title: Grape seed proanthocyanidins ameliorates cadmium-induced renal injury and oxidative stress in experimental rats through the up-regulation of nuclear related factor 2 and antioxidant responsive elements.
abstract: Cadmium (Cd) preferentially accumulates in the kidney, the major target for Cd-related toxicity. Cd-induced reactive oxygen species (ROS) have been considered crucial mediators for renal injury. The biologically significant ionic form of cadmium (Cd(+)) binds to many bio-molecules, and these interactions underlie the toxicity mechanisms of Cd. The present study was hypothesized to explore the protective effect of grape seed proanthocyanidins (GSP) on Cd-induced renal toxicity and to elucidate the potential mechanism. Male Wistar rats were treated with Cd as cadmium chloride (CdCl2, 5 mg·kg(-1) bw, orally) and orally pre-administered with GSP (100 mg·kg(-1) bw) 90 min before Cd intoxication for 4 weeks to evaluate renal damage of Cd and antioxidant potential of GSP. Serum renal function parameters (blood urea nitrogen and creatinine) levels in serum and urine, renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic, and non-enzymatic antioxidants), inflammatory (NF-κB p65, NO, TNF-α, IL-6), apoptotic (caspase-3, caspase-9, Bax, Bcl-2), membrane bound ATPases, and Nrf2 (HO-1, keap1, γ-GCS, and μ-GST) markers were evaluated in Cd-treated rats. Pretreatment with GSP revealed a significant improvement in renal oxidative stress markers in kidneys of Cd-treated rats. In addition, GSP treatment decreases the amount of iNOS, NF-κB, TNF-α, caspase-3, and Bax and increases the levels Bcl-2 protein expression. Similarly, mRNA and protein analyses substantiated that GSP treatment notably normalizes the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in the Cd-treated rats. Histopathological and ultra-structural observations also demonstrated that GSP effectively protects the kidney from Cd-induced oxidative damage. These findings suggest that GSP ameliorates renal dysfunction and oxidative stress through the activation of Nrf2 pathway in Cd-intoxicated rats.
authors.affiliation: Department of Zoology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
authors.forename: Bashir
authors.initials: B
authors.lastname: Nazima
authors.forename: Vaihundam
authors.initials: V
authors.lastname: Manoharan
authors.forename: Selvaraj
authors.initials: S
authors.lastname: Miltonprabu
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D056604:Grape Seed Extract / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D044945:Proanthocyanidins / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D044945:Proanthocyanidins; D020011:Protective Agents; D002104:Cadmium; D000251:Adenosine Triphosphatases
keywords: ERO; Nrf2; ROS; apoptose; apoptosis; cadmium; grape seed proanthocyanidins; inflammation; nephrotoxicity; néphrotoxicité; oxidative stress; proanthocyanidines de pépins de raisin; rats; stress oxydant