Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract.

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dc.contributor.authorBagchi, Debasisen_US
dc.contributor.authorRay, Sidhartha Den_US
dc.contributor.authorBagchi, Manashien_US
dc.contributor.authorPreuss, Harry Gen_US
dc.contributor.authorStohs, Sidney Jen_US
dc.date.accessioned2009-05-28T16:32:45Z
dc.date.available2009-05-28T16:32:45Z
dc.date.issued2002-06-18en_US
dc.description.abstractTo understand the bioavailability and mechanistic pathways of cytoprotection by IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) a series of in vitro and in vivo studies were conducted. Comparative protective abilities of GSPE, and vitamins C and E, singly and in combination, were assessed against smokeless tobacco extract (STE)-induced oxidative stress, DNA fragmentation and apoptotic cell death in a primary culture of normal human oral keratinocytes. GSPE protected against STE-induced oxidative stress, DNA damage and apoptotic cell death, and provided better protection as compared to vitamins C and E, singly and in combination. The bioavailability and protective ability of GSPE were examined against acetaminophen (AP)-induced hepato- and nephrotoxicity, amiodarone (AM)-induced lung toxicity, doxorubicin (DX)-induced cardiotoxicity and dimethylnitrosamine (DM)-induced spleenotoxicity in mice. GSPE-fed animals were compared with GSPE-untreated mice to evaluate the protective ability of GSPE against these structurally diverse drugs/chemicals. Serum chemistry changes, histopathology and DNA damage were evaluated. Results indicate that GSPE preexposure prior to the drugs/chemicals such as AP, AM, DX or DM treatment, provided near complete protection in terms of serum chemistry changes and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced in GSPE-fed animals. Histopathological examination of multiple target organs provided similar data. The results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against structurally diverse drug- and chemical-induced toxic assaults. Further, these studies exhibited a series of mechanistic information including free radical scavenging ability, anti-endonucleolytic activity, cytochrome P450 2E1 inhibitory activity, anti-necrotic, anti-apoptotic and anti-carcinogenic activities, modulatory effects on antioxidative and apoptotic regulatory genes such as Bcl2, c-myc and p53, which may be responsible for the novel chemoprotective properties exhibited by GSPE.en_US
dc.description.affiliationCreighton University School of Pharmacy & Allied Health Professions, Omaha, NE 68178, USA. debsis@creighton.eduen_US
dc.identifier.citationBagchi D, Ray SD, Bagchi M, Preuss HG, Stohs SJ. Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract. Indian Journal of Experimental Biology. 2002 Jun; 40(6): 717-26en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/63367
dc.language.isoengen_US
dc.source.urihttps://www.niscair.res.in/ScienceCommunication/ResearchJournals/rejour/ijeb/ijeb0.aspen_US
dc.subject.meshAcetaminophen --administration & dosageen_US
dc.subject.meshAdministration, Oralen_US
dc.subject.meshAlanine Transaminase --blooden_US
dc.subject.meshAmiodarone --administration & dosageen_US
dc.subject.meshAnalgesics, Non-Narcotic --administration & dosageen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Agents --administration & dosageen_US
dc.subject.meshAntioxidants --pharmacologyen_US
dc.subject.meshApoptosis --drug effectsen_US
dc.subject.meshBlood Urea Nitrogenen_US
dc.subject.meshCell Cycle --drug effectsen_US
dc.subject.meshCreatine Kinase --blooden_US
dc.subject.meshDNA Damage --drug effectsen_US
dc.subject.meshDimethylnitrosamine --administration & dosageen_US
dc.subject.meshDoxorubicin --administration & dosageen_US
dc.subject.meshDrug Toxicity --prevention & controlen_US
dc.subject.meshFree Radical Scavengers --administration & dosageen_US
dc.subject.meshHeart Diseases --chemically induceden_US
dc.subject.meshHumansen_US
dc.subject.meshInjections, Intraperitonealen_US
dc.subject.meshKeratinocytes --drug effectsen_US
dc.subject.meshKidney Diseases --chemically induceden_US
dc.subject.meshLipid Peroxidation --drug effectsen_US
dc.subject.meshLung Diseases --chemically induceden_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred ICRen_US
dc.subject.meshNecrosisen_US
dc.subject.meshOxidation-Reductionen_US
dc.subject.meshPlant Extracts --pharmacologyen_US
dc.subject.meshProanthocyanidinsen_US
dc.subject.meshSpleen --injuriesen_US
dc.subject.meshTobacco, Smokeless --adverse effectsen_US
dc.subject.meshVasodilator Agents --administration & dosageen_US
dc.titleMechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract.en_US
dc.typeComparative Studyen_US
dc.typeIn Vitroen_US
dc.typeJournal Articleen_US
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