title: Resveratrol abrogates alcohol-induced cognitive deficits by attenuating oxidative-nitrosative stress and inflammatory cascade in the adult rat brain.
abstract: Chronic alcohol intake is known to induce permanent cognitive deficits along with enhanced oxidative-nitrosative stress and activation of neuroinflammatory cascade. In the present study, we investigated the protective effect of resveratrol, a natural polyphenolic phytoalexin against chronic alcohol-induced cognitive dysfunction and neuroiflammatory cascade in the brain of adult rats chronically administered ethanol. Male Wistar rats were adminstered ethanol (10g/kg; oral gavage) for ten weeks and treated with resveratrol (5, 10 and 20mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappa β and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with resveratrol significantly and dose-dependently prevented all the behavioral, biochemical and molecular deficits. Correlatively, the results of the present study revealed that treatment with resveratrol significantly prevented cognitive deficits induced by chronic ethanol exposure not only by modulating oxido-nitrosative stress but also by attenuating the enhanced levels of pro-inflammatory cytokines (TNF-α and IL-1β), NF-kβ and caspase-3 in different brain regions of ethanol treated rats. Therefore, mechanism underlying the neuroprotective effects of resveratrol observed in our study may be due to its antioxidant, anti-inflammatory and neuromodulating activities.
authors: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh 160 014, India.
authors: Vinod
authors: V
authors: Tiwari
authors: Kanwaljit
authors: K
authors: Chopra
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D002374:Catalase / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D004660:Encephalitis / Q000517:prevention & control*; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002492:Central Nervous System Depressants; D053583:Interleukin-1beta; D016328:NF-kappa B; D009573:Nitrites; D026361:Reactive Nitrogen Species; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D002374:Catalase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D005978:Glutathione; D000077185:Resveratrol