injury model in mice was established. The activity of ALT and AST, the content of serum albumin (Alb and total antioxidant capacity (T-AOC were determined. The content of malondiadehyde (MDA was measured and the activity of superoxide dismutase (SOD was determined. The histopathological changes of liver were observed.Results: Compared with CCl4 modle group, each dose group of total flavonouida from Mimosa pudica couldreduced the activity of ALT and AST in mice obviously (P<0.01, indicating they had remarkably protective effect on CCl4-induced acute liver injury in mice. high and middle dose groups of total flavonouida from Mimosa pudica couldincrease the content of Alb in mice (P<0.01. Each dose group of total flavonouida from Mimosa pudica could enhance the level of T-AOC (P<0.01. each dose group of total flavonouida from Mimosa pudica could lower the content of liver homogenate MDA but enhance the activity of SOD in a dose-depended manner (P<0.01. Conclusion: Total flavones from Mimosa Pudica have obvious protective effect on CCl4-induced acute liver injury in mice.

  13. Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress

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    Wei Chen

    2017-01-01

    Full Text Available Ethyl carbamate (EC is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH depletion and caused mitochondrial membrane potential (MMP collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress.

  14. Britanin Ameliorates Cerebral Ischemia-Reperfusion Injury by Inducing the Nrf2 Protective Pathway.

    Science.gov (United States)

    Wu, Guozhen; Zhu, Lili; Yuan, Xing; Chen, Hao; Xiong, Rui; Zhang, Shoude; Cheng, Hao; Shen, Yunheng; An, Huazhang; Li, Tiejun; Li, Honglin; Zhang, Weidong

    2017-10-10

    Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators and test their neuronal protective activity both in vivo and in vitro. The herb-derived compound, Britanin, is a potent inducer of the Nrf2 system. Britanin can induce the expression of protective enzymes and reverse oxygen-glucose deprivation, followed by reperfusion (OGD-R)-induced neuronal injury in primary cortical neurons in vitro. Furthermore, the administration of Britanin significantly ameliorated middle cerebral artery occlusion-reperfusion (MCAO-R) insult in vivo. We report here the crystal structure of the complex of Britanin and the BTB domain of Keap1. Britanin selectively binds to a conserved cysteine residue, cysteine 151, of Keap1 and inhibits Keap1-mediated ubiquitination of Nrf2, leading to induction of the Nrf2 pathway. Britanin is a potent inducer of Nrf2. The complex crystal structure of Britanin and the BTB domain of Keap1 help clarify the mechanism of Nrf2 induction. Britanin was proven to protect primary cortical neurons against OGD-R-induced injury in an Nrf2-dependant way. Additionally, Britanin had excellent cerebroprotective effect in an MCAO-R model. Our results demonstrate that the natural product Britanin with potent Nrf2-activating and neural protective activities both in vitro and in vivo could be developed into a cerebroprotective therapeutic agent. Antioxid. Redox Signal. 27, 754-768.

  15. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy

    OpenAIRE

    Davenport, Ross; Brohi, Karim

    2013-01-01

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen con...

  16. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy.

    Science.gov (United States)

    Davenport, Ross; Brohi, Karim

    2013-09-24

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen concentrate or cryoprecipitate should be considered a clinical priority in major trauma hemorrhage.

  17. A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

    Science.gov (United States)

    Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

    2009-09-01

    Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

  18. Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite).

    Science.gov (United States)

    Silva, Victor D A; Cuevas, Carlos; Muñoz, Patricia; Villa, Monica; Ahumada-Castro, Ulises; Huenchuguala, Sandro; Santos, Cleonice C Dos; Araujo, Fillipe M DE; Ferreira, Rafael S; Silva, Vanessa B DA; Silva, Juliana H C E; Soares, Érica N; Velozo, Eudes S; Segura-Aguilar, Juan; Costa, Silvia L

    2017-01-01

    Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7.5 µg/mL) induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

  19. Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite

    Directory of Open Access Journals (Sweden)

    VICTOR D.A. SILVA

    Full Text Available ABSTRACT Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD and autophagy on the mechanism of cell death induced by a total extract (TAE of alkaloids and fraction (F32 from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL and F32 (7.5 µg/mL induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

  20. Investigation of protection problems due to geomagnetically induced currents (solar magnetic disturbances, transformers)

    International Nuclear Information System (INIS)

    1997-01-01

    The problems with geomagnetically induced currents (GIC) flowing in power systems during solar magnetic disturbances were studied. Transformers can overheat as a result of GIC because they can cause offset saturation of power system transformers. Harmonic currents can also be introduced into the system which then affect the relay and protection systems. Several studies have been conducted using simplified transformer core models to predict the transformer response to DC excitation. In this study, an accurate transformer core model was developed and validated by comparing the recorded waveforms during GIC events with simulated waveforms using the model. The new transformer core model was used to evaluate the performance of different protection schemes under GIC

  1. Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

    OpenAIRE

    Diaz-San Segundo, Fayna; Dias, Camila C. A.; Moraes, Mauro P.; Weiss, Marcelo; Perez-Martin, Eva; Owens, Gary; Custer, Max; Kamrud, Kurt; de los Santos, Teresa; Grubman, Marvin J.

    2013-01-01

    We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice a...

  2. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway.

    Science.gov (United States)

    Son, Tae Gen; Kawamoto, Elisa M; Yu, Qian-Sheng; Greig, Nigel H; Mattson, Mark P; Camandola, Simonetta

    2013-04-19

    Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity. Published by Elsevier Inc.

  3. Clozapine-Induced Myocarditis: Is Mandatory Monitoring Warranted for Its Early Recognition?

    Directory of Open Access Journals (Sweden)

    T. A. Munshi

    2014-01-01

    Full Text Available Clozapine is an atypical antipsychotic used for treatment resistant schizophrenia. Its potential to induce agranulocytosis is well known but it can also cause myocarditis. Clozapine is the only antipsychotic known to induce this side effect, typically early in the treatment, and literature is scarce on this condition. We are presenting a case report of a 21-year-old schizophrenic male who developed myocarditis within 3 weeks of starting on clozapine for his treatment resistant psychosis. We then aim to review some of the available literature and raise awareness among physicians as this condition can potentially be fatal if not detected early.

  4. Early remodeling of rat cardiac muscle induced by swimming training

    Directory of Open Access Journals (Sweden)

    Verzola R.M.M.

    2006-01-01

    Full Text Available The aim of the present investigation was to study the effect of acute swimming training with an anaerobic component on matrix metallopeptidase (MMP activity and myosin heavy chain gene expression in the rat myocardium. Animals (male Wistar rats, weighing approximately 180 g were trained for 6 h/day in 3 sessions of 2 h each for 1 to 5 consecutive days (N = 5 rats per group. Rats swam in basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35ºC. After the training period a significant increase (P < 0.05 was observed in the heart weight normalized to body weight by about 22 and 35% in the groups that trained for 96 and 120 h, respectively. Blood lactate levels were significantly increased (P < 0.05 in all groups after all training sessions, confirming an anaerobic component. However, lactate levels decreased (P < 0.05 with days of training, suggesting that the animals became adapted to this protocol. Myosin heavy chain-ß gene expression, analyzed by real time PCR and normalized with GAPDH gene expression, showed a significant two-fold increase (P < 0.01 after 5 days of training. Zymography analysis of myocardium extracts indicated a single ~60-kDa activity band that was significantly increased (P < 0.05 after 72, 96, and 120 h, indicating an increased expression of MMP-2 and suggesting precocious remodeling. Furthermore, the presence of MMP-2 was confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3. Taken together, our results indicate that in these training conditions, the rat heart undergoes early biochemical and functional changes required for the adaptation to the new physiological condition by tissue remodeling.

  5. Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

    Science.gov (United States)

    Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

    2010-01-01

    Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage. 2010 S. Karger AG, Basel.

  6. Environmental enrichment protects spatial learning and hippocampal neurons from the long-lasting effects of protein malnutrition early in life.

    Science.gov (United States)

    Soares, Roberto O; Horiquini-Barbosa, Everton; Almeida, Sebastião S; Lachat, João-José

    2017-09-29

    As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro

    Directory of Open Access Journals (Sweden)

    Wang Wen-Ching

    2012-08-01

    Full Text Available Abstract Background Doxorubicin (DOX is an effective antineoplastic drug; however, clinical use of DOX is limited by its dose-dependent cardiotoxicity. It is well known that reactive oxygen species (ROS play a vital role in the pathological process of DOX-induced cardiotoxicity. For this study, we evaluated the protective effects of guggulsterone (GS, a steroid obtained from myrrh, to determine its preliminary mechanisms in defending against DOX-induced cytotoxicity in H9C2 cells. Methods In this study, we used a 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay, lactate dehydrogenase (LDH release measurements, and Hoechst 33258 staining to evaluate the protective effect of GS against DOX-induced cytotoxicity in H9C2 cells. In addition, we observed the immunofluorescence of intracellular ROS and measured lipid peroxidation, caspase-3 activity, and apoptosis-related proteins by using Western blotting. Results The MTT assay and LDH release showed that treatment using GS (1–30 μM did not cause cytotoxicity. Furthermore, GS inhibited DOX (1 μM-induced cytotoxicity in a concentration-dependent manner. Hoechst 33258 staining showed that GS significantly reduced DOX-induced apoptosis and cell death. Using GS at a dose of 10–30 μM significantly reduced intracellular ROS and the formation of MDA in the supernatant of DOX-treated H9C2 cells and suppressed caspase-3 activity to reference levels. In immunoblot analysis, pretreatment using GS significantly reversed DOX-induced decrease of PARP, caspase-3 and bcl-2, and increase of bax, cytochrome C release, cleaved-PARP and cleaved-caspase-3. In addition, the properties of DOX-induced cancer cell (DLD-1 cells death did not interfere when combined GS and DOX. Conclusion These data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.

  8. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Science.gov (United States)

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

  9. Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

    Directory of Open Access Journals (Sweden)

    Sayed M. Mizar

    2015-03-01

    Full Text Available Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg and/or chrysin (25 mg/kg by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT and aspartate transaminase (AST, as well as hepatic Myeloperoxidase (MPO, total nitrate (NOx, glutathione (GSH and liver malondialdehyde (MDA were measured at the end of the experiment. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS subtypes, endothelial (eNOS and inducible (iNOS in liver samples were assessed by Western blotting and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

  10. Creatine affords protection against glutamate-induced nitrosative and oxidative stress.

    Science.gov (United States)

    Cunha, Mauricio P; Lieberknecht, Vicente; Ramos-Hryb, Ana Belén; Olescowicz, Gislaine; Ludka, Fabiana K; Tasca, Carla I; Gabilan, Nelson H; Rodrigues, Ana Lúcia S

    2016-05-01

    Creatine has been reported to exert beneficial effects in several neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative stress play an etiological role. The purpose of this study was to investigate the protective effects of creatine, as compared to the N-Methyl-d-Aspartate (NMDA) receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide (H2O2)-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to glutamate (60-80 mM) or H2O2 (200-300 μM) for 24 h decreased cellular viability and increased dichlorofluorescein (DCF) fluorescence (indicative of increased reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by mono-nitrogen oxides, NOx, levels). Creatine (1-10 mM) or MK-801 (0.1-10 μM) reduced glutamate- and H2O2-induced toxicity. The protective effect of creatine against glutamate-induced toxicity involves its antioxidant effect, since creatine, similar to MK-801, prevented the increase on DCF fluorescence induced by glutamate or H2O2. Furthermore, creatine or MK-801 blocked glutamate- and H2O2-induced increases in NOx levels. In another set of experiments, the repeated, but not acute, administration of creatine (300 mg/kg, po) in mice prevented the decreases on cellular viability and mitochondrial membrane potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of hippocampal slices incubated with glutamate (10 mM). Creatine concentration-dependent decreased the amount of nitrite formed in the reaction of oxygen with NO produced from sodium nitroprusside solution, suggesting that its protective effect against glutamate or H2O2-induced toxicity might be due to its scavenger activity. Overall, the results suggest that creatine may be useful as adjuvant therapy for neurodegenerative disease treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Valsartan Protects Against Contrast-Induced Acute Kidney Injury in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Apoptosis.

    Science.gov (United States)

    Sun, Yan; Peng, Ping-An; Ma, Yue; Liu, Xiao-Li; Yu, Yi; Jia, Shuo; Xu, Xiao-Han; Wu, Si-Jing; Zhou, Yu-Jie

    2017-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers. Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (Pvalsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (PValsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Protective Effect of Bauhinia purpurea on Gentamicin-induced Nephrotoxicity in Rats

    Science.gov (United States)

    Lakshmi, B. V. S.; Neelima, N.; Kasthuri, N.; Umarani, V.; Sudhakar, M.

    2009-01-01

    The present study was undertaken to evaluate the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea for its protective effects on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of gentamicin 100 mg/kg/d for eight days. Effect of concurrent administration of ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea at a dose of 300 mg/kg/d given by oral route was determined using serum creatinine, serum uric acid, blood urea nitrogen and serum urea as indicators of kidney damage. The study groups contained six rats in each group. It was observed that the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea significantly protect rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the groups receiving the leaf and unripe pods extract of Bauhinia purpurea along with gentamicin. The extracts also normalized the gentamicin-induced increase in serum creatinine, serum uric acid and blood urea nitrogen levels. This is also evidenced by the histopathological studies. PMID:20502576

  13. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Tong Zhou

    2017-01-01

    Full Text Available Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT, aspartate transaminase (AST, hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

  14. Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2016-10-01

    Full Text Available Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS. Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

  15. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    International Nuclear Information System (INIS)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2015-01-01

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells

  16. Protective effects of tenuigenin on Staphylococcus aureus-induced pneumonia in mice.

    Science.gov (United States)

    Yu, Bin; Qiao, Jiutao; Shen, Yongbin; Li, Lianyong

    2017-09-01

    Pneumonia is the leading cause of death in infants and young children. Staphylococcus aureus (S.aureus) is one of the most important bacteria that leads to pneumonia. Tenuigenin (TGN), a major active component isolated from the root of the Chinese herb Polygala tenuifolia, has been known to have anti-inflammatory effect. In this study, we aimed to investigate the protective effects of TGN on S.aureus-induced pneumonia in mice. The results showed that TGN significantly attenuated S.aureus-induced lung histopathological changes. TGN also inhibited lung wet/dry (W/D) ratio, and inflammatory cytokines TNF-α and IL-1β production. Furthermore, S.aureus-induced NF-κB activation was significantly inhibited by the treatment of TGN. In conclusion, the results of this study showed that TGN protected against S.aureus-induced pneumonia by inhibiting NF-κB activation. TGN might be a potential agent in the treatment of pneumonia induced by S.aureus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Increasing Optimism Protects Against Pain-Induced Impairment in Task-Shifting Performance.

    Science.gov (United States)

    Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

    2017-04-01

    Persistent pain can lead to difficulties in executive task performance. Three core executive functions that are often postulated are inhibition, updating, and shifting. Optimism, the tendency to expect that good things happen in the future, has been shown to protect against pain-induced performance deterioration in executive function updating. This study tested whether this protective effect of a temporary optimistic state by means of a writing and visualization exercise extended to executive function shifting. A 2 (optimism: optimism vs no optimism) × 2 (pain: pain vs no pain) mixed factorial design was conducted. Participants (N = 61) completed a shifting task once with and once without concurrent painful heat stimulation after an optimism or neutral manipulation. Results showed that shifting performance was impaired when experimental heat pain was applied during task execution, and that optimism counteracted pain-induced deterioration in task-shifting performance. Experimentally-induced heat pain impairs shifting task performance and manipulated optimism or induced optimism counteracted this pain-induced performance deterioration. Identifying psychological factors that may diminish the negative effect of persistent pain on the ability to function in daily life is imperative. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2015-02-20

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  19. Protective effects of escin against indomethacin-induced gastric ulcer in mice.

    Science.gov (United States)

    Wang, Tian; Zhao, Shanshan; Wang, Yucun; Yang, Yujiao; Yao, Le; Chu, Liuxiang; Du, Hanhan; Fu, Fenghua

    2014-12-01

    Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect.

  20. Creatine phosphate disodium salt protects against Dox-induced cardiotoxicity by increasing calumenin.

    Science.gov (United States)

    Wang, Yu; Sun, Ying; Guo, Xin; Fu, Yao; Long, Jie; Wei, Cheng-Xi; Zhao, Ming

    2018-06-01

    Inhibiting endoplasmic reticulum stress (ERS)-induced apoptosis may be a new therapeutic target in cardiovascular diseases. Creatine phosphate disodium salt (CP) has been reported to have cardiovascular protective effect, but its effects on ERS are unknown. The aim of this study was to identify the mechanism by which CP exerts its cardioprotection in doxorubicin (Dox)-induced cardiomyocytes injury. In our study, neonatal rats cardiomyocytes (NRC) was randomly divided into control group, model group, and treatment group. The cell viability and apoptosis were detected. grp78, grp94, and calumenin of the each group were monitored. To investigate the role of calumenin, Dox-induced ERS was compared in control and down-regulated calumenin cardiomyocytes. Our results showed that CP decreased Dox-induced apoptosis and relieved ERS. We found calumenin increased in Dox-induced apoptosis with CP. ERS effector C/EBP homologous protein was down-regulated by CP and it was influenced by calumenin. CP could protect NRC by inhibiting ERS, this mechanisms may be associated with its increasing of calumenin.

  1. Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model

    DEFF Research Database (Denmark)

    Julien, S; Picco, G; Sewell, R

    2009-01-01

    challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed...... by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number...

  2. The protective effect of hypoxia and dithiothreitol on X-ray-induced genetic damage in Arabidopsis

    International Nuclear Information System (INIS)

    Sree Ramulu, K.; Veen, J.H. van der

    1987-01-01

    A study was made on the protective effect of hypoxia and dithiothreitol (DTT) on X-ray-induced ovule sterility and embryonic lethality in Arabidopsis. Both hypoxia and DTT gave a pronounced and additive reduction of radiation-induced genetic damage. The reduction was significantly higher for ovule sterility than for embryonic lethals. It is suggested that non-fertilized ovules contain a higher ratio of strand breaks/other damage than embryonic lethals do, for hypoxia and DTT are known specifically to give a reduction of strand breaks. (Auth.)

  3. ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage.

    Science.gov (United States)

    Sato, Teruki; Sato, Chitose; Kadowaki, Ayumi; Watanabe, Hiroyuki; Ho, Lena; Ishida, Junji; Yamaguchi, Tomokazu; Kimura, Akinori; Fukamizu, Akiyoshi; Penninger, Josef M; Reversade, Bruno; Ito, Hiroshi; Imai, Yumiko; Kuba, Keiji

    2017-06-01

    Elabela/Toddler/Apela (ELA) has been identified as a novel endogenous peptide ligand for APJ/Apelin receptor/Aplnr. ELA plays a crucial role in early cardiac development of zebrafish as well as in maintenance of self-renewal of human embryonic stem cells. Apelin was the first identified APJ ligand, and exerts positive inotropic heart effects and regulates the renin-angiotensin system. The aim of this study was to investigate the biological effects of ELA in the cardiovascular system. Continuous infusion of ELA peptide significantly suppressed pressure overload-induced cardiac hypertrophy, fibrosis and impaired contractility in mice. ELA treatment reduced mRNA expression levels of genes associated with heart failure and fibrosis. The cardioprotective effects of ELA were diminished in APJ knockout mice, indicating that APJ is the key receptor for ELA in the adult heart. Mechanistically, ELA downregulated angiotensin-converting enzyme (ACE) expression in the stressed hearts, whereas it showed little effects on angiotensin-converting enzyme 2 (ACE2) expression, which are distinct from the effects of Apelin. FoxM1 transcription factor, which induces ACE expression in the stressed hearts, was downregulated by ELA but not by Apelin. ELA antagonized angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. The ELA-APJ axis protects from pressure overload-induced heart failure possibly via suppression of ACE expression and pathogenic angiotensin II signalling. The different effects of ELA and Apelin on the expression of ACE and ACE2 implicate fine-tuned mechanisms for a ligand-induced APJ activation and downstream signalling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  4. Outer membrane vesicles of Gallibacterium anatis induce protective immunity in egg-laying hens.

    Science.gov (United States)

    Pors, Susanne E; Pedersen, Ida J; Skjerning, Ragnhild Bager; Thøfner, Ida C N; Persson, Gry; Bojesen, Anders M

    2016-11-15

    Gallibacterium anatis causes infections in the reproductive tract of egg-laying hens and induce increased mortality and decreased egg production. New prophylactic measures are needed in order to improve animal welfare and production efficiency. Bacterial outer membrane vesicles (OMVs) have previously shown promising results in protection against infections and we hypothesized that OMVs could serve as an immunogen to protect egg-laying hens against G. anatis. To investigate the immunogenic potential of G. anatis OMVs, two in vivo studies in egg-laying hens were made. The trials assessedthe degree of protection provided by immunization with G. anatis OMV against challenge and the IgY responses in serum after immunization and challenge, respectively. A total of 64 egg-laying hens were included in the trials. OMVs for immunization were produced and purified from a high-producing G. anatis ΔtolR mutant. Challenge was done with G. anatis 12656-12 and evaluated by scoring lesions and bacterial re-isolation rates from peritoneum. Finally, levels of OMV-specific IgY in sera were assayed by ELISA. Immunization with OMVs decreased the lesions scores significantly, while the bacterial re-isolation remained unchanged. Furthermore, a high OMV-specific IgY response was induced by immunization and subsequent challenge of the hens. The results strongly indicate that immunization with G. anatis OMVs provides significant protection against G. anatis challenge and induces specific antibody responses with high titers of OMV-specific IgY in serum. The results therefore show great promise for OMV based vaccines aiming at providing protecting against G. anatis in egg-laying hens. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Zhigang Zhang

    2014-01-01

    Full Text Available Resveratrol (Rev can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3 is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.

  6. Sirt3 confers protection against acrolein-induced oxidative stress in cochlear nucleus neurons.

    Science.gov (United States)

    Qu, Juan; Wu, Yong-Xiang; Zhang, Ting; Qiu, Yang; Ding, Zhong-Jia; Zha, Ding-Jun

    2018-03-01

    Acrolein is a ubiquitous dietary and environmental pollutant, which can also be generated endogenously during cellular stress. However, the molecular mechanisms underlying acrolein-induced neurotoxicity, especially in ototoxicity conditions, have not been fully determined. In this study, we investigated the mechanisms on acrolein-induced toxicity in primary cultured cochlear nucleus neurons with focus on Sirt3, a mitochondrial deacetylase. We found that acrolein treatment induced neuronal injury and programmed cell death (PCD) in a dose dependent manner in cochlear nucleus neurons, which was accompanied by increased intracellular reactive oxygen species (ROS) generation and lipid peroxidation. Acrolein exposure also significantly reduced the mitochondrial membrane potential (MMP) levels, promoted cytochrome c release and decreased mitochondrial ATP production. In addition, increased ER tracker fluorescence and activation of ER stress factors were observed after acrolein treatment, and the ER stress inhibitors were shown to attenuate acrolein-induced toxicity in cochlear nucleus neurons. The results of western blot and RT-PCR showed that acrolein markedly decreased the expression of Sirt3 at both mRNA and protein levels, and reduced the activity of downstream mitochondrial enzymes. Furthermore, overexpression of Sirt3 by lentivirus transfection partially prevented acrolein-induced neuronal injury in cochlear nucleus neurons. These results demonstrated that acrolein induces mitochondrial dysfunction and ER stress in cochlear nucleus neurons, and Sirt3 acts as an endogenous protective factor in acrolein-induced ototoxicity. Copyright © 2017. Published by Elsevier Ltd.

  7. Protective Effects of Curcumin on Manganese-Induced BV-2 Microglial Cell Death.

    Science.gov (United States)

    Park, Euteum; Chun, Hong Sung

    2017-08-01

    Curcumin, a bioactive component in tumeric, has been shown to exert antioxidant, anti-inflammatory, anticarcinogenic, hepatoprotective, and neuroprotective effects, but the effects of curcumin against manganese (Mn)-mediated neurotoxicity have not been studied. This study examined the protective effects of curcumin on Mn-induced cytotoxicity in BV-2 microglial cells. Curcumin (0.1-10 µM) dose-dependently prevented Mn (250 µM)-induced cell death. Mn-induced mitochondria-related apoptotic characteristics, such as caspase-3 and -9 activation, cytochrome c release, Bax increase, and Bcl-2 decrease, were significantly suppressed by curcumin. In addition, curcumin significantly increased intracellular glutathione (GSH) and moderately potentiated superoxide dismutase (SOD), both which were diminished by Mn treatment. Curcumin pretreatment effectively suppressed Mn-induced upregulation of malondialdehyde (MDA), total reactive oxygen species (ROS). Moreover, curcumin markedly inhibited the Mn-induced mitochondrial membrane potential (MMP) loss. Furthermore, curcumin was able to induce heme oxygenase (HO)-1 expression. Curcumin-mediated inhibition of ROS, down-regulation of caspases, restoration of MMP, and recovery of cell viability were partially reversed by HO-1 inhibitor (SnPP). These results suggest the first evidence that curcumin can prevent Mn-induced microglial cell death through the induction of HO-1 and regulation of oxidative stress, mitochondrial dysfunction, and apoptotic events.

  8. Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage.

    Science.gov (United States)

    Chen, Liming; Liu, Yinghui; Dong, Liangliang; Chu, Xiaoxia

    2015-03-01

    Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p edaravone offers protection from radiation-induced cytogenetic alterations.

  9. Advances in induced resistance by natural compounds: towards new options for woody crop protection

    Directory of Open Access Journals (Sweden)

    Eugenio Llorens

    Full Text Available ABSTRACT: The activation of defensive responses of plants is a promising tool for controlling pests in conventional agriculture. Over the last few years, several compounds have been studied to protect crops from pests, without displaying direct toxicity for pathogenic organisms. These compounds have the ability to induce a priming state on the plants that results in resistance (or tolerance against subsequent infection by a pathogen. In terms of molecular response, induced plant defense involves a broad number of physical and biochemical changes such as callose deposition or phenolic compounds, activation of salicylic and/or jasmonic acid pathways or synthesis of defense-related enzymes. Despite the large number of studies performed to ascertain the physiological and biochemical basis of induced resistance, only a few resistance-activating compounds have been studied as a real alternative to classic means of control and the studies geared towards incorporating induced resistance into disease management programs are relatively rare. The incorporation of natural resistance inducer in pest management programs of woody crops, alone or in combination with classical methods, could be a reliable method for reducing the amount of chemical residues in the environment. In this review, we discuss the current knowledge of induced resistance in woody crops, focusing on the mode of action of compounds authorized for conventional agriculture. We conclude by discussing the environmental and economic advantages of applying resistance inducers to conventional agriculture with special emphasis on natural compounds.

  10. Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions.

    Science.gov (United States)

    Haces, María L; Hernández-Fonseca, Karla; Medina-Campos, Omar N; Montiel, Teresa; Pedraza-Chaverri, José; Massieu, Lourdes

    2008-05-01

    Ketone bodies play a key role in mammalian energy metabolism during the suckling period. Normally ketone bodies' blood concentration during adulthood is very low, although it can rise during starvation, an exogenous infusion or a ketogenic diet. Whenever ketone bodies' levels increase, their oxidation in the brain rises. For this reason they have been used as protective molecules against refractory epilepsy and in experimental models of ischemia and excitotoxicity. The mechanisms underlying the protective effect of these compounds are not completely understood. Here, we studied a possible antioxidant capacity of ketone bodies and whether it contributes to the protection against oxidative damage induced during hypoglycemia. We report for the first time the scavenging capacity of the ketone bodies, acetoacetate (AcAc) and both the physiological and non-physiological isomers of beta-hydroxybutyrate (D- and L-BHB, respectively), for diverse reactive oxygen species (ROS). Hydroxyl radicals (.OH) were effectively scavenged by D- and L-BHB. In addition, the three ketone bodies were able to reduce cell death and ROS production induced by the glycolysis inhibitor, iodoacetate (IOA), while only D-BHB and AcAc prevented neuronal ATP decline. Finally, in an in vivo model of insulin-induced hypoglycemia, the administration of D- or L-BHB, but not of AcAc, was able to prevent the hypoglycemia-induced increase in lipid peroxidation in the rat hippocampus. Our data suggest that the antioxidant capacity contributes to protection of ketone bodies against oxidative damage in in vitro and in vivo models associated with free radical production and energy impairment.

  11. Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice

    Directory of Open Access Journals (Sweden)

    Lin-Hua Wu

    2011-01-01

    Full Text Available This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS-induced inflammatory bowel disease (IBD model of mice. The study employed female C57BL/6 mice (n = 50, and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10: vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg-1 daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO, interleukin (IL-12, IL-10, tumor necrosis factor (TNF-α and interferon (IFN-γ. The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg-1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation.

  12. Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats

    OpenAIRE

    Zaghlool, Sameh S.; Shehata, Basim A.; Abo-Seif, Ali A.; Abd El-Latif, Hekma A.

    2015-01-01

    Background: Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats. Materials and Methods: Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and m...

  13. Protective effects of Bombyx mori, quercetin and benazepril against doxorubicin induced cardiotoxicity and nephrotoxicity

    OpenAIRE

    Abdul S. Nazmi; Shibli J. Ahmad; Krishna K. Pillai; Mohammad Akhtar; Aftab Ahmad; Abul K. Najmi

    2016-01-01

    The present study was conducted with the aim of evaluating the protective effects of Bombyx mori, quercetin and benazepril on doxorubicin (DXR) induced cardiotoxicity and nephrotoxicity in rats. B. mori, quercetin and benazepril were administered for 7 days, and a single intravenous injection of 10 mg/kg body weight of DXR on day five. The animals were sacrificed 48 h after DXR administration. DXR produced a significant elevation in the malondialdehyde (MDA) level and significantly inhibited ...

  14. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats

    OpenAIRE

    Glendenning, Michele L.; Lovekamp-Swan, Tara; Schreihofer, Derek A.

    2008-01-01

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized an...

  15. Interface-Induced Zeeman-Protected Superconductivity in Ultrathin Crystalline Lead Films

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2018-04-01

    Full Text Available Two-dimensional (2D superconducting systems are of great importance for exploring exotic quantum physics. The recent development of fabrication techniques has stimulated studies of high-quality single-crystalline 2D superconductors, where intrinsic properties give rise to unprecedented physical phenomena. Here, we report the observation of Zeeman-type spin-orbit interaction protected superconductivity (Zeeman-protected superconductivity in 4-monolayer (ML to 6-ML crystalline Pb films grown on striped incommensurate Pb layers on Si(111 substrates by molecular beam epitaxy. An anomalously large in-plane critical field far beyond the Pauli limit is detected, which can be attributed to the Zeeman-protected superconductivity due to the in-plane inversion symmetry breaking at the interface. Our work demonstrates that, in superconducting heterostructures, the interface can induce Zeeman-type spin-orbit interactions and modulate the superconductivity.

  16. CLIQ – Coupling-Loss Induced Quench System for Protecting Superconducting Magnets

    CERN Multimedia

    Ravaioli, E; Kirby, G; ten Kate, H H J; Verweij, A P

    2014-01-01

    The recently developed Coupling-Loss-Induced Quench (CLIQ) protection system is a new method for initiating a fast and voluminous transition to the normal state for protecting high energy density superconducting magnets. Upon quench detection, CLIQ is triggered to generate an oscillating current in the magnet coil by means of a capacitive discharge. This in turn introduces a high coupling loss in the superconductor which provokes a quick transition to the normal state of the coil windings. The system is now implemented for the protection of a two meter long superconducting quadrupole magnet and characterized in the CERN magnet test facility. Various CLIQ configurations with different current injection points are tested and the results compared to similar transients lately measured with a not optimized configuration. Test results convincingly show that the newly tested design allows for a more global quench initiation and thus a faster discharge of the magnet energy. Moreover, the performance of CLIQ for reduc...

  17. Interface-Induced Zeeman-Protected Superconductivity in Ultrathin Crystalline Lead Films

    Science.gov (United States)

    Liu, Yi; Wang, Ziqiao; Zhang, Xuefeng; Liu, Chaofei; Liu, Yongjie; Zhou, Zhimou; Wang, Junfeng; Wang, Qingyan; Liu, Yanzhao; Xi, Chuanying; Tian, Mingliang; Liu, Haiwen; Feng, Ji; Xie, X. C.; Wang, Jian

    2018-04-01

    Two-dimensional (2D) superconducting systems are of great importance for exploring exotic quantum physics. The recent development of fabrication techniques has stimulated studies of high-quality single-crystalline 2D superconductors, where intrinsic properties give rise to unprecedented physical phenomena. Here, we report the observation of Zeeman-type spin-orbit interaction protected superconductivity (Zeeman-protected superconductivity) in 4-monolayer (ML) to 6-ML crystalline Pb films grown on striped incommensurate Pb layers on Si(111) substrates by molecular beam epitaxy. An anomalously large in-plane critical field far beyond the Pauli limit is detected, which can be attributed to the Zeeman-protected superconductivity due to the in-plane inversion symmetry breaking at the interface. Our work demonstrates that, in superconducting heterostructures, the interface can induce Zeeman-type spin-orbit interactions and modulate the superconductivity.

  18. Nanodiamonds protect skin from ultraviolet B-induced damage in mice.

    Science.gov (United States)

    Wu, Meng-Si; Sun, Der-Shan; Lin, Yu-Chung; Cheng, Chia-Liang; Hung, Shih-Che; Chen, Po-Kong; Yang, Jen-Hung; Chang, Hsin-Hou

    2015-05-07

    Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide and zinc oxide offer effective protection and enhance cosmetic appearance but entail health concerns regarding their photocatalytic activity, which generates reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among the UV wavelengths in sunlight, UVB irradiation primarily threatens human health. The efficacy and safety of NDs in UVB protection were evaluated using cell cultures and mouse models. We determined that 2 mg/cm(2) of NDs efficiently reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND-shielding significantly protected the aforementioned pathogenic alterations in both cell cultures and mouse models. NDs are feasible and safe materials for preventing UVB-induced skin damage.

  19. Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

    Science.gov (United States)

    Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

  20. Protective effects of vitamin C against gamma-ray induced wholly damage and genetic damage

    International Nuclear Information System (INIS)

    Fu Chunling; Jiang Weiwei; Zhang Ping; Chen Xiang; Zhu Shengtao

    2000-01-01

    Objective: Protective effects of supplemental vitamin C against 60 Co-gamma-ray induced wholly damage and genetic damage was investigated in mice. Method: Mice were divided into normal control group, irradiation control group and vitamin C experimental group 1,2,3 (which were orally given vitamin C 15, 30, 45 mg/kg.bw for 10 successive days respectively prior to gamma-ray irradiation). Micronuclei in the bone marrow polychromatophilic erythrocytes in each group of mice were examined and the 30 day survival rate of mice following whole-body 5.0 Gy γ irradiation were also determined. Results: Supplemental vitamin C prior to gamma-rays irradiation can significantly decrease bone marrow PECMN rate of mice and increase 30 day survival rate and prolong average survival time. The protection factor is 2.09. Conclusion: Vitamin C has potent protective effects against gamma irradiation induced damage in mice. In certain dose range, vitamin C can absolutely suppress the gamma-rays induced genetic damage in vivo

  1. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Chuanyu Wei

    Full Text Available Pulmonary hypertension (PH is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC dysfunction and pulmonary arterial smooth muscle cell (PASMC proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4 is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.

  2. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    Directory of Open Access Journals (Sweden)

    Nur Shafika Mohd Sairazi

    2015-01-01

    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  3. Total Leishmania antigens with Poly(I:C) induce Th1 protective response.

    Science.gov (United States)

    Sanchez, M V; Eliçabe, R J; Di Genaro, M S; Germanó, M J; Gea, S; García Bustos, M F; Salomón, M C; Scodeller, E A; Cargnelutti, D E

    2017-11-01

    Our proposal was to develop a vaccine based on total Leishmania antigens (TLA) adjuvanted with polyinosinic-polycytidylic acid [Poly(I:C)] able to induce a Th1 response which can provide protection against Leishmania infection. Mice were vaccinated with two doses of TLA-Poly(I:C) administered by subcutaneous route at 3-week interval. Humoral and cellular immune responses induced by the immunization were measured. The protective efficacy of the vaccine was evaluated by challenging mice with infective promastigotes of Leishmania (Leishmania) amazonensis into the footpad. Mice vaccinated with TLA-Poly(I:C) showed a high anti-Leishmania IgG titre, as well as increased IgG1 and IgG2a subclass titres compared with mice vaccinated with the TLA alone. The high IgG2a indicated a Th1 bias response induced by the TLA-Poly(I:C) immunization. Accordingly, the cellular immune response elicited by the formulation was characterized by an increased production of IFN-γ and no significant production of IL-4. The TLA-Poly(I:C) immunization elicited good protection, which was associated with decreased footpad swelling, a lower parasite load and a reduced histopathological alteration in the footpad. Our findings demonstrate a promising vaccine against cutaneous leishmaniasis that is relatively economic and easy to develop and which should be taken into account for preventing leishmaniasis in developing countries. © 2017 John Wiley & Sons Ltd.

  4. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Xian-lin Wu

    2015-01-01

    Full Text Available Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP. The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS and multiple organ dysfunction syndromes (MODS to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

  5. Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

    International Nuclear Information System (INIS)

    Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

    2010-01-01

    Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

  6. Gastrointestinal protective effect of dietary spices during ethanol-induced oxidant stress in experimental rats.

    Science.gov (United States)

    Prakash, Usha N S; Srinivasan, Krishnapura

    2010-04-01

    Spices are traditionally known to have digestive stimulant action and to cure digestive disorders. In this study, the protective effect of dietary spices with respect to activities of antioxidant enzymes in gastric and intestinal mucosa was examined. Groups of Wistar rats were fed for 8 weeks with diets containing black pepper (0.5%), piperine (0.02%), red pepper (3.0%), capsaicin (0.01%), and ginger (0.05%). All these spices significantly enhanced the activities of antioxidant enzymes--superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase--in both gastric and intestinal mucosa, suggesting a gastrointestinal protective role for these spices. In a separate study, these dietary spices were found to alleviate the diminished activities of antioxidant enzymes in gastric and intestinal mucosa under conditions of ethanol-induced oxidative stress. The gastroprotective effect of the spices was also reflected in their positive effect on mucosal glycoproteins, thereby lowering mucosal injury. The amelioration of the ethanol-induced decrease in the activities of antioxidant enzymes in gastric and intestinal mucosa by dietary spices suggests their beneficial gastrointestinal protective role. This is the first report on the gastrointestinal protective potential of dietary spices.

  7. Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.

    Science.gov (United States)

    Kim, Yeu-Chun; Lee, Su-Hwa; Choi, Won-Hyung; Choi, Hyo-Jick; Goo, Tae-Won; Lee, Ju-Hie; Quan, Fu-Shi

    2016-12-01

    A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.

  8. PARP inhibitors protect against sex- and AAG-dependent alkylation-induced neural degeneration.

    Science.gov (United States)

    Allocca, Mariacarmela; Corrigan, Joshua J; Fake, Kimberly R; Calvo, Jennifer A; Samson, Leona D

    2017-09-15

    Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type and Aag -transgenic ( AagTg ) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1). Here, we tested whether PARP inhibitors can also prevent alkylation-induced retinal and cerebellar degeneration in male and female WT and AagTg mice. Importantly, we found that WT mice display sex-dependent alkylation-induced retinal damage (but not cerebellar damage), with WT males being more sensitive than females. Accordingly, estradiol treatment protects males against alkylation-induced retinal degeneration. In AagTg male and female mice, the alkylation-induced tissue damage in both the retina and cerebellum is exacerbated and the sex difference in the retina is abolished. PARP inhibitors, much like Parp1 gene deletion, protect against alkylation-induced AAG-dependent neuronal degeneration in WT and AagTg mice, regardless of the gender, but their efficacy in preventing alkylation-induced neuronal degeneration depends on PARP inhibitor characteristics and doses. The recent surge in the use of PARP inhibitors in combination with cancer chemotherapeutic alkylating agents might represent a powerful tool for obtaining increased therapeutic efficacy while avoiding the collateral effects of alkylating agents in healthy tissues.

  9. Heart protection by combination therapy with esmolol and milrinone at late-ischemia and early reperfusion.

    Science.gov (United States)

    Huang, Ming-He; Wu, Yewen; Nguyen, Vincent; Rastogi, Saurabh; McConnell, Bradley K; Wijaya, Cori; Uretsky, Barry F; Poh, Kian-Keong; Tan, Huay-Cheem; Fujise, Kenichi

    2011-06-01

    The present study determined whether late-ischemia/early reperfusion therapy with the β(1)-adrenergic receptor (AR) blocker esmolol and phosphodiesterase III inhibitor milrinone reduced left ventricular (LV) myocardial infarct size (IS). In an ischemia/reperfusion rat model (30-min ischemia/4-hr reperfusion), esmolol, milrinone or esmolol + milrinone were intravenous (IV) infused over 10 min (from the last 5 min of ischemia to the first 5 min of reperfusion). LV-IS were 48.9 ± 8.9%, 41.5 ± 5.4%, 25.8 ± 7.7% and 16.8 ± 7.3% for saline, esmolol, milrinone, and esmolol + milrinone, respectively (n = 12/group). Esmolol + milrinone further reduced LV-IS compared with esmolol or milrinone alone (p milrinone was eliminated in the presence of protein kinase A-(PKA)-inhibitor (Rp-cAMPS) or Akt-inhibitor (AKT 1/2 kinase inhibitor). In mixed rat ventricular cardiomyocyte cultures, intra-ischemic application of esmolol, milrinone or esmolol + milrinone reduced myocyte death rates by 5.5%, 13.3%, and 16.8%, respectively, compared with saline (p milrinone was abrogated in the presence of PKA-inhibitor or Akt-inhibitor. Esmolol, milrinone or esmolol + milrinone increased myocardial PKA activity by 22%, 28% and 59%, respectively, compared with saline (n = 6, p milrinone or esmolol + milrinone, there were 1.7-, 2.7-, and 6-fold increase in tissue pAkt levels, respectively. This esmolol + milrinone induced pAkt activation was abolished in the presence of PKA inhibitor. Esmolol, milrinone and esmolol + milrinone reduced myocyte apoptosis rates by 22%, 37% and 60%, respectively, compared with saline (p milrinone additively reduces LV-IS associated with robust activation of myocardial PKA and subsequent Akt-antiapoptotic pathway.

  10. Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis.

    Science.gov (United States)

    Vordermeier, H Martin; Villarreal-Ramos, Bernardo; Cockle, Paul J; McAulay, Martin; Rhodes, Shelley G; Thacker, Tyler; Gilbert, Sarah C; McShane, Helen; Hill, Adrian V S; Xing, Zhou; Hewinson, R Glyn

    2009-08-01

    Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development.

  11. Bifenthrin-induced oxidative stress in human erythrocytes in vitro and protective effect of selected flavonols.

    Science.gov (United States)

    Sadowska-Woda, Izabela; Popowicz, Diana; Karowicz-Bilińska, Agata

    2010-03-01

    Bifenthrin is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activity used to control wide range of insect pests in a variety of applications. This investigation was designed to examine (1) bifenthrin as an inducer of oxidative stress in human erythrocytes in vitro through effects on catalase (CAT) and superoxide dismutase (SOD) activities, and (2) the role of the flavonoids quercetin (Q, 40 and 80microM) and rutin (R, 80microM) in alleviating the effects of bifenthrin. Erythrocytes were divided into portions. The first portion was incubated for 4h at 37 degrees C with different concentrations (0, 42.2, 211, 1055ppm) of bifenthrin. The other portions were preincubated with Q or R for 30min, followed incubation with bifenthrin for 4h. The influence of solvent (ethanol) was also checked on the parameters studied. Malondialdehyde (MDA) concentrations, CAT and SOD activities were measured in all treatment portions of erythrocytes. Our results demonstrated that bifenthrin-induced oxidative stress causes enhanced lipid peroxidation and decreased antioxidative enzyme activities in human peripheral blood. R pretreated erythrocytes were protected against the increase of MDA induced by bifenthrin. Q (80microM) and R pretreated erythrocytes were protected against the inhibition of CAT activity induced by bifenthrin. The protective action against the inhibition of SOD activity of Q was greater than that of R at the same concentration. These results suggest that Q and R may play a role in reducing bifenthrin-induced oxidative stress in vitro. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  12. Protective effect of bicyclol on tetracycline-induced fatty liver in mice

    International Nuclear Information System (INIS)

    Yu, Hong-Yan; Wang, Bao-Lian; Zhao, Jing; Yao, Xiao-Min; Gu, Yu; Li, Yan

    2009-01-01

    Peroxisome proliferators-activated receptor α (PPARα) and oxidative stress are two important pathological factors in non-alcoholic fatty liver disease (NAFLD). Tetracycline-induced fatty liver was partly due to the disturbance of mitochondrial fatty acids β-oxidation regulated by PPARα. Bicyclol was found to protect against high fat diet-induced fatty liver through modulating PPARα and clearing reactive oxygen species (ROS). The present study was performed to further investigate the effect of bicyclol on tetracycline-induced fatty liver and related mechanism in mice. Bicyclol (75, 150, 300 mg/kg) was given orally three times in two consecutive days. Tetracycline (200 mg/kg) was injected intraperitoneally 1 h after the last administration of bicyclol. Oxidative stress, mitochondrial function, PPARα and its target genes were evaluated by biochemical and RT-PCR analysis. The activity of CYP4A was assessed by liquid chromatography/mass spectrometry (LC/MS) method. Bicyclol significantly protected against tetracycline-induced fatty liver by reducing the accumulation of hepatic lipids and elevation of serum aminotransferase. In addition, bicyclol remarkably alleviated the over-production of thiobarbituric acid-reactive substance. The reduced activity of mitochondrial respiratory chain (MRC) complexes I and IV and mitochondrial permeability transition (MPT) were also improved by bicyclol. Furthermore, bicyclol inhibited the decrease of PPARα expression and its target genes, including long-chain acyl CoA dehydrogenase (LCAD), acetyl CoA oxidase (AOX) and CYP4A at mRNA and enzyme activity level. Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARα pathway and ameliorating mitochondrial function.

  13. Radiotherapy-induced Early ECG Changes and Their Comparison with Echocardiography in Patients with Early-stage Breast Cancer.

    Science.gov (United States)

    Tuohinen, Suvi Sirkku; Keski-Pukkila, Konsta; Skyttä, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka; Nikus, Kjell

    2018-04-01

    Early electrocardiogram (ECG) changes after breast cancer radiotherapy (RT) have been reported, but their characteristics and associated factors are largely unknown. This study aimed to explore early RT-induced ECG changes and to compare them with echocardiography changes. Sixty eligible patients with chemotherapy-naïve left-sided and 20 with right-sided breast cancer were evaluated with echocardiography, blood samples and ECG before and after RT. RT-induced ECG changes in the anterior leads. T-Wave changes were most frequent. T-Wave decline was associated independently with patient age (β=-0.245, p=0.005), mean heart radiation dose (β=1.252, p=0.001) and global systolic strain rate change (β=7.943, p=0.002). T-Wave inversion was associated independently with mean heart radiation dose (β=0.143, pECG changes were prevalent and associated with functional and structural changes in echocardiography. ECG could be used for post-RT cardiac screening. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Phenylbutyric acid protects against carbon tetrachloride-induced hepatic fibrogenesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian-Qing [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Tao, Li [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Zhi-Hui; Liu, Xiao-Qian [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Xu, Yuan-Bao [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Hua [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Li, Jun, E-mail: lijun@ahmu.edu.cn [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Xu, De-Xiang, E-mail: xudex@126.com [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China)

    2013-01-15

    hepatic NF-κB activation and ERK and JNK phosphorylation. ► PBA effectively protects against CCl{sub 4}-induced HSC activation and hepatic fibrosis. ► ER stress is involved in CCl{sub 4}-induced hepatic inflammation and fibrogenesis.

  15. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    Science.gov (United States)

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

  16. Protective Effect of Piper aduncum Capsule on DMBA-induced Breast Cancer in Rats.

    Science.gov (United States)

    Arroyo-Acevedo, J; Chávez-Asmat, R J; Anampa-Guzmán, A; Donaires, R; Ráez-Gonzáles, José

    2015-01-01

    The possible protective effect of Piper aduncum capsule on DMBA (dimethylbenz[α]anthracene)-induced breast cancer in rats was assessed by monitoring the tumor and lung metastases incidence and recording hematological and biochemical parameters and frequency of micronuclei. Mammary carcinogenesis was induced in 36 female Holtzman rats by providing a single subcutaneous injection of DMBA. Oral administration of P. aduncum capsule lowered adenocarcinoma and lymph node metastases incidence. Pulmonary metastasis was significantly lowered (P < 0.05). Hematological indicators showed that the triglyceride level was significantly lowered (P < 0.01) and high-density lipoprotein (HDL) level was significantly increased (P < 0.01). Also, P. aduncum capsule significantly lowered the C reactive protein (CRP) level (P < 0.01) and malondialdehyde level (P < 0.05). There was a significant decrease in the frequency of DMBA-induced micronucleated polychromatic erythrocyte (P < 0.01). Considering the antitumorigenic, hypolipidemic, anti-inflammatory, antioxidant, and antigenotoxic properties of P. aduncum capsule, we conclude that it has a protective effect on DMBA-induced breast cancer in rats.

  17. Dexmedetomidine May Produce Extra Protective Effects on Sepsis-induced Diaphragm Injury

    Directory of Open Access Journals (Sweden)

    Jin Wu

    2015-01-01

    Full Text Available Objective: The objective was to evaluate the protective effects of dexmedetomidine (DEX, a selective agonist of α2-adrenergic receptor, on sepsis-induced diaphragm injury and the underlying molecular mechanisms. Data Sources: The data used in this review were mainly from PubMed articles published in English from 1990 to 2015. Study Selection: Clinical or basic research articles were selected mainly according to their level of relevance to this topic. Results: Sepsis could induce severe diaphragm dysfunction and exacerbate respiratory weakness. The mechanism of sepsis-induced diaphragm injury includes the increased inflammatory cytokines and excessive oxidative stress and superfluous production of nitric oxide (NO. DEX can reduce inflammatory cytokines, inhibit nuclear factor-kappaB signaling pathways, suppress the activation of caspase-3, furthermore decrease oxidative stress and inhibit NO synthase. On the basis of these mechanisms, DEX may result in a shorter period of mechanical ventilation in septic patients in clinical practice. Conclusions: Based on this current available evidence, DEX may produce extra protective effects on sepsis-induced diaphragm injury. Further direct evidence and more specific studies are still required to confirm these beneficial effects.

  18. Protective Effect of Vitamins E and C on Endosulfan-Induced Reproductive Toxicity in Male Rats

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    Hussain Kargar

    2012-09-01

    Full Text Available Background: The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats.Methods: Fifty adult male Sprague–Dawley rats were randomly divided into five groups (n=10 each. The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day, vitamin E (200 mg/kg/day, or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH, plasma testosterone and malondialdehyde (MDA levels in the testis were determined. Results: Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan.Conclusion: The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

  19. Protective effect of vitamins e and C on endosulfan-induced reproductive toxicity in male rats.

    Science.gov (United States)

    Takhshid, Mohammad Ali; Tavasuli, Ali Reza; Heidary, Yazdan; Keshavarz, Mojtaba; Kargar, Hussain

    2012-09-01

    The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats. Fifty adult male Sprague-Dawley rats were randomly divided into five groups (n=10 each). The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200 mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma testosterone and malondialdehyde (MDA) levels in the testis were determined. Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP) and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan. The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

  20. Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity

    International Nuclear Information System (INIS)

    Oliveira, Paulo J.; Bjork, James A.; Santos, Maria S.; Leino, Richard L.; Froberg, M. Kent; Moreno, Antonio J.; Wallace, Kendall B.

    2004-01-01

    The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a β-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its β-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a β-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its β-adrenergic receptor antagonism

  1. Resveratrol confers protection against rotenone-induced neurotoxicity by modulating myeloperoxidase levels in glial cells.

    Directory of Open Access Journals (Sweden)

    Chi Young Chang

    Full Text Available Myeloperoxidase (MPO functions as a key molecular component of the host defense system against diverse pathogens. We have previously reported that increased MPO levels and activity is a distinguishing feature of rotenone-exposed glial cells, and that either overactivation or deficiency of MPO leads to pathological conditions in the brain. Here, we provide that modulation of MPO levels in glia by resveratrol confers protective effects on rotenone-induced neurotoxicity. We show that resveratrol significantly reduced MPO levels but did not trigger abnormal nitric oxide (NO production in microglia and astrocytes. Resveratrol-induced down-regulation of MPO, in the absence of an associated overproduction of NO, markedly attenuated rotenone-triggered inflammatory responses including phagocytic activity and reactive oxygen species production in primary microglia and astrocytes. In addition, impaired responses of primary mixed glia from Mpo (-/- mice to rotenone were relieved by treatment with resveratrol. We further show that rotenone-induced neuronal injury, particularly dopaminergic cell death, was attenuated by resveratrol in neuron-glia co-cultures, but not in neurons cultured alone. Similar regulatory effects of resveratrol on MPO levels were observed in microglia treated with MPP(+, another Parkinson's disease-linked neurotoxin, supporting the beneficial effects of resveratrol on the brain. Collectively, our findings provide that resveratrol influences glial responses to rotenone by regulating both MPO and NO, and thus protects against rotenone-induced neuronal injury.

  2. Protective effect of mild endoplasmic reticulum stress on radiation-induced bystander effects in hepatocyte cells

    Science.gov (United States)

    Xie, Yuexia; Ye, Shuang; Zhang, Jianghong; He, Mingyuan; Dong, Chen; Tu, Wenzhi; Liu, Peifeng; Shao, Chunlin

    2016-01-01

    Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the defense and self-protective mechanisms of bystander normal cells are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 cells under either normoxia or hypoxia, where the ratio of the yield of bystander MN induction to the yield of radiation-induced MN formation under hypoxia was much higher than that of normoxia. Nonetheless, thapsigargin induced endoplasmic reticulum (ER) stress and dramatically suppressed this bystander response manifested as the decrease of MN and apoptosis inductions. Meanwhile, the interference of BiP gene, a major ER chaperone, amplified the detrimental RIBE. More precisely, thapsigargin provoked ER sensor of PERK to initiate an instantaneous and moderate ER stress thus defensed the hazard form RIBE, while BiP depletion lead to persistently destroyed homeostasis of ER and exacerbated cell injury. These findings provide new insights that the mild ER stress through BiP-PERK-p-eIF2α signaling pathway has a profound role in protecting cellular damage from RIBE and hence may decrease the potential secondary cancer risk after cancer radiotherapy. PMID:27958308

  3. Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1.

    Science.gov (United States)

    Yang, Wei; Kang, Xiaomin; Qin, Na; Li, Feng; Jin, Xinxin; Ma, Zhengmin; Qian, Zhuang; Wu, Shufang

    2017-10-01

    Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively. Dex treatment induced the loss of the extracellular matrix, NAD + /NADH ratio and NADPH concentration in chondrocytes. Melatonin alone have no effect on the quantity of proteoglycans and collagen type IIa1, however, the pretreatment of melatonin reversed the negative effects induced by Dex. Meanwhile, the significant decrease in NAD + /NADH ratio and NADPH concentration in Dex group were up-regulated by pretreatment of melatonin. Furthermore, it was revealed that inhibition of SIRT1 blocked the protective effects of melatonin. The enhancement of NAD + -dependent SIRT1 activity contributes to the chondroprotecfive effects of melatonin, which has a great benefit to prevent dexamethasone-induced chondrocytes impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

    International Nuclear Information System (INIS)

    Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

    2009-01-01

    Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion ( TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

  5. The essential oil of Artemisia capillaris protects against CCl4-induced liver injury in vivo

    Directory of Open Access Journals (Sweden)

    Qinghan Gao

    Full Text Available Abstract To study the hepatoprotective effect of the essential oil of Artemisia capillaris Thunb., Asteraceae, on CCl4-induced liver injury in mice, the levels of serum aspartate aminotransferase and alanine aminotransferase, hepatic levels of reduced glutathione, activity of glutathione peroxidase, and the activities of superoxide dismutase and malondialdehyde were assayed. Administration of the essential oil of A. capillaris at 100 and 50 mg/kg to mice prior to CCl4 injection was shown to confer stronger in vivo protective effects and could observably antagonize the CCl4-induced increase in the serum alanine aminotransferase and aspartate aminotransferase activities and malondialdehyde levels as well as prevent CCl4-induced decrease in the antioxidant superoxide dismutase activity, glutathione level and glutathione peroxidase activity (p < 0.01. The oil mainly contained β-citronellol, 1,8-cineole, camphor, linalool, α-pinene, β-pinene, thymol and myrcene. This finding demonstrates that the essential oil of A. capillaris can protect hepatic function against CCl4-induced liver injury in mice.

  6. Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism.

    Science.gov (United States)

    Singh, Shamsher; Jamwal, Sumit; Kumar, Puneet

    2015-08-01

    3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington's disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-α and IL-1β level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP-induced behavioral and molecular alteration.

  7. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

    Directory of Open Access Journals (Sweden)

    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  8. Glucagon receptor knockout mice are protected against acute olanzapine-induced hyperglycemia.

    Science.gov (United States)

    Castellani, Laura N; Peppler, Willem T; Sutton, Charles D; Whitfield, Jamie; Charron, Maureen J; Wright, David C

    2017-08-01

    To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr -/- ) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined. Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr -/- mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr -/- mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr -/- mice. Gcgr -/- mice are protected against olanzapine-induced increases in blood glucose. This is likely a result of reductions in liver glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein content. Our findings highlight the central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Protection of vanillin derivative VND3207 on plasmid DNA damage induced by different LET ionizing radiation

    International Nuclear Information System (INIS)

    Xu Huihui; Wang Li; Sui Li; Guan Hua; Wang Yu; Liu Xiaodan; Zhang Shimeng; Xu Qinzhi; Wang Xiao; Zhou Pingkun

    2011-01-01

    Objective: To evaluate the radioprotective effect of vanillin derivative VND3207 on DNA damage induced by different LET ionizing radiation. Methods: The plasmid DNA in liquid was irradiated by 60 Co γ-rays, proton or 7 Li heavy ion with or without VND3207. The conformation changes of plasmid DNA were assessed by agarose gel electrophoresis and the quantification was done using gel imaging system. Results: The DNA damage induced by proton and 7 Li heavy ion was much more serious as compared with that by 60 Co γ-rays, and the vanillin derivative VND3207 could efficiently decrease the DNA damage induced by all three types of irradiation sources, which was expressed as a significantly reduced ratio of open circular form (OC) of plasmid DNA. The radioprotective effect of VND3207 increased with the increasing of drug concentration. The protective efficiencies of 200 μmol/L VND3207 were 85.3% (t =3.70, P=0.033), 73.3% (t=10.58, P=0.017) and 80.4% (t=8.57, P=0.008) on DNA damage induction by 50 Gy of γ-rays, proton and 7 Li heavy ion, respectively. It seemed that the radioprotection of VND3207 was more effective on DNA damage induced by high LET heavy ion than that by proton. Conclusions: VND3207 has a protective effect against the genotoxicity of different LET ionizing radiation, especially for γ-rays and 7 Li heavy ion. (authors)

  10. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

    Science.gov (United States)

    Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

    2018-02-05

    Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

  11. Protective effect of U74500A on phorbol myristate acetate-induced acute lung injury.

    Science.gov (United States)

    Chu, Shi-Jye; Chang, Deh-Ming; Wang, David; Lin, Hen-I; Lin, Shih-Hua; Hsu, Kang

    2004-08-01

    1. The present study was designed to determine whether U74500A could ameliorate acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in our rat isolated lung model compared with any amelioration induced by dimethylthiourea (DMTU), superoxide dismutase (SOD) and catalase. 2. Acute lung injury was induced successfully by PMA during 60 min of observation. At 2 microg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/bodyweight ratio, pulmonary arterial pressure and protein concentration of the bronchoalveolar lavage fluid. 3. Pretreatment with 1.5 mg/kg U74500A significantly attenuated ALI; there was no significant increase in any parameters measured, except for pulmonary arterial pressure. The protective effect of U74500A was approximately the same as that of 600 mg/kg DMTU. However, 6000 U/kg SOD, 50,000 U/kg catalase and 6000 U/kg SOD + 50,000 U/kg catalase had no protective effect. 4. These experimental data suggest that U74500A significantly ameliorates ALI induced by PMA in rats.

  12. The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity.

    Science.gov (United States)

    Dkhil, Mohamed A; Al-Quraishy, Saleh; Diab, Marwa M S; Othman, Mohamed S; Aref, Ahmed M; Abdel Moneim, Ahmed E

    2014-12-01

    This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5 mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200 mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. A brain-targeted ampakine compound protects against opioid-induced respiratory depression.

    Science.gov (United States)

    Dai, Wei; Xiao, Dian; Gao, Xiang; Zhou, Xin-Bo; Fang, Tong-Yu; Yong, Zheng; Su, Rui-Bin

    2017-08-15

    The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression. XD-8-17C was intravenously administered before or after TH-030418. The effect of XD-8-17C on opioid-induced respiratory depression was evaluated in terms of the opioid-induced acute death rate, arterial blood gas analysis and pulmonary function tests. In addition, the hot-plate test was conducted to investigate whether XD-8-17C influenced opioid-induced analgesia. Pre-treatment with XD-8-17C significantly reduced opioid-induced acute death, and increased the median lethal dose of TH-030418 by 4.7-fold. Blood gas analysis and pulmonary function tests demonstrated that post-treatment with XD-8-17C alleviated respiratory depression, as indicated by restoration of arterial blood gas (pO 2 , sO 2 , cK + ) and lung function parameters (respiratory frequency, minute ventilation) to the normal range. The hot-plate test showed that XD-8-17C had no impact on the antinociceptive efficacy of morphine. The ability of XD-8-17C to reverse opioid-induced respiratory depression has the potential to increase the safety and convenience of opioid treatment. These findings contribute to the discovery of novel therapeutic agents that protect against opioid-induced respiratory depression without loss of analgesia. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses.

    Science.gov (United States)

    Pouyanfard, Somayeh; Spagnoli, Gloria; Bulli, Lorenzo; Balz, Kathrin; Yang, Fan; Odenwald, Caroline; Seitz, Hanna; Mariz, Filipe C; Bolchi, Angelo; Ottonello, Simone; Müller, Martin

    2018-02-15

    The amino terminus of the human papillomavirus (HPV) minor capsid protein L2 contains a major cross-neutralization epitope which provides the basis for the development of a broadly protecting HPV vaccine. A wide range of protection against different HPV types would eliminate one of the major drawbacks of the commercial, L1-based prophylactic vaccines. Previously, we have reported that insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin protein generates a potent antigen inducing comprehensive protection against different animal and human papillomaviruses. We also reported, however, that although protection is broad, some oncogenic HPV types escape the neutralizing antibody response, if L2 epitopes from single HPV types are used as immunogen. We were able to compensate for this by applying a mix of thioredoxin proteins carrying L2 epitopes from HPV16, -31, and -51. As the development of a cost-efficient HPV prophylactic vaccines is one of our objectives, this approach is not feasible as it requires the development of multiple good manufacturing production processes in combination with a complex vaccine formulation. Here, we report the development of a thermostable thioredoxin-based single-peptide vaccine carrying an L2 polytope of up to 11 different HPV types. The L2 polytope antigens have excellent abilities in respect to broadness of protection and robustness of induced immune responses. To further increase immunogenicity, we fused the thioredoxin L2 polytope antigen with a heptamerization domain. In the final vaccine design, we achieve protective responses against all 14 oncogenic HPV types that we have analyzed plus the low-risk HPVs 6 and 11 and a number of cutaneous HPVs. IMPORTANCE Infections by a large number of human papillomaviruses lead to malignant and nonmalignant disease. Current commercial vaccines based on virus-like particles (VLPs) effectively protect against some HPV types but fail to do so for most others. Further, only

  15. Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model.

    Science.gov (United States)

    Ermler, Megan E; Kirkpatrick, Ericka; Sun, Weina; Hai, Rong; Amanat, Fatima; Chromikova, Veronika; Palese, Peter; Krammer, Florian

    2017-06-15

    Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed. Copyright © 2017 American Society for Microbiology.

  16. Protection from radiation-induced damage to spermatogenesis by hormone treatment

    International Nuclear Information System (INIS)

    Kurdoglu, B.; Wilson, G.; Parchuri, N.; Ye, W.; Meistrich, M.L.

    1994-01-01

    Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism. 32 refs., 3 figs

  17. Radiation induced early delayed changes in mice brain: a 1h MRS and behavioral evaluation study

    International Nuclear Information System (INIS)

    Gupta, Mamta; Rana, Poonam; Haridas, Seenu; Manda, Kailash; Hemanth Kumar, B.S.; Khushu, Subash

    2014-01-01

    Radiation induced CNS injury can be classified as acute, early delayed and late delayed. Most of the studies suggest that acute injury is reversible whereas early delayed and late delayed injury is irreversible leading to metabolic and cognitive impairment. Extensive research has been carried out on cranial radiation induced early and late delayed changes, there are no reports on whole body radiation induced early and delayed changes. The present study was designed to observe early delayed effects of radiation during whole body radiation exposure. A total of 20 C57 male mice were divided in two groups of 10 animals each. One group was exposed to a dose of 5 Gy whole body radiation through Tele 60 Co irradiation facility with source operating at 2.496 Gy/min, while other group served as sham irradiated control. Behavioral and MR spectroscopy was carried out 3 months post irradiation. Behavioral parameters such as locomotor activity and working memory were evaluated first then followed by MR spectroscopy at 7T animal MRI system. For MRS, voxel was localised in the cortex-hippocampus region of mouse brain. MR spectra were acquired using PRESS sequence, FID was processed using LC model for quantitation. The data showed impaired cognitive functions and altered metabolite levels during early delayed phase of whole body radiation induced injury. In behavioural experiments, there was a significant impairment in the cognitive as well as exploratory functions at 3 months post irradiation in irradiated group as compared to controls. MRS results explained changes in mI, glutamine and glx levels in irradiated animals compared to controls. Altered mI level has been found to be associated with reduced cognitive abilities in many brain disorders including MCI and Alzheimer's disease. The findings of this study suggest that whole body radiation exposure may have long lasting effect on the cognitive performance. (author)

  18. Protective Effect of Curcumin on γ - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

    International Nuclear Information System (INIS)

    AlSuhaibani, E.S

    2008-01-01

    The present work is aimed at evaluating the radioprotective effect of curcumin on γ radiation induced genetic toxicity. The DNA damage was analyzed by the frequencies of chromosome aberrations assay. Human lymphocytes were treated in vitro with 5.0 γg/ml of curcumin for 30 min at 37 degree C then exposed to 1, 2 and 4 Gy gamma-radiation. The lymphocytes which were pre-treated with curcumin exhibited a significant decrease in the frequency of chromosome aberration at 1 and 2 Gy radiation-induced chromosome damage as compared with the irradiated cells which did not receive the curcumin pretreatment. Thus, pretreatment with curcumin gives protection to lymphocytes against γ-radiation induced chromosome aberration at certain doses. (author)

  19. Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA

    International Nuclear Information System (INIS)

    Ley, R.D.

    1997-01-01

    Solar ultraviolet radiation (UVR) induces a number of pathologic conditions of mammalian skin including erythema, oedema, hyperplasia, sunburn cell formation and skin cancer. Consequently, UVR-induced DNA damage has been implicated as one of the photochemical events that results in the formation of these pathological changes. The ability of sunscreens to protect against UVR-induced DNA damage has not been well characterized especially with UVA (320-400 nm) wavelengths and UVA absorbers. In this paper we present results of a study aimed at determining the efficacy of two sunscreens at preventing the induction of pyrmidine dimers in basal cell DNA of mice exposed to solar-simulated UVR (SSUV) wavelengths (290-400 nm) or to UVA (320-400 nm). (author)

  20. Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA

    Energy Technology Data Exchange (ETDEWEB)

    Ley, R.D. [The Lovelace Institutes, Albuqeurque, NM (United States). Photomdecine Program; Fourtanier, A. [L`Oreal, Advanced Research, Clichy (France)

    1997-06-01

    Solar ultraviolet radiation (UVR) induces a number of pathologic conditions of mammalian skin including erythema, oedema, hyperplasia, sunburn cell formation and skin cancer. Consequently, UVR-induced DNA damage has been implicated as one of the photochemical events that results in the formation of these pathological changes. The ability of sunscreens to protect against UVR-induced DNA damage has not been well characterized especially with UVA (320-400 nm) wavelengths and UVA absorbers. In this paper we present results of a study aimed at determining the efficacy of two sunscreens at preventing the induction of pyrmidine dimers in basal cell DNA of mice exposed to solar-simulated UVR (SSUV) wavelengths (290-400 nm) or to UVA (320-400 nm). (author).

  1. Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice.

    Science.gov (United States)

    Rahimian, Reza; Zirak, Mohammad Reza; Seyedabadi, Mohammad; Keshavarz, Mojtaba; Rashidian, Amir; Kazmi, Sareh; Jafarian, Amir Hossein; Karimi, Gholamreza; Mousavizadeh, Kazem

    2017-09-01

    Acute pancreatitis (AP) causes morbidity and mortality. The aim of the present study was to investigate the protective effect of tropisetron against AP induced by cerulein. Cerulein (50μg/kg, 5 doses) was used to induce AP in mice. Six hours after final cerulein injection, animals were decapitated. Hepatic/pancreatic enzymes in the serum, pancreatic content of malondialdehyde (MDA), pro-inflammatory cytokines and myeloperoxidase (MPO) activity were measured. Tropisetron significantly attenuated pancreatic injury markers and decreased the amount of elevated serum amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), MPO activities and pro-inflammatory cytokines levels caused by AP in mice. Tropisetron didn't affect the pancreatic levels of MDA. Our results suggest that tropisetron could attenuate cerulein-induced AP by combating inflammatory signaling. Further clinical studies are needed to confirm its efficacy in patients with AP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Laser-induced spin protection and switching in a specially designed magnetic dot: A theoretical investigation

    Science.gov (United States)

    Zhang, G. P.; Si, M. S.; George, T. F.

    2011-04-01

    Most laser-induced femtosecond magnetism investigations are done in magnetic thin films. Nanostructured magnetic dots, with their reduced dimensionality, present new opportunities for spin manipulation. Here we predict that if a magnetic dot has a dipole-forbidden transition between the lowest occupied molecular orbital (LUMO) and the highest unoccupied molecular orbital (HOMO), but a dipole-allowed transition between LUMO+1 and HOMO, electromagnetically induced transparency can be used to prevent ultrafast laser-induced spin momentum reduction, or spin protection. This is realized through a strong dump pulse to funnel the population into LUMO+1. If the time delay between the pump and dump pulses is longer than 60 fs, a population inversion starts and spin switching is achieved. These predictions are detectable experimentally.

  3. The protective effect of Physalis peruviana L. against cadmium-induced neurotoxicity in rats.

    Science.gov (United States)

    Abdel Moneim, Ahmed E; Bauomy, Amira A; Diab, Marwa M S; Shata, Mohamed Tarek M; Al-Olayan, Ebtesam M; El-Khadragy, Manal F

    2014-09-01

    The present study was carried out to investigate the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced neurotoxicity in rats. Adult male Wistar rats were randomly divided into four groups. Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg bwt of cadmium chloride for 5 days. Group 3 was treated with 200 mg/kg bwt of methanolic extract of Physalis (MEPh). Group 4 was pretreated with MEPh 1 h before cadmium for 5 days. Cadmium treatment induced marked disturbances in neurochemical parameters as indicating by significant (p Physalis has a beneficial effect in ameliorating the cadmium-induced oxidative neurotoxicity in the brain of rats.

  4. Hepatocyte growth factor protects human endothelial cells against advanced glycation end products-induced apoposis

    International Nuclear Information System (INIS)

    Zhou Yijun; Wang Jiahe; Zhang Jin

    2006-01-01

    Advanced glycation end products (AGEs) form by a non-enzymatic reaction between reducing sugars and biological proteins, which play an important role in the pathogenesis of atherosclerosis. In this study, we assessed AGEs effects on human umbilical vein endothelial cells (HUVECs) growth, proliferation and apoptosis. Additionally, we investigated whether hepatocyte growth factor (HGF), an anti-apoptotic factor for endothelial cells, prevents AGEs-induced apoptosis of HUVECs. HUVECs were treated with AGEs in the presence or absence of HGF. Treatment of HUVECs with AGEs changed cell morphology, decreased cell viability, and induced DNA fragmentation, leading to apoptosis. Apoptosis was induced by AGEs in a dose- and time-dependent fashion. AGEs markedly elevated Bax and decreased NF-κB, but not Bcl-2 expression. Additionally, AGEs significantly inhibited cell growth through a pro-apoptotic action involving caspase-3 and -9 activations in HUVECs. Most importantly, pretreatment with HGF protected against AGEs-induced cytotoxicity in the endothelial cells. HGF significantly promoted the expression of Bcl-2 and NF-κB, while decreasing the activities of caspase-3 and -9 without affecting Bax level. Our data suggest that AGEs induce apoptosis in endothelial cells. HGF effectively attenuate AGEs-induced endothelial cell apoptosis. These findings provide new perspectives in the role of HGF in cardiovascular disease

  5. The Structural Features of Sports and Race Betting Inducements: Issues for Harm Minimisation and Consumer Protection.

    Science.gov (United States)

    Hing, Nerilee; Sproston, Kerry; Brook, Kate; Brading, Richard

    2017-06-01

    Minimal research has been published about inducements for sports and race betting, despite their ready availability and aggressive advertising. This paper aimed to document the range and structural features of these inducements, and analyse their alignment with the harm minimisation and consumer protection goals of responsible gambling. A scan of all inducements offered on the websites of 30 major race and sports betting brands located 223 separate inducements which we categorised into 15 generic types, all offering financial incentives to purchase. These comprised sign-up offers, refer-a-friend offers, happy hours, mobile betting bonuses, multi-bet offers, refund/stake-back offers, matching stakes/deposits, winnings paid for 'close calls', bonus or better odds, bonus or better winnings, competitions, reduced commission, free bets to selected punters, cash rebates and other free bets. All inducements were subject to numerous terms and conditions which were complex, difficult to find, and obscured by legalistic language. Play-through conditions of bonus bets were particularly difficult to interpret and failed basic requirements for informed choice. Website advertisements for inducements were prominently promoted but few contained a responsible gambling message. The results were analysed to generate 12 research propositions considered worthy of empirical research to inform much needed regulatory reform in this area.

  6. Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism.

    Science.gov (United States)

    Wang, Yimin; Luo, Xiao; Pan, Hao; Huang, Wei; Wang, Xueping; Wen, Huali; Shen, Kezhen; Jin, Baiye

    2015-09-01

    Cisplatin induced nephrotoxicity is primarily caused by ROS (Reactive Oxygen Species) induced proximal tubular cell death. NADPH oxidase is major source of ROS production by cisplatin. Here, we reported that pharmacological inhibition of NADPH oxidase by acetovanillone (obtained from medicinal herb Picrorhiza kurroa) led to reduced cisplatin nephrotoxicity in mice. In this study we used various molecular biology and biochemistry methods a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Cisplatin-induced nephrotoxicity was evident by histological damage from loss of the tubular structure. The damage was also marked by the increase in blood urea nitrogen, creatinine, protein nitration as well as cell death markers such as caspase 3/7 activity and DNA fragmentation. Tubular cell death by cisplatin led to pro-inflammatory response by production of TNFα and IL1β followed by leukocyte/neutrophil infiltration which resulted in new wave of ROS involving more NADPH oxidases. Cisplatin-induced markers of kidney damage such as oxidative stress, cell death, inflammatory cytokine production and nephrotoxicity were attenuated by acetovanillone. In addition to that, acetovanillone enhanced cancer cell killing efficacy of cisplatin. Thus, pharmacological inhibition of NADPH oxidase can be protective for cisplatin-induced nephrotoxicity in mice. Copyright © 2015. Published by Elsevier Ltd.

  7. Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on delta-opioid receptor stimulation.

    Science.gov (United States)

    Panneerselvam, Mathivadhani; Tsutsumi, Yasuo M; Bonds, Jacqueline A; Horikawa, Yousuke T; Saldana, Michelle; Dalton, Nancy D; Head, Brian P; Patel, Piyush M; Roth, David M; Patel, Hemal H

    2010-11-01

    Epicatechin, a flavonoid, is a well-known antioxidant linked to a variety of protective effects in both humans and animals. In particular, its role in protection against cardiovascular disease has been demonstrated by epidemiologic studies. Low-dose epicatechin, which does not have significant antioxidant activity, is also protective; however, the mechanism by which low-dose epicatechin induces this effect is unknown. Our laboratory tested the hypothesis that low-dose epicatechin mediates cardiac protection via opioid receptor activation. C57BL/6 mice were randomly assigned to 1 of 10 groups: control, epicatechin, naloxone (nonselective opioid receptor antagonist), epicatechin + naloxone, naltrindole (δ-specific opioid receptor antagonist), epicatechin + naltrindole, norbinaltorphimine (nor-BNI, κ-specific opioid receptor antagonist), epicatechin + nor-BNI, 5-hydroxydecanoic acid [5-HD, ATP-sensitive potassium channel antagonist], and epicatechin + 5-HD. Epicatechin (1 mg/kg) or other inhibitors (5 mg/kg) were administered by oral gavage or intraperitoneal injection, respectively, daily for 10 days. Mice were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion, and infarct size was determined via planimetry. Whole heart homogenates were assayed for downstream opioid receptor signaling targets. Infarct size was significantly reduced in epicatechin- and epicatechin + nor-BNI-treated mice compared with control mice. This protection was blocked by naloxone, naltrindole, and 5-HD. Epicatechin and epicatechin + nor-BNI increased the phosphorylation of Src, Akt, and IκBα, while simultaneously decreasing the expression of c-Jun NH(2)-terminal kinase and caspase-activated DNase. All signaling effects are consistent with opioid receptor stimulation and subsequent cardiac protection. Naloxone, naltrindole, and 5-HD attenuated these effects. In conclusion, epicatechin acts via opioid receptors and more specifically through the δ-opioid receptor to

  8. Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies.

    Science.gov (United States)

    Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A

    2017-10-15

    Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody

  9. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

    Energy Technology Data Exchange (ETDEWEB)

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Shahverdi, Ahmad Reza [Department of Pharmaceutical Biotechnology and Biotechnology Research Centre, Faculty of Pharmacy, TUMS, Tehran (Iran, Islamic Republic of); Ahmadi, Abbas [Department of Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia (Iran, Islamic Republic of); Baeeri, Maryam; Mohammadirad, Azadeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: mohammad.abdollahi@utoronto.ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of)

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. Highlights: ► Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ► Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ► CIS-exposure induces oxidative sperm DNA damage

  10. Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

    Science.gov (United States)

    Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

    2018-01-01

    A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

  11. Rhynchophylline Protects Against the Amyloid β-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats.

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    Shao, Hui; Mi, Ze; Ji, Wei-gang; Zhang, Cheng-huan; Zhang, Teng; Ren, Shuan-cheng; Zhu, Zhi-ru

    2015-11-01

    Accumulated soluble amyloid β (Aβ)-induced aberrant neuronal network activity has been recognized as a key causative factor leading to cognitive deficits which are the most outstanding characteristic of Alzheimer's disease (AD). As an important structure associated with learning and memory, the hippocampus is one of the brain regions that are impaired very early in AD, and the hippocampal CA1 region is selectively vulnerable to soluble Aβ oligomers. Our recent study showed that soluble Aβ1-42 oligomers induced hyperactivity and perturbed the firing patterns in hippocampal neurons. Rhynchophylline (RIN) is an important active tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla which is a traditional Chinese medicine and often used to treat central nervous system illnesses such as hypertension, convulsions, tremor, stroke etc. Previous evidence showed that RIN possessed neuroprotective effects of improving the cognitive function of mice with Alzheimer-like symptoms. In the present study, we aimed to investigate the protective effect of RIN against soluble Aβ1-42 oligomers-induced hippocampal hyperactivity. The results showed that (1) the mean frequency of spontaneous discharge was increased by the local application of 3 μM soluble Aβ1-42 oligomers; (2) 30 μM RIN did not exert any obvious effects on basal physiological discharges; and (3) treatment with RIN effectively inhibited the soluble Aβ1-42 oligomers-induced enhancement of spontaneous discharge, in a concentration-dependent manner with an IC50 = 9.0 μM. These in vivo electrophysiological results indicate that RIN can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ1-42 on neural circuit. The experimental findings provide further evidence to affirm the potential of RIN as a worthy candidate for further development into a therapeutic agent for AD.

  12. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  13. Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus.

    Science.gov (United States)

    Khalaj, Leila; Nejad, Sara Chavoshi; Mohammadi, Marzieh; Zadeh, Sadaf Sarraf; Pour, Marieh Hossein; Ahmadiani, Abolhassan; Khodagholi, Fariba; Ashabi, Ghorbangol; Alamdary, Shabnam Zeighamy; Samami, Elham

    2013-08-21

    Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. It also reduced plasma corticosterone compared with the stressed animals. Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner.

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    Samit Chatterjee

    2011-11-01

    Full Text Available Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG has been used as a tuberculosis (TB vaccine since its development in 1921. BCG induces robust T helper 1 (Th1 immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6, expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1 exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1. However, TLR-2 knockout (TLR-2⁻/⁻ animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a in dendritic cells (DCs, whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy.

  15. EFFECTS OF RUMEN PROTECTED METHIONINE AND VITAMIN B12 ON RBC PARAMETERS OF DAIRY COWS IN EARLY LACTATION

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    Morteza Safarkhanlou

    2016-12-01

    Full Text Available To study the effects of rumen-protected methionine and vitamin B12 as well as their interactions on the parameters of red blood cells of dairy cows in early lactation, 16 Holstein cows in early lactation in experiment with randomized complete block design with the 2×2 factorial arrangement used for 42 days. In this experiment, there were four treatments, which in each treatment is placed two cows primi-parous and two cows multi-parous. Treatments included: 1 The group receiving the basal diet, 2 The group receiving the basal diet with vitamin B12 injections, 3 The group receiving the basal diet with rumen-protected methionine, 4 The group receiving the basal diet with vitamin B12 injections and rumen-protected methionine. The results showed that in the use of vitamin B12 and rumen-protected methionine, there is no significant difference between the experimental groups in the number of red blood cells, hemoglobin levels and blood hematocrit. Mean corpuscular (cell volume and mean corpuscular (cell hemoglobin did increase with vitamin B12 supplementation. In a general conclusion, it seems that increasing MCV and MCH may result in improvement in oxygenation and in turn lead to improvement on dry matter intake and milk production.

  16. Coenzyme Q10 protects retinal cells from apoptosis induced by radiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Lulli, M.; Witort, E.; Papucci, L.; Torre, E.; Schiavone, N.; Capaccioli, S.; Dal Monte, M.

    2012-01-01

    The key pathogenetic event of many retinopathies is apoptosis of retinal cells. Our previous studies have demonstrated that Coenzyme Q10 (CoQ10) prevents apoptosis of corneal keratocytes both in vitro and in vivo, by virtue of its ability to inhibit mitochondrial depolarization, independently of its free radical scavenger role. The aim of this study was to evaluate whether CoQ10 can protect cultured retinal cells and the retinas of rats from radiation-induced apoptosis, if instilled as eye drops in the cornea. In vitro experiments were carried out on cultured ARPE-19 or retinal ganglion cells (RGC)-5 cells pretreated with CoQ10 before eliciting apoptosis by ultraviolet (UV)- and γ-radiation, chemical hypoxia (Antimycin A) and serum starvation. Cell viability was evaluated by light microscopy and fluorescence activated cell sorting analysis. Apoptotic events were scored by time-lapse videomicroscopy. Mitochondrial permeability transition was evaluated by JC-1. The anti-apoptotic effectiveness of CoQ10 in retina was also evaluated by an in situ end-labeling assay in Wistar albino rats treated with CoQ10 eye drops prior to UV irradiation of the eye. CoQ10 substantially increased cell viability and lowered retinal cell apoptosis in response both to UV- and γ-radiation and to chemical hypoxia or serum starvation by inhibiting mitochondrion depolarization. In the rat, CoQ10, even when applied as eye drops on the cornea, protected all retina layers from ultraviolet radiation (UVR)-induced apoptosis. The ability of CoQ10 to protect retinal cells from radiation-induced apoptosis following its instillation on the cornea suggests the possibility for CoQ10 eye drops to become a future therapeutic countermeasure for radiation-induced retinal lesions. (author)

  17. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

    Science.gov (United States)

    Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

    2013-08-01

    The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

  18. Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in rat models.

    Science.gov (United States)

    Liu, Xinwen; Huang, Zhenguang; Zou, Xiaoqin; Yang, Yufang; Qiu, Yue; Wen, Yan

    2015-01-01

    This study investigates the mechanism of the protective effect of Panax notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a single dose of cisplatin and a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the concentrations of urinary N-acetyl-β-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue was examined using H&E-staining, and the mitochondria of renal tubular epithelial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein-1 light chain (LC)3, autophagy-related gene (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western blotting. The expression of HIF-1 was detected by immunohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and Scr, the attenuation of renal histopathological changes and the mitochondrial damages of renal cells, and the increase of mitochondria autophagosome in renal tubular epithelial cells. Additionally, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5 and Beclin-1 in rat renal tissue. In conclusion, the protective effect of PNS on cisplatin-induced nephrotoxicity was mainly due to its ability to enhancing the mitochondrial autophagy of renal tissue via the HIF-1α/BNIP3 pathway, and here is the first demonstration about it.

  19. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

    Science.gov (United States)

    Bedarida, Tatiana; Domingues, Alison; Baron, Stephanie; Ferreira, Chrystophe; Vibert, Francoise; Cottart, Charles-Henry; Paul, Jean-Louis; Escriou, Virginie; Bigey, Pascal; Gaussem, Pascale; Leguillier, Teddy; Nivet-Antoine, Valerie

    2018-06-01

    Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP fl/fl cdh5 cre ). Control (TXNIP fl/fl ) and TXNIP fl/fl cdh5 cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIP fl/fl and TXNIP fl/fl cdh5 cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIP fl/fl cdh5 cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

  20. Maintaining Traditions: A Qualitative Study of Early Childhood Caries Risk and Protective Factors in an Indigenous Community.

    Science.gov (United States)

    Levin, Ana; Sokal-Gutierrez, Karen; Hargrave, Anita; Funsch, Elizabeth; Hoeft, Kristin S

    2017-08-11

    In lower middle-income economies (LMIE), the nutrition transition from traditional diets to sugary foods and beverages has contributed to widespread early childhood dental caries. This qualitative study explores perceived risk and protective factors, and overall experiences of early childhood nutrition and oral health in indigenous Ecuadorian families participating in a community-based oral health and nutrition intervention. Dental exams of 698 children age 6 months through 6 years determined each child's caries burden. A convenience sample of 18 "outlier" families was identified: low-caries children with ≤2 carious teeth vs. high-caries children with ≥10 carious teeth. Semi-structured in-depth interviews with parents/caregivers explored the child's diet, dental habits, and family factors related to nutrition and oral health. Interviews were transcribed and thematically analyzed using grounded theory. In the high-caries families, proximity to highway and stores, consumption of processed-food, and low parental monitoring of child behavior were identified as risk factors for ECC (early childhood caries). In the low-caries families, protective factors included harvesting and consuming food from the family farm, remote geography, and greater parental monitoring of child behavior. The study results suggest that maintaining traditional family farms and authoritative parenting to avoid processed foods/drinks and ensure tooth brushing could improve early childhood nutrition and oral health.

  1. IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease

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    Kim Byung S

    2012-09-01

    Full Text Available Abstract Background Theiler’s virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS. IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease. Methods Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO were infected with Theiler’s murine encephalomyelitis virus (1 x 106 PFU. Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry. Results Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6 mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence. Conclusions These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of

  2. Protective efficacy of Aloe vera against radiation and cadmium induced haematological changes in the Swiss Albino mice

    International Nuclear Information System (INIS)

    Agarwal, Manisha; Purohit, R.K.; Chakrawarti, Aruna; Basu, Arindam; Bhartiya, K.M.

    2011-01-01

    The aim of the present study was to evaluate the protective effect of Aloe vera against radiation and cadmium induced haematological changes in the Swiss albino mice; 6-8 weeks old animals from each of the experimental groups were sacrificed by cervical dislocation at each post treatment intervals of 1,2,4,7,14 and 28 day. After sacrificing the animals, the blood was collected by cardiac puncture in heparinized tubes for various haematological studies. The values of RBC, WBC, Haemoglobin and PCV were found to decrease up to day-14 in non drug treated groups (II,III and IV), thereafter they increased on day-28. Whereas the values decreased upto day-7 in Aloe vera treated groups (V,VI,VlI) thereafter increased tip to day-28. On the other hand, the value of MCV increased upto day- 14 in non-drug treated groups (II, III, IV) and tip to day-7 in drug treated groups (V, VI, VII), thereafter it decreased tip to day-28. After combined treatment of radiation and cadmium chloride synergistic effects were observed. The Aloe vera treated animals exhibited less severe damage as compared to non-drug treated animals at all the corresponding intervals. An early and fast recovery was noticed in Aloe vera pretreated animals. Thus, it appears that Aloe vera is potent enough to check cadmium and radiation induced haematological changes in the Swiss albino mice. (author)

  3. Myocardial CKIP-1 Overexpression Protects from Simulated Microgravity-Induced Cardiac Remodeling

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    Shukuan Ling

    2018-01-01

    Full Text Available Human cardiovascular system has adapted to Earth's gravity of 1G. The microgravity during space flight can induce cardiac remodeling and decline of cardiac function. At present, the mechanism of cardiac remodeling induced by microgravity remains to be disclosed. Casein kinase-2 interacting protein-1 (CKIP-1 is an important inhibitor of pressure-overload induced cardiac remodeling by decreasing the phosphorylation level of HDAC4. However, the role of CKIP-1 in the cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether CKIP-1 was also involved in the regulation of cardiac remodeling induced by microgravity. We first detected the expression of CKIP-1 in the heart from mice and monkey after simulated microgravity using Q-PCR and western blotting. Then, myocardial specific CKIP-1 transgenic (TG and wild type mice were hindlimb-suspended (HU to simulate microgravity effect. We estimated the cardiac remodeling in morphology and function by histological analysis and echocardiography. Finally, we detected the phosphorylation of AMPK, ERK1/2, and HDAC4 in the heart from wild type and CKIP-1 transgenic mice after HU. The results revealed the reduced expression of CKIP-1 in the heart both from mice and monkey after simulated microgravity. Myocardial CKIP-1 overexpression protected from simulated microgravity-induced decline of cardiac function and loss of left ventricular mass. Histological analysis demonstrated CKIP-1 TG inhibited the decreases in the size of individual cardiomyocytes of mice after hindlimb unloading. CKIP-1 TG can inhibit the activation of HDAC4 and ERK1/2 and the inactivation of AMPK in heart of mice induced by simulated microgravity. These results demonstrated CKIP-1 was a suppressor of cardiac remodeling induced by simulated microgravity.

  4. Can VHS Virus Bypass the Protective Immunity Induced by DNA Vaccination in Rainbow Trout?

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    Dagoberto Sepúlveda

    Full Text Available DNA vaccines encoding viral glycoproteins have been very successful for induction of protective immunity against diseases caused by rhabdoviruses in cultured fish species. However, the vaccine concept is based on a single viral gene and since RNA viruses are known to possess high variability and adaptation capacity, this work aimed at evaluating whether viral haemorrhagic septicaemia virus (VHSV, an RNA virus and member of Rhabdoviridae family, was able to evade the protective immune response induced by the DNA vaccination of rainbow trout. The experiments comprised repeated passages of a highly pathogenic VHSV isolate in a fish cell line in the presence of neutralizing fish serum (in vitro approach, and in rainbow trout immunized with the VHS DNA vaccine (in vivo approach. For the in vitro approach, the virus collected from the last passage (passaged virus was as sensitive as the parental virus to serum neutralization, suggesting that the passaging did not promote the selection of virus populations able to bypass the neutralization by serum antibodies. Also, in the in vivo approach, where virus was passaged several times in vaccinated fish, no increased virulence nor increased persistence in vaccinated fish was observed in comparison with the parental virus. However, some of the vaccinated fish did get infected and could transmit the infection to naïve cohabitant fish. The results demonstrated that the DNA vaccine induced a robust protection, but also that the immunity was non-sterile. It is consequently important not to consider vaccinated fish as virus free in veterinary terms.

  5. Hypercholesterolemic myocardium is vulnerable to ischemia-reperfusion injury and refractory to sevoflurane-induced protection.

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    Yong Xu

    Full Text Available Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR injury through activation of the reperfusion injury salvage kinase (RISK pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.

  6. Citrus bergamia Risso & Poiteau juice protects against renal injury of diet-induced hypercholesterolemia in rats.

    Science.gov (United States)

    Trovato, Ada; Taviano, Maria F; Pergolizzi, Simona; Campolo, Loredana; De Pasquale, Rita; Miceli, Natalizia

    2010-04-01

    The present study was designed to evaluate the protective effect of treatment with Citrus bergamia juice (1 mL/day, for 30 days) against hypercholesterolemic diet-induced renal injury in rat.C. bergamia juice provoked a significant reduction in the plasma levels of cholesterol, triglycerides and LDL, and an increase in HDL levels, versus hyperlipidemic controls (p juice administration significantly decreased MDA levels elevations compared with hyperlipidemic controls (4.10 +/- 0.10 nmol/mg protein and 4.78 +/- 0.15 nmol/mg protein, respectively).Histological observations of the kidney supported the biochemical data and indicated a protective effect of C. bergamia juice on the development of renal damage in hypercholesterolemic rats.The antioxidant potential of C. bergamia juice was examined in two in vitro systems: in the DPPH test the juice showed a noticeable effect on scavenging free radicals (IC(50) = 25.01 +/- 0.70 +/-L); in the reducing power assay it showed a strong activity, too (1.44 +/- 0.01 ASE/mL).These findings suggest that C. bergamia juice has a protective role in hypercholesterolemic diet-induced renal damage, which may be attributed to its antioxidant properties. Copyright (c) 2009 John Wiley & Sons, Ltd.

  7. Study of protective effects of melatonin on cisplatin-induced nephrotoxicity in rabbits

    International Nuclear Information System (INIS)

    Aslam, J.; Khan, W.; Bakhtiar, S.

    2017-01-01

    To evaluate the protective effects of melatonin on cisplatin-induced nephrotoxicity in rabbits. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Pharmacology and Therapeutics in collaboration with Clinico Pathologic Laboratory, Army Medical College, Rawalpindi, from Apr to Jun 2015. Material and Methods: Eighteen rabbits were divided into three groups, each consisting of six rabbits. Baseline serum urea, creatinine, sodium and potassium were measured. Rabbits were weighed for dose calculation. A single dose of cisplatin 10mg/kg was given as I/P injection to the toxic group. The protective group received 5 mg/kg I/P melatonin for three days. Rabbits were sacrificed 72 hours after the cisplatin dose and both kidneys were sent for histopathology. Statistical analysis was carried out by using Microsoft Office Excel 2010 and SPSS version 21. Student's t-test and one way ANOVA, followed by 'Post Hoc Tukey' test was used for biochemical parameters, while Chi Square' test was used for histopathological comparison. Results: Moderate nephrotoxicity (grade-II) was seen in the toxic group, with substantial elevations of serum urea and creatinine (p<0.001), and serum sodium and potassium (p<0.01). Melatonin ameliorated the renal injury. Conclusion: The protective effects of melatonin on cisplatin-induced nephrotoxicity were due to its antioxidant properties. (author)

  8. Melatonin protect the development of preimplantation mouse embryos from sodium fluoride-induced oxidative injury.

    Science.gov (United States)

    Zhao, Jiamin; Fu, Beibei; Peng, Wei; Mao, Tingchao; Wu, Haibo; Zhang, Yong

    2017-09-01

    Recently study shows that melatonin can protect embryos from the culture environment oxidative stress. However, the protective effect of melatonin on the mouse development of preimplantation embryos under sodium fluoride (NaF) induced oxidative stress is still unclear. Here, we showed that exposure to NaF significantly increased the reactive oxygen species (ROS) level, decreased the blastocyst formation rates, and increased the fragmentation, apoptosis and retardation of blastocysts in the development of mouse preimplantation embryos. However, the protective of melatonin remarkable increased the of blastocyst formation rates, maintained mitochondrial function and total antioxidant capacity by clearing ROS. Importantly the data showed that melatonin improved the activity of enzymatic antioxidants, including glutathione(GSH), superoxide dismutase(SOD), and malonaldehyde (MDA), and increased the expression levels of antioxidative genes. Taken together, our results indicate that melatonin prevent NaF-induced oxidative damage to mouse preimplantation embryo through down regulation of ROS level, stabilization of mitochondrial function and modulation of the activity of antioxidases and antioxidant genes. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    Directory of Open Access Journals (Sweden)

    Zun-Jing Liu

    2013-01-01

    Full Text Available Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

  10. The primary study on protective effects of vallinin derivative on cell injury induced by radiation

    International Nuclear Information System (INIS)

    Zheng Hong; Wang Siying; Yan Yuqian; Wang Lin; Xu Qinzhi; Cong Jianbo; Zhou Pingkun

    2008-01-01

    In this paper, the protective effects of vallinin derivative VND3207 on cell injury induced by radiation were studied by the methods of methyl thiazolyl tetrazolium colorimetric assay (MTT) and electron spin resonance (ESR). At first, MTF method was used to evaluate the cytotoxicity of vallinin derivatives (VND3202-VND3209) in HFS cells. Then, MTT method was used to measure the proliferation activity of HeLa cells with 2 Gy irradiation treated with vallinin derivatives and measure the proliferation of AHH-1 cells treated with VND3207 before exposed to 4 Gy irradiation. And ESR detected the antioxidation activity of vallinin and VND3207. The results showed that VND3207 and VND3206 presented no toxin within 50 panol/L, and VND3207 and VND3209 had no proliferous effects on HeLa cells while VND3206 could expedite the tumor cell proliferation at 30 μmol/L, and by comrades VND3208 showed increased radiosensitivity of the HeLa cells. For the AHH1 cells exposed to 4 Gy irradiation, VND3207 presented the protective effects against radiation injury. ESR results also suggested that VND3207 could clean out free radicals. Its effect was far more potent than that of vanillin. From this study we primarily screened out the vallinin derivative VND3207 which has protective effects on cell injury induced by radiation and provided data for future research work. (authors)

  11. UVA-induced protection of skin through the induction of heme oxygenase-1.

    Science.gov (United States)

    Xiang, Yuancai; Liu, Gang; Yang, Li; Zhong, Julia Li

    2011-12-01

    UVA (320-400 nm) and UVB (290-320 nm) are the major components of solar UV irradiation, which is associated with various pathological conditions. UVB causes direct damage to DNA of epidermal cells and is mainly responsible for erythema, immunosuppression, photoaging, and skin cancer. UVA has oxidizing properties that can cause damage or enhance UVB damaging effects on skin. On the other hand, UVA can also lead to high levels of heme oxygenase-1 (HO-1) expression of cells that can provide an antioxidant effect on skin as well as anti-inflammatory properties in mammals and rodents. Therefore, this review focuses on the potential protection of UVA wavebands for the skin immune response, instead of mechanisms that underlie UVA-induced damage. Also, the role of HO-1 in UVA-mediated protection against UVB-induced immunosuppression in skin will be summarized. Thus, this review facilitates further understanding of potential beneficial mechanisms of UVA irradiation, and using the longer UVA (UVA1, 340-400 nm) in combination with HO-1 for phototherapy and skin protection against sunlight exposure.

  12. Bursopentin (BP5 protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.

    Directory of Open Access Journals (Sweden)

    Tao Qin

    Full Text Available Dendritic cells (DCs play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5, a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD, were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1 was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

  13. Protective efficacy of Emblica against radiation and lead induced biochemical changes in the kidney of Swiss albino mice

    International Nuclear Information System (INIS)

    Chakrawarti, Aruna; Dev, Rahul; Rathore, Narendra Singh; Khatri, Anand

    2012-01-01

    Ionizing radiation kills cells in the area being treated (the target tissue) as well as other surrounding healthy cells. The damaging effects of ionizing radiation on healthy tissue create a major barrier in effective treatment of common human cancers. Thus there is a need to find a safe and highly effective avenue to reduce normal cell damage during cancer therapy, plants have been used in the traditional healthcare system from time immemorial, and phyto products continue to play an essential role in medicine. Emblica, is reported to have an excellent radio protective activity, antioxidant and a free radical scavenger. In light of above, the present study was aimed to evaluate the protective effect of Emblica against radiation and lead induced biochemical alterations in the kidney of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays with or without Lead acetate treatment. The Emblica was administered seven days prior to irradiation or Lead Acetate treatment. The animals from all experimental groups were sacrificed by cervical dislocation at each post treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals, pieces of the kidney were taken out and kept at - 20 deg C for different biochemical parameters. For the study the animals were exposed to 6.0 Gy of gamma rays with or without Lead acetate treatments. In the experimental groups the Emblica juice was given seven days prior to the radiation or lead acetate treatment. The various biochemical parameters viz, total proteins, glycogen, cholesterol, acid phosphatase and alkaline phosphatase activities, DNA and RNA were estimated. The values were observed in the form of increase or decrease. After combined treatment of radiation and lead acetate the changes were more severe showing synergistic effect of both the agent. An early and fast recovery was also noticed in Emblica pre-treated animals. Thus it appears that Emblica is potent enough to check Lead and Radiation induced

  14. Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis.

    Science.gov (United States)

    Agrawal, L; Louboutin, J-P; Reyes, B A S; Van Bockstaele, E J; Strayer, D S

    2006-12-01

    Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. As they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells and primary fetal neurons were transduced with rSV40 vectors carrying human SOD1 and/or GPx1 cDNAs, then exposed to gp120. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Transduction efficiency of both neuron populations was >95%, as assayed by immunostaining. Transgene expression was also ascertained by Western blotting and direct assays of enzyme activity. Gp120 induced apoptosis in a high percentage of unprotected NT2-N. Transduction with SV(SOD1) and SV(GPx1) before gp120 challenge reduced neuronal apoptosis by >90%. Even greater protection was seen in cells treated with both vectors in sequence. Given singly or in combination, they protect neuronal cells from HIV-1-gp120 induced apoptosis. We tested whether rSV40 s can deliver antioxidant enzymes to the CNS in vivo: intracerebral injection of SV(SOD1) or SV(GPx1) into the caudate putamen of rat brain yielded excellent transgene expression in neurons. In vivo transduction using SV(SOD1) also protected neurons from subsequent gp120-induced apoptosis after injection of both into the caudate putamen of rat brain. Thus, SOD1 and GPx1 can be delivered by SV40 vectors in vitro or in vivo. This approach may merit consideration for

  15. Fluoxetine protects against IL-1β-induced neuronal apoptosis via downregulation of p53.

    Science.gov (United States)

    Shan, Han; Bian, Yaqi; Shu, Zhaoma; Zhang, Linxia; Zhu, Jialei; Ding, Jianhua; Lu, Ming; Xiao, Ming; Hu, Gang

    2016-08-01

    Fluoxetine, a selective serotonin reuptake inhibitor, exerts neuroprotective effects in a variety of neurological diseases including stroke, but the underlying mechanism remains obscure. In the present study, we addressed the molecular events in fluoxetine against ischemia/reperfusion-induced acute neuronal injury and inflammation-induced neuronal apoptosis. We showed that treatment of fluoxetine (40 mg/kg, i.p.) with twice injections at 1 h and 12 h after transient middle cerebral artery occlusion (tMCAO) respectively alleviated neurological deficits and neuronal apoptosis in a mouse ischemic stroke model, accompanied by inhibiting interleukin-1β (IL-1β), Bax and p53 expression and upregulating anti-apoptotic protein Bcl-2 level. We next mimicked neuroinflammation in ischemic stroke with IL-1β in primary cultured cortical neurons and found that pretreatment with fluoxetine (1 μM) prevented IL-1β-induced neuronal apoptosis and upregulation of p53 expression. Furthermore, we demonstrated that p53 overexpression in N2a cell line abolished the anti-apoptotic effect of fluoxetine, indicating that p53 downregulation is required for the protective role of fluoxetine in IL-1β-induced neuronal apoptosis. Fluoxetine downregulating p53 expression could be mimicked by SB203580, a specific inhibitor of p38, but blocked by anisomycin, a p38 activator. Collectively, our findings have revealed that fluoxetine protects against IL-1β-induced neuronal apoptosis via p38-p53 dependent pathway, which give us an insight into the potential of fluoxetine in terms of opening up novel therapeutic avenues for neurological diseases including stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Downregulation of Lysyl Oxidase Protects Retinal Endothelial Cells From High Glucose-Induced Apoptosis.

    Science.gov (United States)

    Kim, Dongjoon; Mecham, Robert P; Trackman, Philip C; Roy, Sayon

    2017-05-01

    To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to β-aminopropionitrile (BAPN), a LOX inhibitor. LOX expression, AKT activation, and caspase-3 activity were determined by Western blot (WB) analysis and apoptosis by differential dye staining assay. Moreover, to determine whether diabetes-induced LOX overexpression alters AKT activation and promotes apoptosis, changes in LOX expression, AKT phosphorylation, caspase-3 activation, and Bax expression were assessed in retinas of streptozotocin (STZ)-induced diabetic mice and LOX heterozygous knockout (LOX+/-) mice. WB analysis indicated significant LOX overexpression and reduced AKT activation under HG condition in RRECs. Interestingly, when cells grown in HG were transfected with LOX siRNA or exposed to BAPN, the number of apoptotic cells was significantly decreased concomitant with increased AKT phosphorylation. Diabetic mouse retinas exhibited LOX overexpression, decreased AKT phosphorylation, and increased Bax and caspase-3 activation compared to values in nondiabetic mice. In LOX+/- mice, reduced LOX levels were observed with increased AKT activity, and reduced Bax and caspase-3 activity. Furthermore, decreased levels of LOX in the LOX+/- mice was protective against diabetes-induced apoptosis. Findings from this study indicate that preventing LOX overexpression may be protective against HG-induced apoptosis in retinal vascular cells associated with diabetic retinopathy.

  17. Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

    Science.gov (United States)

    Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

    2015-06-01

    Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2). © 2015 International Society for Neurochemistry.

  18. Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

    International Nuclear Information System (INIS)

    Dudek, E.J.; Roth, R.M.

    1990-01-01

    Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs

  19. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways.

    Science.gov (United States)

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-03-25

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

  20. The Protective Effect of Gangliosides on Lead (Pb-Induced Neurotoxicity Is Mediated by Autophagic Pathways

    Directory of Open Access Journals (Sweden)

    Hongtao Meng

    2016-03-01

    Full Text Available Lead (Pb is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

  1. Estrogen protects the liver and intestines against sepsis-induced injury in rats.

    Science.gov (United States)

    Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

    2005-09-01

    Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

  2. Pomegranate Intake Protects Against Genomic Instability Induced by Medical X-rays In Vivo in Mice.

    Science.gov (United States)

    Nallanthighal, Sameera; Shirode, Amit B; Judd, Julius A; Reliene, Ramune

    2016-01-01

    Ionizing radiation (IR) is a well-documented human carcinogen. The increased use of IR in medical procedures has doubled the annual radiation dose and may increase cancer risk. Genomic instability is an intermediate lesion in IR-induced cancer. We examined whether pomegranate extract (PE) suppresses genomic instability induced by x-rays. Mice were treated orally with PE and exposed to an x-ray dose of 2 Gy. PE intake suppressed x-ray-induced DNA double-strand breaks (DSBs) in peripheral blood and chromosomal damage in bone marrow. We hypothesized that PE-mediated protection against x-ray-induced damage may be due to the upregulation of DSB repair and antioxidant enzymes and/or increase in glutathione (GSH) levels. We found that expression of DSB repair genes was not altered (Nbs1 and Rad50) or was reduced (Mre11, DNA-PKcs, Ku80, Rad51, Rad52 and Brca2) in the liver of PE-treated mice. Likewise, mRNA levels of antioxidant enzymes were reduced (Gpx1, Cat, and Sod2) or were not altered (HO-1 and Sod1) as a function of PE treatment. In contrast, PE-treated mice with and without IR exposure displayed higher hepatic GSH concentrations than controls. Thus, ingestion of pomegranate polyphenols is associated with inhibition of x-ray-induced genomic instability and elevated GSH, which may reduce cancer risk.

  3. Protective effects of agmatine on lipopolysaccharide-injured microglia and inducible nitric oxide synthase activity.

    Science.gov (United States)

    Ahn, Soo Kyung; Hong, Samin; Park, Yu Mi; Choi, Ja Yong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2012-12-17

    Proinflammatory factors released from activated microglia contribute to maintaining homeostasis against various noxious stimuli in the central nervous system. If excessive, however, they may initiate a pathologic neuroinflammatory process. In this investigation, we evaluated whether agmatine, a primary polyamine known to protect neurons, reduces lipopolysaccharide (LPS)-induced damage to microglia in vitro and in vivo. For in vitro study, BV2-immortalized murine microglia were exposed to LPS with agmatine treatment. After 24hours, cell viability and the amount of nitrite generated were determined. For in vivo study, LPS was microinjected into the corpus callosum of adult male albino mice. Agmatine was intraperitoneally administered at the time of injury. Brains were evaluated 24hours after LPS microinjection to check for immunoreactivity with a microglial marker of ionized calcium binding adaptor molecule 1 (Iba1) and inducible nitric oxide synthase (iNOS). Using western blot analysis, protein expression of iNOS as well as that of the proinflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was determined. Agmatine significantly reduced the LPS-induced BV2 microglial cytotoxicity from over 80% to less than 60% (pAgmatine also decreased the activities of microglia and iNOS induced by LPS microinjection into corpus callosum. Our findings reveal that agmatine attenuates LPS-induced microglial damage and suggest that agmatine may serve as a novel therapeutic strategy for neuroinflammatory diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Sharma, Surendra Kr; Goyal, Naveen

    2012-05-01

    The aim of the present study was to evaluate the nephroprotective effect of methanolic extract of Heliotropium eichwaldii (MHE) in mice with cisplatin-induced acute renal damage. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (16mg/kg). Swiss albino mice were injected with vehicle, cisplatin, cisplatin plus MHE 200 mg/kg and cisplatin plus MHE 400mg/kg, respectively. MHE was administered for 7 d at a dose of 200 and 400 mg/kg per day orally starting 4 d before cisplatin injection. Animals were sacrificed 3d after treatment and blood as well as kidney tissue was isolated and analyzed. The various parameters such as blood urea nitrogen (BUN), serum creatinine (CRE), malondialdehyde (MDA), and catalase (CAT) and superoxide dismutase (SOD) activities were analyzed. MHE treatment significantly reduced BUN and serum CRE levels elevated by cisplatin administration (P<0.05). Also, it significantly attenuated cisplatin-induced increase in MDA level and improved the decreased CAT and SOD activities in renal cortical homogenates (P<0.05). Additionally, histopathological examination and scoring showed that MHE markedly ameliorated cisplatin-induced renal tubular necrosis. MHE can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin.

  5. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    International Nuclear Information System (INIS)

    Chen, Yi; Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi; Jing, Qian; Yue, Jiaqi; Liu, Yang; Cheng, Zhong; Li, Jingyi; Song, Haixing; Li, Guoyu; Liu, Rui; Wang, Jinhui

    2016-01-01

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  6. Bee Venom Protects against Rotenone-Induced Cell Death in NSC34 Motor Neuron Cells

    Directory of Open Access Journals (Sweden)

    So Young Jung

    2015-09-01

    Full Text Available Rotenone, an inhibitor of mitochondrial complex I of the mitochondrial respiratory chain, is known to elevate mitochondrial reactive oxygen species and induce apoptosis via activation of the caspase-3 pathway. Bee venom (BV extracted from honey bees has been widely used in oriental medicine and contains melittin, apamin, adolapin, mast cell-degranulating peptide, and phospholipase A2. In this study, we tested the effects of BV on neuronal cell death by examining rotenone-induced mitochondrial dysfunction. NSC34 motor neuron cells were pretreated with 2.5 μg/mL BV and stimulated with 10 μM rotenone to induce cell toxicity. We assessed cell death by Western blotting using specific antibodies, such as phospho-ERK1/2, phospho-JNK, and cleaved capase-3 and performed an MTT assay for evaluation of cell death and mitochondria staining. Pretreatment with 2.5 μg/mL BV had a neuroprotective effect against 10 μM rotenone-induced cell death in NSC34 motor neuron cells. Pre-treatment with BV significantly enhanced cell viability and ameliorated mitochondrial impairment in rotenone-treated cellular model. Moreover, BV treatment inhibited the activation of JNK signaling and cleaved caspase-3 related to cell death and increased ERK phosphorylation involved in cell survival in rotenone-treated NSC34 motor neuron cells. Taken together, we suggest that BV treatment can be useful for protection of neurons against oxidative stress or neurotoxin-induced cell death.

  7. Protective Roles of N-acetyl Cysteine and/or Taurine against Sumatriptan-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Javad Khalili Fard

    2016-12-01

    Full Text Available Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening. Results: It was revealed that liver toxicity induced by sumatriptan in in freshly isolated parenchymal hepatocytes is dose-dependent. Sumatriptan caused significant free radical generation followed by lipid peroxide formation, mitochondrial injury as well as lysosomal damage. Moreover, sumatriptan reduced cellular glutathione content. Taurine and N-acetyl cysteine were able to protect hepatocytes against sumatriptan-induced harmful effects. Conclusion: It is concluded that sumatriptan causes oxidative stress in hepatocytes and the decreased hepatocytes glutathione has a key role in the sumatriptan-induced harmful effects. Also, N-acetyl cysteine and/or taurine could be used as treatments in sumatriptan-induced side effects.

  8. Nitric oxide protects anterior pituitary cells from cadmium-induced apoptosis.

    Science.gov (United States)

    Poliandri, Ariel H B; Velardez, Miguel O; Cabilla, Jimena P; Bodo, Cristian C A; Machiavelli, Leticia I; Quinteros, Alnilan F; Duvilanski, Beatriz H

    2004-11-01

    Cadmium (Cd2+) is a potent toxic metal for both plants and animals. Chronic exposure to low doses of Cd2+ results in damage to several organs. We have previously reported that Cd2+ induces apoptosis in anterior pituitary cells by a caspase- and oxidative stress-dependent mechanism. Nitric oxide (NO) synthesis is affected by Cd2+ in several systems. NO has been shown to be either cytoprotective or cytotoxic in many systems. The aim of this study was to evaluate the possible participation of NO in the cytotoxic effect of Cd2+ on rat anterior pituitary cells. Cell viability was evaluated by mitochondrial dehydrogenase activity assay and confirmed by microscopy, studying nuclear morphology. Here we show that DETA NONOate ((Z)-1-[2 (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate), a long-term NO donor, at concentrations below 0.5 mM, reduces nuclear condensation and fragmentation and reverses the decrease in cellular activity induced by Cd2+. Cd2+, by itself, induced NO synthesis, and inhibition of this synthesis enhanced Cd2+ cytotoxicity. NO also prevented caspase-3 activation and lipidic peroxidation induced by Cd2+. The NO/cGMP pathway does not seem to be involved in the cytoprotective effect of NO. These results indicate that NO has a cytoprotective role in Cd2+ -induced apoptosis, suggesting that endogenous NO could have a physiological role in protecting anterior pituitary cells.

  9. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Jing, Qian; Yue, Jiaqi; Liu, Yang [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Cheng, Zhong [Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Li, Jingyi, E-mail: li--jingyi@hotmail.com [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Song, Haixing [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Li, Guoyu, E-mail: liguoyulisa@163.com [School of Pharmacy, Shihezi University, Shihezi 832003 (China); Liu, Rui, E-mail: liurui_scu@hotmail.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Wang, Jinhui [School of Pharmacy, Shihezi University, Shihezi 832003 (China)

    2016-05-20

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  10. Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

    Science.gov (United States)

    Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

    2015-01-01

    BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

  11. TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

    Science.gov (United States)

    Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

    2008-09-01

    We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

  12. The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

    Science.gov (United States)

    Ma, Long; Liu, Jiangguang

    2014-12-02

    Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this

  13. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats.

    Science.gov (United States)

    Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1μM which peaked at 30min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (pandrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl4) at day 6. Andrographolide pretreatment suppressed CCl4-induced plasma aminotransferase activity and hepatic lipid peroxidation (pandrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The protective effect of Transhinone II A in radiation-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Li Guanghu; Li Zhiping; Xu Yong; Xu Feng; Wang Jin

    2006-01-01

    Objective: To investigate the protective effect and it's possible mechanism of Tanshinone II A in radiation-induced pulmonary fibrosis. Methods: Having the right hemithorax of female Wistar rats irradiated 30 Gy in 10 fractions within 14 days by 6 MV photons, the radiation-induced pulmonary fibrosis animal model was established. In the treatment group, sodium Tanshinone II A sulfonate (15 mg/kg) was given by intraperitoneal injection 1 hour before each fraction of irradiation. Five months after irradiation, the difference of the histopathological changes, the hyckoxyproline content and expression of TGF-β1 between the radiation alone group, tanshinone plus radiation and control group were analyzed by HE stain, Massion stain, immunohistochemical methor and reverse transcriptase polymerase chain reaction(RT-PCR) method. Results: The histopathological comparison revealed the protective effect of Tanshinone II A. The content of hydroxyproline was (21.99±3.96), (38.25± 7.18), (28.94±4.29) μg/g in the control group, radiation alone group and radiation plus Tanshinone II A. The expression of TGF-β1 (mRNA and protein) was reduced by Tanshinone II A. Pathological changes of the pulmonary fibrosis was reduced by Tanshinone II A yet. Conclusions: Our study shows that Tanshinone II A can inhibit radiation-induced pulmonary fibrosis, and the possible mechanism of its may be made possible through down-regulating the expression of TGF-β1 in the irritated lung tissue. (authors)

  15. The neuronal nitric oxide synthase inhibitor, 7-nitroindazole, protects against methamphetamine-induced neurotoxicity in vivo.

    Science.gov (United States)

    Itzhak, Y; Ali, S F

    1996-10-01

    The present study was undertaken to investigate whether the relatively selective neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against methamphetamine (METH)-induced neurotoxicity. Male Swiss Webster mice received the following treatments (i.p.; q 3 h x 3): (a) vehicle/saline, (b) 7-NI (25 mg/kg)/saline, (c) vehicle/METH (5 mg/kg), and (d) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (a) and (b) received two vehicle injections, and groups (c) and (d) received two 7-NI injections (25 mg/kg, each). Administration of vehicle/METH resulted in 68, 44, and 55% decreases in the concentration of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, respectively, and a 48% decrease in the number of [3H]mazindol binding sites in the striatum compared with control values. Treatment with 7-NI (group d) provided full protection against the depletion of dopamine and its metabolites and the loss of dopamine transporter binding sites. Administration of 7-NI/saline (group b) affected neither the tissue concentration of dopamine and its metabolites nor the binding parameters of [3H] mazindol compared with control values. 7-NI had no significant effect on animals' body temperature, and it did not affect METH-induced hyperthermia. These findings indicate a role for nitric oxide in methamphetamine-induced neurotoxicity and also suggest that blockade of NOS may be beneficial for the management of Parkinson's disease.

  16. Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

    Science.gov (United States)

    Cadet, J L; Ordonez, S V; Ordonez, J V

    1997-02-01

    Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

  17. Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

    Science.gov (United States)

    Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

    2015-01-01

    To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

  18. Nitric oxide protects carbon assimilation process of watermelon from boron-induced oxidative injury.

    Science.gov (United States)

    Farag, Mohamed; Najeeb, Ullah; Yang, Jinghua; Hu, Zhongyuan; Fang, Zhang Ming

    2017-02-01

    Nitric oxide (NO) mediates plant response to a variety of abiotic stresses; however, limited information is available on its effect on boron (B)-stressed watermelon plants. The present study investigates the mechanism through which NO protects watermelon seedlings from B deficiency and toxicity stresses. Five days old watermelon seedlings were exposed to B (0, 0.5 and 10 mg L -1 ) alone or with 75 μmole of NO donor sodium nitroprusside (SNP) for 30 days. Both low and high B concentrations in the media altered nutrient accumulation and impaired various physiological processes of watermelon seedlings, leading to a significant reduction in biomass production. The plants exposed to B deficient or toxic concentrations had 66 and 69% lower shoot dry weight, respectively compared with optimum B levels. B toxicity-induced growth inhibition of watermelon seedlings was associated with high B translocation to shoot tissues, which caused lipid membrane peroxidation (12% increase) and chlorophyll destruction (25% reduction). In contrast, B deficiency accelerated generation of reactive oxygen species (ROS), specifically OH -1 and induced cellular oxidative injury. Exogenously applied SNP promoted leaf chlorophyll, photosynthesis and consequently biomass production in B-stressed watermelon seedlings by reducing B accumulation, lipid membrane peroxidation and ROS generation. It also activated antioxidant enzymes such as SOD, POD and APX, and protected the seedlings from ROS-induced cellular burst. Copyright © 2016. Published by Elsevier Masson SAS.

  19. The protective effect of ENA Actimineral resource A on CCl4-induced liver injury in rats.

    Science.gov (United States)

    Hong, Il-Hwa; Ji, Hoon; Hwa, Sung-Yong; Jeong, Won-Il; Jeong, Da-Hee; Do, Sun-Hee; Kim, Ji-Min; Ki, Mi-Ran; Park, Jin-Kyu; Goo, Moon-Jung; Hwang, Ok-Kyung; Hong, Kyung-Sook; Han, Jung-Youn; Chung, Hae-Young; Jeong, Kyu-Shik

    2011-06-01

    ENA Actimineral Resource A (ENA-A) is alkaline water that is composed of refined edible cuttlefish bone and two different species of seaweed, Phymatolithon calcareum and Lithothamnion corallioides. In the present study, ENA-A was investigated as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in rats. Liver injury was induced by either subacute or chronic CCl(4) administration, and the rats had free access to tap water mixed with 0% (control group) or 10% (v/v) ENA-A for 5 or 8 weeks. The results of histological examination and measurement of antioxidant activity showed that the reactive oxygen species production, lipid peroxidation, induction of CYP2E1 were decreased and the antioxidant activity, including glutathione and catalase production, was increased in the ENA-A groups as compared with the control group. On 2-DE gel analysis of the proteomes, 13 differentially expressed proteins were obtained in the ENA-A groups as compared with the control group. Antioxidant proteins, including glutathione S-transferase, kelch-like ECH-associated protein 1, and peroxiredoxin 1, were increased with hepatocyte nuclear factor 3-beta and serum albumin precursor, and kininogen precursor decreased more in the ENA-A groups than compared to the control group. In conclusion, our results suggest that ENA-A does indeed have some protective capabilities against CCl(4)-induced liver injury through its antioxidant function.

  20. Protective effect of thymoquinone against lead-induced hepatic toxicity in rats.

    Science.gov (United States)

    Mabrouk, Aymen; Bel Hadj Salah, Imen; Chaieb, Wafa; Ben Cheikh, Hassen

    2016-06-01

    Lead (Pb) intoxication is a worldwide health problem which frequently affects the liver. This study was carried out to investigate the potential protective effect of thymoquinone (TQ), the major active ingredient of volatile oil of Nigella sativa seeds, against Pb-induced liver damage. Adult male rats were randomized into four groups: Control group received no treatment, Pb group was exposed to 2000 ppm Pb acetate in drinking water, Pb-TQ group was cotreated with Pb plus TQ (5 mg/kg/day, per orally), and TQ group receiving only TQ. All treatments were applied for 5 weeks. Results indicated that Pb exposure increased hepatic Pb content, damaged hepatic histological structure (necrotic foci, hepatic strands disorganization, hypertrophied hepatocytes, cytoplasmic vacuolization, cytoplasmic loss, chromatin condensation, mononuclear cell infiltration, congestion, centrilobular swelling), and changed liver function investigated by plasma biochemical parameters (AST, ALT, ALP, γ-GT, LDH). Pb treatment also decreased total antioxidant status level and increased lipid peroxidation in the liver. Supplementation with TQ remarkably improved the Pb-induced adverse effects without significantly reducing the metal accumulation in the liver. In conclusion, our results indicate, for the first time, a protective effect of TQ against Pb-induced hepatotoxicity and suggest that this component might be clinically useful in Pb intoxication.

  1. Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.

    Science.gov (United States)

    Fuentes-Broto, Lorena; Miana-Mena, Francisco J; Piedrafita, Eduardo; Berzosa, César; Martínez-Ballarín, Enrique; García-Gil, Francisco A; Reiter, Russel J; García, Joaquín J

    2010-08-01

    Cholestasis, encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids. Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent. Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl(3) and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively. In the current study, the rise in MDA + 4-HDA levels induced by TLC was inhibited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes. These results suggest that the indoleamine melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity. Published 2010 Wiley-Liss, Inc.

  2. The Protective Effect of Conditioning on Noise-Induced Hearing Loss Is Frequency-Dependent

    Directory of Open Access Journals (Sweden)

    Akram Pourbakht

    2012-10-01

    Full Text Available We compared the extent of temporary threshold shift (TTS and hair cell loss following high level 4 kHz noise exposure with those preconditioned with moderate level 1 and 4 kHz octave band noise. Fifteen Male albino guinea pigs (300- 350 g in weight were randomly allocated into three groups: those exposed to 4 kHz octave band noise at 102 dB SPL (group 1, n=5; those conditioned with 1 kHz octave band noise at 85 dB SPL, 6 hours per day for 5 days, then exposed to noise (group 2, n=5; those conditioned with 4 kHz octave band noise at 85 dB SPL, then exposed to noise (group 3, n=5. An hour and one week after noise exposure, threshold shifts were evaluated by auditory-evoked brainstem response (ABR and then animals were euthanized for histological evaluation. We found that TTS and cochlear damage caused by noise exposure were significantly reduced by 1 kHz and 4 kHz conditioning (P<0.001. We also showed that 4 kHz protocol attenuates noise- induced TTS but no significant TTS reduction occurred by 1 kHz conditioning. Both protocol protected noise-induced cochlear damage. We concluded that lower tone conditioning could not protect against higher tone temporary noise-induced hearing loss, thus conditioning is a local acting and frequency-dependent phenomenon.

  3. The Protective Role of Curcumin against Gamma-Irradiation Induced Oxidative Stress in Diabetic Mice

    International Nuclear Information System (INIS)

    Nagiub, N.I.; Alkady, M.M.; Emam, W.A.

    2012-01-01

    The present work was aimed to evaluate the radioprotective effect of curcumin (CMN), a yellow pigment of turmeric on γ-radiation (IRR)-induced toxicity in diabetic mice and evaluate the anti-hyper glycemic properties of this compound on streptozotocin (STZ) (65 mg/kg of body weight)-induced diabetes. Serum lipid profiles, glucose level and Tumor necrosis factor-α (TNF-α) were determined. The level of blood glucose was elevated in diabetic animals. Circulatory lipid profiles, and TNF-α were increased significantly. Pretreatment with CMN (200 mg/kg, i.p.) for 5 consecutive days, resulted in a significant decrease in the levels of blood glucose and lipid profiles along with a significant decrease in the levels of TNF-α. The histological results obtained revealed that exposure to ionizing radiation or treatment with STZ caused histopathological damage, in the eye tissue, manifested as congestion in retinal blood capillaries, vacuolation in ganglionic cells and degeneration in nuclear cells of retina. The lens became coagulated, homogenous and oesinophilic. While the cornea showed vacuolations in its epithelium, edema and hyalinosis of substantia propria. Administration of CMN revealed a remarkable protective effect in biochemical and histological levels. Thus, pretreatment with CMN helps in protecting eye tissues against IRR and/or diabetic-induced cellular damage and can be developed in near future as an effective radioprotector during radiotherapy.

  4. Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2016-01-01

    Full Text Available Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ-induced diabetic rat kidney. At the end of the experimental period (28 days, we found that lycopene markedly decreased the malondialdehide (MDA levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and glutathione-S-transferase (GST activities in the kidney of furan-treated rats. In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

  5. Protective effects of Sonchus asper against KBrO3 induced lipid peroxidation in rats.

    Science.gov (United States)

    Khan, Rahmat Ali; Khan, Muhammad Rashid; Sahreen, Sumaira

    2012-11-27

    Sonchus asper is traditionally used in Pakistan for the treatment of reproductive dysfunction and oxidative stress. The present investigation was aimed to evaluate chloroform extract of Sonchus asper (SACE) against potassium bromate-induced reproductive stress in male rats. 20 mg/kg body weight (b.w.) potassium bromate (KBrO3) was induced in 36 rats for four weeks and checked the protective efficacy of SACE at various hormonal imbalances, alteration of antioxidant enzymes, and DNA fragmentation levels. High performance chromatography (HPLC) was used for determination of bioactive constituents responsible. The level of hormonal secretion was significantly altered by potassium bromate. DNA fragmentation%, activity of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and phase II metabolizing enzymes viz; glutathione reductase (GSR), glutathione peroxidase (GSHpx), glutathione-S-tansase (GST) and reduced glutathione (GSH) was decreased while hydrogen per oxide contents and thiobarbituric acid reactive substances (TBARS) were increased with KBrO3 treatment. Treatment with SACE effectively ameliorated the alterations in the biochemical markers; hormonal and molecular levels while HPLC characterization revealed the presence of catechin, kaempferol, rutin and quercetin. Protective effects of Sonchus asper vs. KBrO3 induced lipid peroxidation might be due to bioactive compound present in SACE.

  6. Protective effects of Sonchus asper against KBrO3 induced lipid peroxidation in rats

    Directory of Open Access Journals (Sweden)

    Khan Rahmat Ali

    2012-11-01

    Full Text Available Abstract Background Sonchus asper is traditionally used in Pakistan for the treatment of reproductive dysfunction and oxidative stress. The present investigation was aimed to evaluate chloroform extract of Sonchus asper (SACE against potassium bromate-induced reproductive stress in male rats. Methods 20 mg/kg body weight (b.w. potassium bromate (KBrO3 was induced in 36 rats for four weeks and checked the protective efficacy of SACE at various hormonal imbalances, alteration of antioxidant enzymes, and DNA fragmentation levels. High performance chromatography (HPLC was used for determination of bioactive constituents responsible. Results The level of hormonal secretion was significantly altered by potassium bromate. DNA fragmentation%, activity of antioxidant enzymes; catalase (CAT, peroxidase (POD, superoxide dismutase (SOD and phase II metabolizing enzymes viz; glutathione reductase (GSR, glutathione peroxidase (GSHpx, glutathione-S-tansase (GST and reduced glutathione (GSH was decreased while hydrogen per oxide contents and thiobarbituric acid reactive substances (TBARS were increased with KBrO3 treatment. Treatment with SACE effectively ameliorated the alterations in the biochemical markers; hormonal and molecular levels while HPLC characterization revealed the presence of catechin, kaempferol, rutin and quercetin. Conclusion Protective effects of Sonchus asper vs. KBrO3 induced lipid peroxidation might be due to bioactive compound present in SACE.

  7. Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

    International Nuclear Information System (INIS)

    Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R.

    2006-01-01

    Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, α-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, γ-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects

  8. γ-irradiation-induced mortality: protective effect of protease inhibitors in chickens and mice

    International Nuclear Information System (INIS)

    Palladino, M.A.; Galton, J.E.; Troll, W.; Thorbecke, G.J.

    1982-01-01

    Chickens (Gallus domesticus) were protected from the acute γ-irradiation-induced mortality (within 24 hours) by the proteolytic enzyme inhibitors, soy-bean trypsin inhibitor (SBTI), lima bean inhibitor (LBTI), antipain, α-N-benzoyl-L-arginine ethyl ester HCl (BAEE), trasylol, and leupeptin. Several other enzyme inhibitors, p-tosyl-L-arginine methyl ester HCl (TAME), α-tosyl-lysyl-chloromethyl ketone HCl (TLCK) and epsilon-amino caproic acid (EACA), did not protect. EACA even increased the mortality caused by γ-irradiation. The pattern of protective enzyme inhibitors suggests involvement of a kallikrein-like enzyme. SBTI and antipain also protected against low range lethal γ-irradiation exposures, 690 R in BALB/c and 880 R in SJL/J mice. It is suggested that enhanced vascular permeability, which in chickens is known to be the cause of the irradiation mortality during the first 24 hours, may also contribute to the mortality in mice during the first week after irradiation. (author)

  9. Protective effect of lycopene on high-fat diet-induced cognitive impairment in rats.

    Science.gov (United States)

    Wang, Zhiqiang; Fan, Jin; Wang, Jian; Li, Yuxia; Xiao, Li; Duan, Dan; Wang, Qingsong

    2016-08-03

    A Western diet, high in saturated fats, has been linked to the development of cognitive impairment. Lycopene has recently received considerable attention for its potent protective properties demonstrated in several models of nervous system dysfunction. However, it remains unclear whether lycopene exerts protective effects on cognition. The present study aimed to investigate the protective effects of lycopene on learning and memory impairment and the potential underlying mechanism in rats fed a high-fat diet (HFD). One-month-old male rats were fed different diets for 16 weeks (n=12 per group), including a standard chow diet (CD), a HFD, or a HFD plus lycopene (4mg/kg, oral gavage in the last three weeks). Behavioral testing, including the Morris water maze (MWM), object recognition task (ORT), and anxiety-like behavior in an open field (OF), were assessed at week 16. The dendritic spine density and neuronal density in the hippocampal CA1 subfield were subsequently measured. The results indicate that HFD consumption for 16 weeks significantly impaired spatial memory (Plycopene significantly attenuated learning and memory impairments and prevented the reduction in dendritic spine density (Plycopene helps to protect HFD induced cognitive dysfunction. Copyright © 2016. Published by Elsevier Ireland Ltd.

  10. Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer’s Disease

    Science.gov (United States)

    Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

    2018-01-01

    Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer’s disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD. PMID:29636677

  11. 17β-estradiol and tamoxifen protect mice from manganese-induced dopaminergic neurotoxicity.

    Science.gov (United States)

    Pajarillo, Edward; Johnson, James; Kim, Judong; Karki, Pratap; Son, Deok-Soo; Aschner, Michael; Lee, Eunsook

    2018-03-01

    Chronic exposure to manganese (Mn) causes neurotoxicity, referred to as manganism, with common clinical features of parkinsonism. 17β-estradiol (E2) and tamoxifen (TX), a selective estrogen receptor modulator (SERM), afford neuroprotection in several neurological disorders, including Parkinson's disease (PD). In the present study, we tested if E2 and TX attenuate Mn-induced neurotoxicity in mice, assessing motor deficit and dopaminergic neurodegeneration. We implanted E2 and TX pellets in the back of the neck of ovariectomized C57BL/6 mice two weeks prior to a single injection of Mn into the striatum. One week later, we assessed locomotor activity and molecular mechanisms by immunohistochemistry, real-time quantitative PCR, western blot and enzymatic biochemical analyses. The results showed that both E2 and TX attenuated Mn-induced motor deficits and reversed the Mn-induced loss of dopaminergic neurons in the substantia nigra. At the molecular level, E2 and TX reversed the Mn-induced decrease of (1) glutamate aspartate transporter (GLAST) and glutamate transporter 1 (GLT-1) mRNA and protein levels; (2) transforming growth factor-α (TGF-α) and estrogen receptor-α (ER-α) protein levels; and (3) catalase (CAT) activity and glutathione (GSH) levels, and Mn-increased (1) malondialdehyde (MDA) levels and (2) the Bax/Bcl-2 ratio. These results indicate that E2 and TX afford protection against Mn-induced neurotoxicity by reversing Mn-reduced GLT1/GLAST as well as Mn-induced oxidative stress. Our findings may offer estrogenic agents as potential candidates for the development of therapeutics to treat Mn-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

    Science.gov (United States)

    Zhang, Lili; Lu, Xiangru; Gui, Le; Wu, Yan; Sims, Stephen M; Wang, Guoping; Feng, Qingping

    2016-08-01

    Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. [Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragmatic dysfunction through myogenic regulatory factors].

    Science.gov (United States)

    An, G H; Chen, M; Zhan, W F; Hu, B; Zhang, H X

    2018-02-12

    Objective: To explore the protective effect of electrical stimulation of phrenic nerve on diaphragmatic function during mechanical ventilation. Methods: Forty healthy adult SD rats were randomly divided into 5 groups: blank control group (BC), spontaneous breathing group (SB), electrical stimulation group (ES), mechanical ventilation group (MV), and electrical stimulation and mechanical ventilation group (MS). The rats in each group were treated for 18 h except for the BC group. After treatment, the diaphragm muscle tissue was obtained and the diaphragm contractility including peak-to-peak value(Vpp) and maximum rate of contraction(+ dT/dt max) were measured. Expression of MyoD and myogenin were detected. Results: Except for the ES and the MS groups, there was a significant difference for peak-to-peak value (Vpp) between each 2 groups ( P mechanical ventilation induced diaphragmatic function damage, and therefore plays a protective effect on the diaphragm.

  14. Can VHS virus bypass the protective immunity induced by DNA vaccination in rainbow trout?

    DEFF Research Database (Denmark)

    Sepúlveda, Dagoberto; Lorenzen, Niels

    2016-01-01

    DNA vaccines encoding viral glycoproteins have been very successful for induction of protective immunity against diseases caused by rhabdoviruses in cultured fish species. However, the vaccine concept is based on a single viral gene and since RNA viruses are known to possess high variability...... and adaptation capacity, this work aimed at evaluating whether viral haemorrhagic septicaemia virus (VHSV), an RNA virus and member of Rhabdoviridae family, was able to evade the protective immune response induced by the DNA vaccination of rainbow trout. The experiments comprised repeated passages of a highly...... pathogenic VHSV isolate in a fish cell line in the presence of neutralizing fish serum (in vitro approach), and in rainbow trout immunized with the VHS DNA vaccine (in vivo approach). For the in vitro approach, the virus collected from the last passage (passaged virus) was as sensitive as the parental virus...

  15. DNA vaccination protects mice against Zika virus-induced damage to the testes

    Science.gov (United States)

    Griffin, Bryan D.; Muthumani, Kar; Warner, Bryce M.; Majer, Anna; Hagan, Mable; Audet, Jonathan; Stein, Derek R.; Ranadheera, Charlene; Racine, Trina; De La Vega, Marc-Antoine; Piret, Jocelyne; Kucas, Stephanie; Tran, Kaylie N.; Frost, Kathy L.; De Graff, Christine; Soule, Geoff; Scharikow, Leanne; Scott, Jennifer; McTavish, Gordon; Smid, Valerie; Park, Young K.; Maslow, Joel N.; Sardesai, Niranjan Y.; Kim, J. Joseph; Yao, Xiao-jian; Bello, Alexander; Lindsay, Robbin; Boivin, Guy; Booth, Stephanie A.; Kobasa, Darwyn; Embury-Hyatt, Carissa; Safronetz, David; Weiner, David B.; Kobinger, Gary P.

    2017-01-01

    Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract. PMID:28589934

  16. "Rickettsia amblyommii" induces cross protection against lethal Rocky Mountain spotted fever in a guinea pig model.

    Science.gov (United States)

    Blanton, Lucas S; Mendell, Nicole L; Walker, David H; Bouyer, Donald H

    2014-08-01

    Rocky Mountain spotted fever (RMSF) is a severe illness caused by Rickettsia rickettsii for which there is no available vaccine. We hypothesize that exposure to the highly prevalent, relatively nonpathogenic "Rickettsia amblyommii" protects against R. rickettsii challenge. To test this hypothesis, guinea pigs were inoculated with "R. amblyommii." After inoculation, the animals showed no signs of illness. When later challenged with lethal doses of R. rickettsii, those previously exposed to "R. amblyommii" remained well, whereas unimmunized controls developed severe illness and died. We conclude that "R. amblyommii" induces an immune response that protects from illness and death in the guinea pig model of RMSF. These results provide a basis for exploring the use of low-virulence rickettsiae as a platform to develop live attenuated vaccine candidates to prevent severe rickettsioses.

  17. Potentially induced earthquakes during the early twentieth century in the Los Angeles Basin

    Science.gov (United States)

    Hough, Susan E.; Page, Morgan T.

    2016-01-01

    Recent studies have presented evidence that early to mid‐twentieth‐century earthquakes in Oklahoma and Texas were likely induced by fossil fuel production and/or injection of wastewater (Hough and Page, 2015; Frohlich et al., 2016). Considering seismicity from 1935 onward, Hauksson et al. (2015) concluded that there is no evidence for significant induced activity in the greater Los Angeles region between 1935 and the present. To explore a possible association between earthquakes prior to 1935 and oil and gas production, we first revisit the historical catalog and then review contemporary oil industry activities. Although early industry activities did not induce large numbers of earthquakes, we present evidence for an association between the initial oil boom in the greater Los Angeles area and earthquakes between 1915 and 1932, including the damaging 22 June 1920 Inglewood and 8 July 1929 Whittier earthquakes. We further consider whether the 1933 Mw 6.4 Long Beach earthquake might have been induced, and show some evidence that points to a causative relationship between the earthquake and activities in the Huntington Beach oil field. The hypothesis that the Long Beach earthquake was either induced or triggered by an foreshock cannot be ruled out. Our results suggest that significant earthquakes in southern California during the early twentieth century might have been associated with industry practices that are no longer employed (i.e., production without water reinjection), and do not necessarily imply a high likelihood of induced earthquakes at the present time.

  18. Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats.

    Science.gov (United States)

    El Denshary, Ezzeldeen S; Al-Gahazali, Mohammad A; Mannaa, Fathia A; Salem, Hesham A; Hassan, Nabila S; Abdel-Wahhab, Mosaad A

    2012-11-01

    Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl(4))-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl(4) alone (100 mg/kg b.w) or with CCl(4) after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl(4)-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl(4) induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl(4) plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl(4) after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl(4)-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl(4)-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties. Copyright © 2011 Elsevier GmbH. All rights reserved.

  19. Geraniin Protects High-Fat Diet-Induced Oxidative Stress in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Alexis Panny Y. S. Chung

    2018-03-01

    Full Text Available Geraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro and recently been recognized for its therapeutic potential in metabolic syndrome. This study investigated its antioxidative strength and protective effects on organs in high-fat diet (HFD-induced rodents. Rats were fed HFD for 6 weeks to induce obesity, followed by 10 and 50 mg/kg of geraniin supplementation for 4 weeks to assess its protective potential. The control groups were maintained on standard rat chows and HFD for the same period. At the 10th week, oxidative status was assessed and the pancreas, liver, heart and aorta, kidney, and brain of the Sprague Dawley rats were harvested and subjected to pathological studies. HFD rats demonstrated changes in redox balance; increased protein carbonyl content, decreased levels of superoxide dismutase, glutathione peroxidase, and glutathione reductase with a reduction in the non-enzymatic antioxidant mechanisms and total antioxidant capacity, indicating a higher oxidative stress (OS index. In addition, HFD rats demonstrated significant diet-induced changes particularly in the pancreas. Four-week oral geraniin supplementation, restored the OS observed in the HFD rats. It was able to restore OS biomarkers, serum antioxidants, and the glutathione redox balance (reduced glutathione/oxidized glutathione ratio to levels comparable with that of the control group, particularly at dosage of 50 mg geraniin. Geraniin was not toxic to the HFD rats but exhibited protection against glucotoxicity and lipotoxicity particularly in the pancreas of the obese rodents. It is suggested that geraniin has the pharmaceutical potential to be developed as a supplement to primary drugs in the treatment of obesity and its pathophysiological sequels.

  20. Sirtuin1 and autophagy protect cells from fluoride-induced cell stress

    Science.gov (United States)

    Suzuki, Maiko; Bartlett, John D.

    2014-01-01

    Sirtuin1 (SIRT1) is an (NAD+)-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum stress and oxidative stress. Previously, we reported that fluoride induces endoplasmic reticulum (ER) stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augmented SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50 and 100 ppm) in drinking water for 6 weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. PMID:24296261

  1. Sirtuin1 and autophagy protect cells from fluoride-induced cell stress.

    Science.gov (United States)

    Suzuki, Maiko; Bartlett, John D

    2014-02-01

    Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum (ER) stress and oxidative stress. Previously, we reported that fluoride induces ER-stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augment SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50, 100 and 125ppm) in drinking water for 6weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. 9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons.

    Science.gov (United States)

    Reiner, David J; Yu, Seong-Jin; Shen, Hui; He, Yi; Bae, Eunkyung; Wang, Yun

    2014-04-01

    Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9-Cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has protective effects against damage caused by H(2)O(2) and oxygen-glucose deprivation in vitro as well as infarction and terminal deoxynucleotidyl transferase-mediated dNTP nick-end labeling (TUNEL) labeling in ischemic brain. The purpose of this study was to examine if there was a protective role for 9cRA against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity while increasing TUNEL labeling. These toxicities were significantly reduced by 9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response that activates apoptosis. The interaction of 9cRA and MA in vivo was next examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was given (5 mg/kg, 4×) one day later. Locomotor behavior was measured 2 days after surgery for a period of 48 h. High doses of MA significantly reduced locomotor activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized these changes. Previous studies have shown that 9cRA can induce bone morphogenetic protein-7 (BMP7) expression and that administration of BMP7 attenuates MA toxicity. We demonstrated that MA treatment significantly reduced BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our data suggest that 9cRA has a protective effect against MA-mediated neurodegeneration in dopaminergic neurons via upregulation of BMP.

  3. Medicinal lavender modulates the enteric microbiota to protect against Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    Baker, J; Brown, K; Rajendiran, E; Yip, A; DeCoffe, D; Dai, C; Molcan, E; Chittick, S A; Ghosh, S; Mahmoud, S; Gibson, D L

    2012-10-01

    Inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, consists of immunologically mediated disorders involving the microbiota in the gastrointestinal tract. Lavender oil is a traditional medicine used to relieve many gastrointestinal disorders. The goal of this study was to examine the therapeutic effects of the essential oil obtained from a novel lavender cultivar, Lavandula×intermedia cultivar Okanagan lavender (OLEO), in a mouse model of acute colitis caused by Citrobacter rodentium. In colitic mice, oral gavage with OLEO resulted in less severe disease, including decreased morbidity and mortality, reduced intestinal tissue damage, and decreased infiltration of neutrophils and macrophages, with reduced levels of TNF-α, IFN-γ, IL-22, macrophage inflammatory protein-2α, and inducible nitric oxide synthase expression. This was associated with increased levels of regulatory T cell populations compared with untreated colitic mice. Recently, we demonstrated that the composition of the enteric microbiota affects susceptibility to C. rodentium-induced colitis. Here, we found that oral administration of OLEO induced microbiota enriched with members of the phylum Firmicutes, including segmented filamentous bacteria, which are known to protect against the damaging effects of C. rodentium. Additionally, during infection, OLEO treatment promoted the maintenance of microbiota loads, with specific increases in Firmicutes bacteria and decreases in γ-Proteobacteria. We observed that Firmicutes bacteria were intimately associated with the apical region of the intestinal epithelial cells during infection, suggesting that their protective effect was through contact with the gut wall. Finally, we show that OLEO inhibited C. rodentium growth and adherence to Caco-2 cells, primarily through the activities of 1,8-cineole and borneol. These results indicate that while OLEO promoted Firmicutes populations, it also controlled pathogen load through

  4. Grape (Vitis vinifera) extracts protects against radiation-induced oxidative stress in human erythrocyte (RBC)

    International Nuclear Information System (INIS)

    Ghosh, Subhashis

    2016-01-01

    Ionizing radiation (IR) causes oxidative stress through the overwhelming generation of reactive oxygen species (ROS) in the living cells leading further to the oxidative damage to biomolecules. Grapes (Vitis vinifera) contain several bioactive phytochemicals and are the richest source of antioxidant. In this study, we investigated the radioprotective actions of the grape extracts of two different cultivars, including the Thompson seedless (green) and Kishmish chorni (black) in human erythrocytes. Pretreatment with grape extracts attenuates oxidative stress induced by 4 Gy-radiation in human erythrocytes in vitro. These results suggest that grape extract serve as a potential source of natural antioxidants against the IR-induced oxidative stress and also inhibit apoptosis. Furthermore, the protective action of grape depends on the source of extract (seed, skin or pulp) and type of the cultivars. Effects of grape extracts of different cultivars on protein content, Thiobarbituric acid reactive substances (TBARS) level, reduced glutathione (GSH) content and activities of Catalase, Nitrite, GST, GR in human erythrocytes against -radiation exposure at a dose of 4 Gy are investigated. The grape extracts did not appear to alter the viability of human erythrocytes. Exposure of erythrocytes to the -irradiation at a dose of 4 Gy significantly increased the extent of formation of TBARS, while decreased the level of GSH and activities of CAT, GSSG , GST, GR in the erythrocytes as compared to the non-irradiated control counterparts. This was significantly attenuated by the pretreatment with the grape seed extracts (p<0.001) and significantly with the skin extracts (p<0.05) compared to the ionizing radiation exposed group. Moreover, protection offered by the seed extracts was found significantly better than that was offered by the pulp extract of the same cultivar. In conclusion, our results suggested that the grape extracts significantly attenuated IR induced oxidative stress and

  5. Hydrogen sulfide protects HUVECs against hydrogen peroxide induced mitochondrial dysfunction and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Ya-Dan Wen

    Full Text Available BACKGROUND: Hydrogen sulfide (H₂S has been shown to have cytoprotective effects in models of hypertension, ischemia/reperfusion and Alzheimer's disease. However, little is known about its effects or mechanisms of action in atherosclerosis. Therefore, in the current study we evaluated the pharmacological effects of H₂S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H₂O₂ induced endothelial cells damage. METHODOLOGY AND PRINCIPAL FINDINGS: H₂S, at non-cytotoxic levels, exerts a concentration dependent protective effect in human umbilical vein endothelial cells (HUVECs exposed to H₂O₂. Analysis of ATP synthesis, mitochondrial membrane potential (ΔΨm and cytochrome c release from mitochondria indicated that mitochondrial function was preserved by pretreatment with H₂S. In contrast, in H₂O₂ exposed endothelial cells mitochondria appeared swollen or ruptured. In additional experiments, H₂S was also found to preserve the activities and protein expressions levels of the antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in H₂O₂ exposed cells. ROS and lipid peroxidation, as assessed by measuring H₂DCFDA, dihydroethidium (DHE, diphenyl-l-pyrenylphosphine (DPPP and malonaldehyde (MDA levels, were also inhibited by H₂S treatment. Interestingly, in the current model, D, L-propargylglycine (PAG, a selective inhibitor of cystathionine γ-lyase (CSE, abolished the protective effects of H₂S donors. INNOVATION: This study is the first to show that H₂S can inhibit H₂O₂ mediated mitochondrial dysfunction in human endothelial cells by preserving antioxidant defences. SIGNIFICANCE: H₂S may protect against atherosclerosis by preventing H₂O₂ induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress.

  6. The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration.

    Science.gov (United States)

    Vaczy, A; Reglodi, D; Somoskeoy, T; Kovacs, K; Lokos, E; Szabo, E; Tamas, A; Atlasz, T

    2016-10-01

    A number of studies have proven that pituitary adenylate cyclase activating polypeptide (PACAP) is protective in neurodegenerative diseases. Permanent bilateral common carotid artery occlusion (BCCAO) causes severe degeneration in the rat retina. In our previous studies, protective effects were observed with PACAP1-38, PACAP1-27, and VIP but not with their related peptides, glucagon, or secretin in BCCAO. All three PACAP receptors (PAC1, VPAC1, VPAC2) appear in the retina. Molecular and immunohistochemical analysis demonstrated that the retinoprotective effects are most probably mainly mediated by the PAC1 receptor. The aim of the present study was to investigate the retinoprotective effects of a selective PAC1-receptor agonist maxadilan in BCCAO-induced retinopathy. Wistar rats were used in the experiment. After performing BCCAO, the right eye was treated with intravitreal maxadilan (0.1 or 1 μM), while the left eye was injected with vehicle. Sham-operated rats received the same treatment. Two weeks after the operation, retinas were processed for standard morphometric and molecular analysis. Intravitreal injection of 0.1 or 1 μM maxadilan caused significant protection in the thickness of most retinal layers and the number of cells in the GCL compared to the BCCAO-operated eyes. In addition, 1 μM maxadilan application was more effective than 0.1 μM maxadilan treatment in the ONL, INL, IPL, and the entire retina (OLM-ILM). Maxadilan treatment significantly decreased cytokine expression (CINC-1, IL-1α, and L-selectin) in ischemia. In summary, our histological and molecular analysis showed that maxadilan, a selective PAC1 receptor agonist, has a protective role in BCCAO-induced retinal degeneration, further supporting the role of PAC1 receptor conveying the retinoprotective effects of PACAP.

  7. Management of early pregnancy failure and induced abortion by family medicine educators.

    Science.gov (United States)

    Herbitter, Cara; Bennett, Ariana; Schubert, Finn D; Bennett, Ian M; Gold, Marji

    2013-01-01

    Reproductive health care, including treatment of early pregnancy failure (EPF) and induced abortion, is an integral part of patient-centered care provided by family physicians, but data suggest that comprehensive training is not widely available to family medicine residents. The purpose of this study was to assess EPF and induced abortion management practices and attitudes of family medicine physician educators throughout the United States and Canada. These data were collected as part of a cross-sectional survey conducted by the Council of Academic Family Medicine Educational Research Alliance that was distributed via E-mail to 3152 practicing physician members of Council of Academic Family Medicine organizations. The vast majority of respondents (88.2%) had treated EPF, whereas few respondents (15.3%) had provided induced medication or aspiration abortions. Of those who had treated EPF, most had offered medication management (72.7%), whereas a minority had provided aspiration management (16.4%). Almost all respondents (95%) agreed that EPF management is within the scope of family medicine, and nearly three-quarters (73.2%) agreed that early induced abortion is within the scope of family medicine. Our findings suggest that family physician educators are more experienced with EPF management than elective abortion. Given the overlap of skills needed for provision of these services, there is the potential to increase the number of family physician faculty members providing induced abortions.

  8. Analysis of adenovirus-induced immunity to infection with Listeria monocytogenes: Fading protection coincides with declining CD8 T cell numbers and phenotypic changes.

    Science.gov (United States)

    Jahn, Marie Louise; Steffensen, Maria Abildgaard; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2018-05-11

    Defining correlates of T cell mediated protection is important in order to accelerate the development of efficient T cell based vaccines conferring long-term immunity. Extensive studies have provided important insight regarding the characteristics and functional properties of the effector and memory CD8 T cells induced by viral vector based vaccines. However, long-term protection has been difficult to achieve with T cell inducing vaccines, and the determinants underlying this loss in protection over time are still not fully defined. In this study we analyzed different parameters of the CD8 T cell response as a function of time after vaccination with a human serotype 5 adenovector expressing the glycoprotein (GP) of LCMV tethered to the MHC class II-associated invariant chain. Using this vector we have previously found that CD8 T cells mediate protection from challenge with GP-expressing Listeria monocytogenes at 60 days post vaccination, but only little protection after further 60 days, and we now confirm this observation. A comparison of vaccine-primed CD8 T cells early and late after vaccination revealed a minor decline in the overall numbers of antigen specific memory CD8 T cells during this interval. More importantly, we also observed phenotypic changes over time with a distinct decline in the frequency and number of KLRG1 + CD8 T cells, and, notably, adoptive transfer studies confirmed that memory CD8 T cells expressing KLRG1 are central to protection from systemic L. monocytogenes infection. Together these findings imply that multiple factors including changes in memory T cell numbers and phenotypic composition over time influence the longevity of CD8 T-cell mediated protection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Hypothalamic neuronal toll-like receptor 2 protects against age-induced obesity

    OpenAIRE

    Shechter, Ravid; London, Anat; Kuperman, Yael; Ronen, Ayal; Rolls, Asya; Chen, Alon; Schwartz, Michal

    2013-01-01

    Toll-like receptors (TLRs) are traditionally associated with immune-mediated host defense. Here, we ascribe a novel extra-immune, hypothalamic-associated function to TLR2, a TLR-family member known to recognize lipid components, in the protection against obesity. We found that TLR2-deficient mice exhibited mature-onset obesity and susceptibility to high-fat diet (HFD)-induced weight gain, via modulation of food intake. Age-related obesity was still evident in chimeric mice, carrying comparabl...

  10. Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.

    Science.gov (United States)

    Li, Y; King, M A; Grimes, J; Smith, N; de Fiebre, C M; Meyer, E M

    1999-01-16

    Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity. Copyright 1999 Elsevier Science B.V.

  11. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yongke Lu

    2015-10-01

    Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

  12. Protective Effect of Rosemary (Rosmarinus Officinalis Extract on Naphthalene Induced Nephrotoxicity in Adult Male Albino Rat

    Directory of Open Access Journals (Sweden)

    Neveen M. El-Sherif

    2015-02-01

    Full Text Available Background: Naphthalene (NA is a common environmental contaminant and is abundant in tobacco smoke. Rosemary (Rosmarinus officinalis is a herb commonly used as a spice and flavoring agents in food processing and is useful in the treatment of many diseases. Aim of the work: To study the nephrotoxicity of NA and to evaluate the possible protective role of rosemary extract in adult male albino rat. Materials and Methods: 25 animals were divided into three groups: Group I (Control group, Group II (NA treated group received NA at a dose of 200 mg/kg/day dissolved in 5 ml/kg corn oil orally by gastric tube, Group III (protected group received rosemary extract (10 ml/kg/day followed after 60 min by NA at the same previous dose orally by gastric tube. The experiment lasted 30 days. The following parameters were studied: Biochemical assessment of renal function, histological, immunohistochemical, morphometric studies and statistical analysis of the results. Results: NA treatment resulted in a highly significant increase in the mean values of serum urea and creatinine. NA induced histological changes in the form of glomerular congestion. Some glomeruli demonstrated marked mesangial expansion and hence that Bowman's spaces were almost completely obliterated. Shrinkage of renal glomeruli with widening of Bowman's spaces could also be seen. Focal tubular dilatation with appearance of casts inside the tubules was observed. Congested peritubular blood vessels and interstitial hemorrhage were also seen. The medullary region demonstrated vascular congestion and fibrosis. Focal cellular infiltration was presented in the interstitium. The renal cortex of NA treated rats showed a noticeable down regulation in alkaline phosphatase positive immunoreactive cells in some proximal convoluted tubules. NA induced up regulation of positive immunoreaction for inducible nitric oxide synthase in the proximal and distal convoluted tubules as well as in the collecting tubules

  13. Long-wave UVA offers partial protection against UVB-induced

    DEFF Research Database (Denmark)

    Skov, L.; Villadsen, L.; Ersbøll, Bjarne Kjær

    2000-01-01

    Ultraviolet-B (UVB, 280–320 nm) interferes with the generation of cell-mediated immunity to contact allergens applied epicutaneously on the irradiated site. To investigate whether pretreatment with UVA-1 (340–400 nm) protects against the UVB-induced immune suppression we sensitized human volunteers...... with diphenylcyclopropenone (DPCP) on normal buttock skin (n=12), on UVB-irradiated buttock skin (n=21), on buttock skin pretreated with UVA-1 (n=12), and on buttock skin pretreated with UVA-1 and thereafter irradiated with UVB (n=22). Sensitization on UVB-irradiated skin reduced the immunization rate to DPCP compared...

  14. Protecting a full-scale Nb3Sn magnet with CLIQ, the new coupling-loss-induced quench system

    NARCIS (Netherlands)

    Ravaioli, Emanuele; Bajas, H.; Datskov, V.I.; Desbiolles, V.; Feuvrier, J.; Kirby, G.; Maciejewski, M.; Sabbi, G.; ten Kate, Herman H.J.; Verweij, A.P.

    2015-01-01

    A new protection system for superconducting magnets called coupling-loss induced quench system (CLIQ) has been recently developed at CERN. Recent tests on Nb-Ti coils have shown that CLIQ is a valid, efficient, and promising method for the protection of high-magnetic-field superconducting magnets.

  15. Protective effect of taurine on the light-induced disruption of isolated frog rod outer segments

    International Nuclear Information System (INIS)

    Pasantes-Morales, H.; Ademe, R.M.; Quesada, O.

    1981-01-01

    Isolated frog rod outer segments (ROS) incubated in a Krebs-bicarbonate medium, and illuminated for 2 h, show a profound alteration in their structure. This is characterized by distention of discs, vesiculation, and a marked swelling. The light-induced ROS disruption requires the presence of bicarbonate and sodium chloride. Replacement of bicarbonate by TRIS or HEPES protects ROS structure. Also, substitution of sodium chloride by sucrose or choline chloride maintains unaltered the ROS structure. Deletion of calcium, magnesium, or phosphate does not modify the effect produced by illumination. An increased accumulation of labeled bicarbonate and tritiated water is observed in illuminated ROS, as compared with controls in the dark. The presence of taurine, GABA, or glycine, at concentrations of 5-25 mM, effectively counteracts the light-induced ROS disruption. Taurine (25 mM) reduces labeled bicarbonate and tritiated water levels to those observed in the dark incubated ROS

  16. Schisandrin B protects against solar irradiation-induced oxidative injury in BJ human fibroblasts.

    Science.gov (United States)

    Chiu, Po Yee; Lam, Philip Y; Yan, Chung Wai; Ko, Kam Ming

    2011-06-01

    The effects of schisandrin B (Sch B) and its analogs on solar irradiation-induced oxidative injury were examined in BJ human fibroblasts. Sch B and schisandrin C (Sch C) increased cellular reduced glutathione (GSH) level and protected against solar irradiation-induced oxidative injury. The photoprotection was paralleled by decreases in the elastases-type protease activity and matrix-metalloproteinases-1 expression in solar-irradiated fibroblasts. The cytochrome P-450-mediated metabolism of Sch B or Sch C caused ROS production. The results suggest that by virtue of its pro-oxidant action and the subsequent glutathione antioxidant response, Sch B or Sch C may offer the prospect of preventing skin photo-aging. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes.

    Science.gov (United States)

    Zapolska-Downar, Danuta; Zapolski-Downar, Andrzej; Naruszewicz, Marek; Siennicka, Aldona; Krasnodebska, Barbara; Kołdziej, Blanka

    2002-11-01

    It is currently believed that oxidative stress and inflammation play a significant role in atherogenesis. Artichoke extract exhibits hypolipemic properties and contains numerous active substances with antioxidant properties in vitro. We have studied the influence of aqueous and ethanolic extracts from artichoke on intracellular oxidative stress stimulated by inflammatory mediators (TNFalpha and LPS) and ox-LDL in endothelial cells and monocytes. Oxidative stress which reflects the intracellular production of reactive oxygen species (ROS) was followed by measuring the oxidation of 2', 7'-dichlorofluorescin (DCFH) to 2', 7'-dichlorofluorescein (DCF). Agueous and ethanolic extracts from artichoke were found to inhibit basal and stimulated ROS production in endothelial cells and monocytes in dose dependent manner. In endothelial cells, the ethanolic extract (50 microg/ml) reduced ox-LDL-induced intracellular ROS production by 60% (partichoke extracts have marked protective properties against oxidative stress induced by inflammatory mediators and ox-LDL in cultured endothelial cells and monocytes.

  18. Protective effects of nelumbo nucifera against {gamma}-irradiation-induced lipid peroxidation in mice urine

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Il Yun; Park, Yong Dae; Jin, Caang Hyun; Choi, Dae Seong [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Lee, Hyo Jung [Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of)

    2009-12-15

    The radioprotective effect of isoquercitrin-abundant fraction (IAF) of N. nucifera Gaertn. Ieaf extract against {gamma}-irradiation-induced oxidative stress was evaluated by the lipid peroxidation-derived aldehydes (LPDAs) as a marker for oxidative risk in mice urine, and the DNA damage using comet assay in RAW 264.7 cells. Mice that were treated with IAF (50 mg/kg) and {gamma}-irradiation showed considerably decreased LPDA levels relative to those that had received {gamma}-irradiation alone. Furthermore, pretreatment with IAF resulted in a significant decrease in the amount of DNA damage in cells. It is demonstrated that pretreatment with IAF of N. nucifera Gaertn. gives protection against irradiation-induced cellular damage.

  19. Protective Effect of Ischemic Postconditioning against Ischemia Reperfusion-Induced Myocardium Oxidative Injury in IR Rats

    Directory of Open Access Journals (Sweden)

    Jiangwei Ma

    2012-03-01

    Full Text Available Brief episodes of myocardial ischemia-reperfusion (IR employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK, lactate dehydrogenase (LDH and aspartate transaminase (AST activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px and glutathione reductase (GR activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

  20. Tn5-induced pBS286 plasmid mutations blocking early stages of napthalene oxidation

    International Nuclear Information System (INIS)

    Kosheleva, I.A.; Tsoi, T.V.; Ivashina, T.V.; Selifonov, S.A.; Starovoitov, I.I.; Boronin, A.M.

    1988-01-01

    The authors present data on the further analysis of the structural and functional organization of the nah region of plasmid pBS286 controlling the constitutive oxidation of naphthalene by Pseudomonas putida cells. They have studied Tn5-induced mutations blocking early stages of naphthalene oxidation. They present and discuss data providing evidence that, in contrast to plasmid NAH7, the mechanism of regulation of the nahl operon of plasmid NPL-1, the parent plasmid of plasmid pBS286, with inducible synthesis of naphthalene dioxygenase can include elements of a negative control with participation of the regulatory locus R, located proximal to the structural nah genes and closely linked to or overlapped by the inverted control DNA segment (4.2 kb). They also present data on the possibility of regulation of the activity of the catechol-splitting meta-pathway genes with the participation of products of early stages of naphthalene oxidation

  1. Inducible protective processes in animal systems XV: Hyperthermia enhances the Ethyl methanesulfonate induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus

    Directory of Open Access Journals (Sweden)

    R. Venu

    2016-04-01

    Conclusion: There is a protection against EMS induced anomalies by hyperthermia in in vivo P. pictus. As far as our knowledge is concerned, this is the first report to demonstrate that hyperthermia enhances the EMS induced adaptive response in in vivo meiotic cells.

  2. Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways.

    Science.gov (United States)

    Zhao, Wenwen; Wu, Chuanhong; Li, Shaojing; Chen, Xiuping

    2016-12-01

    Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKβ, p-IκBα, p-p65 expression, and p-IκBα-IKKβ interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKβ pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Haw-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Li, Chien-Chun [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Ai-Hsuan; Huang, Yu-Ju [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Tsu-Shing [Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China); Yao, Hsien-Tsung [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

  4. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    International Nuclear Information System (INIS)

    Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

    2014-01-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl 4 ) at day 6. Andrographolide pretreatment suppressed CCl 4 -induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense in

  5. Ipomoea aquatica Extract Shows Protective Action Against Thioacetamide-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    A. Hamid A. Hadi

    2012-05-01

    Full Text Available In the Indian system of traditional medicine (Ayurveda it is recommended to consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the protective effects of ethanol extract of I. aquatica against liver damage were evaluated in thioacetamide (TAA-induced chronic hepatotoxicity in rats. There was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD rats were orally fed with I. aquatica (250 and 500 mg/kg for two months along with administration of TAA (i.p injection 200 mg/kg three times a week for two months. The results showed that the treatment of I. aquatica significantly lowered the TAA-induced serum levels of hepatic enzyme markers (ALP, ALT, AST, protein, albumin, bilirubin and prothrombin time. The hepatic content of activities and expressions SOD and CAT that were reduced by TAA were brought back to control levels by the plant extract supplement. Meanwhile, the rise in MDA level in the TAA receiving groups also were significantly reduced by I. aquatica treatment. Histopathology of hepatic tissues by H&E and Masson trichrome stains displayed that I. aquatica has reduced the incidence of liver lesions, including hepatic cells cloudy swelling, infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by TAA in rats. Therefore, the results of this study show that the protective effect of I. aquatica in TAA-induced liver damage might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects. Moreover, it confirms a scientific basis for the traditional use of I. aquatica for the treatment of liver disorders.

  6. Protective effects of the Morus alba L. leaf extracts on cisplatin-induced nephrotoxicity in rat

    Science.gov (United States)

    Nematbakhsh, M; Hajhashemi, V; Ghannadi, A; Talebi, A; Nikahd, M

    2013-01-01

    Cisplatin (CP) as an important anti-tumor drug causes nephrotoxicity mainly by oxidative stress and renin-angiotensin system (RAS). Since flavonoids have high antioxidant activity and probable role in the inhibition of RAS, this study was designed to investigate the protective effect of hydroalcoholic extract and flavonoid fraction of Morus alba leaves on cisplatin-induced nephrotoxicity in rat. Extracts of Morus alba leaves were prepared and analyzed Phytochemically. Male rats (160-200 g) were used in this study (n=7-9). Normal group received 0.2 ml normal saline intraperitoneally (i.p.) once daily for ten days. Control animals received CP on the third day and saline in the remaining days. Other groups received either hydroalcoholic extract (200, 400 and 600 mg/kg, i.p.) or flavonoid fraction (50, 100 and 200 mg/kg, i.p.) for two days before CP administration and thereafter until tenth day. Serum concentrations of blood urea nitrogen (BUN), creatinine (Cr) and nitric oxide were measured using standard methods. Also left kidneys were prepared for pathological study. The serum levels of BUN and Cr increased in animals received CP. Hydroalcoholic extract was ineffective in reversing these alterations but flavonoid fraction (50 and 100 mg/kg) significantly inhibited CP-induced increases of BUN and Cr. None of the treatments could affect serum concentration of nitric oxide. Flavonoid fraction could also prevent CP-induced pathological damage of the kidney. It seems that concurrent use of flavonoid fraction of Morus alba with CP can protect kidneys from CP-induced nephrotoxicity. PMID:24019816

  7. Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling.

    Science.gov (United States)

    Zhang, Min; Mongue-Din, Heloise; Martin, Daniel; Catibog, Norman; Smyrnias, Ioannis; Zhang, Xiaohong; Yu, Bin; Wang, Minshu; Brandes, Ralf P; Schröder, Katrin; Shah, Ajay M

    2018-03-01

    NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4. Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization. Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density. © The Author 2017 Published by Oxford University Press on behalf of the European Society of Cardiology.

  8. Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice.

    Science.gov (United States)

    Yadav, Umesh C S; Shoeb, Mohammed; Srivastava, Satish K; Ramana, Kota V

    2011-10-17

    To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ∼2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

  9. Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

    2018-06-15

    Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Protective effects of plant seed extracts against amyloid β-induced neurotoxicity in cultured hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Yoshinori Okada

    2013-01-01

    Full Text Available Aim: Alzheimer′s disease (AD is characterized by large deposits of amyloid β (Aβ peptide. Aβ is known to increase reactive oxygen species (ROS production in neurons, leading to cell death. In this study, we screened 15 plant seeds′ aqueous extracts (PSAE for inhibitory effects on Aβ (25-35-induced cell death using hippocampus neurons (HIPN. Materials and Methods: Fifteen chosen plants were nine medical herbs (Japanese honeywort, luffa, rapeseed, Chinese colza, potherb mustard, Japanese radish, bitter melon, red shiso, corn, and kaiware radish and six general commercial plants (common bean, komatsuna, Qing geng cai, bell pepper, kale, and lettuce. PSAE were measured for total phenolic content (TPC with the Folin-Ciocalteu method, and the 2-diphenyl-1-picryl-hydrazyl (DPPH radical scavenging effect of each seed extract was measured. To find a protectant against Aβ-induced oxidative stress, we screened 15 PSAE using a 2′, 7′-dichlorofluorescein diacetate assay. To further unravel the anti-inflammatory effects of PSAE on Aβ-induced inflammation, PSAE were added to HIPN. The neuroprotective effects of the PSAE were evaluated by Cell Counting Kit-8 assay, measuring the cell viability in Aβ-induced HIPN. Results: TPC of 15 PSAE was in the range of 0.024-1.96 mg of chlorogenic acid equivalents/gram. The aqueous extracts showed antioxidant activities. Furthermore, intracellular ROS accumulation resulting from Aβ treatment was reduced when cells were treated with some PSAE. Kale, bitter melon, kaiware radish, red shiso, and corn inhibited tumor necrosis factor-alpha secretion by the Aβ-stimulated neurons and all samples except Japanese honeywort showed enhancement of cell survival. Conclusion: From these results, we suggest that some plant seed extracts offer protection against Aβ-mediated cell death.

  11. Protective effects of plant seed extracts against amyloid β-induced neurotoxicity in cultured hippocampal neurons.

    Science.gov (United States)

    Okada, Yoshinori; Okada, Mizue

    2013-04-01

    Alzheimer's disease (AD) is character