title: Epigallocatechin-3-gallate activates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats.
abstract: OBJECTIVE
  Cisplatin-induced nephrotoxicity is associated with increased oxidative stress and inflammatory cytokines in the kidney. Epigallocatechin-3-gallate (EGCG) has anti-oxidant, anti-inflammatory, and anti-tumorigenic properties. In this study, we investigated the effects of EGCG on cisplatin-induced nephrotoxicity and potential mechanisms by which it enhances antioxidant activities and resolves inflammation after EGCG treatment during cisplatin-induced nephrotoxicity.
  
  
  METHODS
  Twenty-eight rats were divided into four groups as control (group 1; no treatment; n=7), EGCG (group 2; n=7), cisplatin (group 3; n=7) or cisplatin and EGCG (group 4; n=7). After 2 days of EGCG treatment at a dose of l00 mg/kg BW, rats were treated with a single i.p. injection of cisplatin (7 mg/kg BW). On day 12 (10days after the cisplatin treatment), all rats were sacrificed by cervical dislocation. The level of protein was examined by Western blotting.
  
  
  RESULTS
  Cisplatin caused a significant decrease in the expression nuclear levels of NF-E2-related factor-2 (Nrf2), heme oxygenase-1(HO-1), and an increase in the levels of nuclear factor-kappa B (NF-kappaB p65) and 4-hydroxynonenal (HNE) an oxidative stress marker. EGCG supplementation significantly improved the changes associated with cisplatin nephrotoxicity by increasing levels of Nrf-2 and HO-1, and decreasing levels of NF-kappaB and HNE. Renal activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione were significantly lower in cisplatin-treated rats compared with control rats, and EGCG treatment significantly increased the activities of antioxidant enzymes and glutathione (P<0.001).
  
  
  CONCLUSIONS
  The results suggest that Nrf2/HO-1 signaling pathway may be the primary target for prevention of cisplatin-induced nephrotoxicity by EGCG, and that reduces it inflammation by inhibiting NF-kappaB.
authors.affiliation: Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey. nsahinkm@yahoo.com
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Hasan
authors.initials: H
authors.lastname: Gencoglu
authors.forename: Ayhan
authors.initials: A
authors.lastname: Dogukan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Timurkan
authors.forename: Nurhan
authors.initials: N
authors.lastname: Sahin
authors.forename: Abdullah
authors.initials: A
authors.lastname: Aslan
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013662:Tea / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000970:Antineoplastic Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D002374:Catalase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D002945:Cisplatin