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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.
Biochem Cell Biol. 2015 Jun; 93(3):210-26.BC

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+Show Affiliations

Department of Zoology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Retracted Publication

Language

eng

PubMed ID

25719599

Citation

Nazima, Bashir, et al. "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." Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire, vol. 93, no. 3, 2015, pp. 210-26.
Nazima B, Manoharan V, Miltonprabu S. 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. Biochem Cell Biol. 2015;93(3):210-26.
Nazima, B., Manoharan, V., & Miltonprabu, S. (2015). 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. Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire, 93(3), 210-26. https://doi.org/10.1139/bcb-2014-0114
Nazima B, Manoharan V, Miltonprabu S. 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. Biochem Cell Biol. 2015;93(3):210-26. PubMed PMID: 25719599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Nazima,Bashir, AU - Manoharan,Vaihundam, AU - Miltonprabu,Selvaraj, Y1 - 2014/12/11/ PY - 2015/2/27/entrez PY - 2015/2/27/pubmed PY - 2016/2/24/medline KW - ERO KW - Nrf2 KW - ROS KW - apoptose KW - apoptosis KW - cadmium KW - grape seed proanthocyanidins KW - inflammation KW - nephrotoxicity KW - néphrotoxicité KW - oxidative stress KW - proanthocyanidines de pépins de raisin KW - rats KW - stress oxydant SP - 210 EP - 26 JF - Biochemistry and cell biology = Biochimie et biologie cellulaire JO - Biochem Cell Biol VL - 93 IS - 3 N2 - 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. SN - 1208-6002 UR - https://www.unboundmedicine.com/medline/citation/25719599/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_ DB - PRIME DP - Unbound Medicine ER -