title: Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation.
abstract: TNF-alpha and NF-kappaB play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic cells, curcumin is shown to antagonize TNF-alpha-elicited NF-kappaB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared with enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague-Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin-treated (curcumin), and enalapril-treated (enalapril) groups. Sham-operated animals served as a control. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared with the control, the Nx animals had significantly higher plasma and kidney TNF-alpha, which was associated with NF-kappaB activation and macrophage infiltration in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARgamma) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF-alpha. Curcumin dose dependently antagonized the TNF-alpha-mediated decrease in PPARgamma and blocked transactivation of NF-kappaB and repression of PPARgamma, indicating that the anti-inflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.
authors.affiliation: Department of Internal Medicine/Nephrology, Sanger Hall, Rm. 8-059, Virginia Commonwealth Univ., 1101 E. Marshall St., Richmond, VA 23298, USA. ssghosh@hsc.vcu.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Ghosh
authors.forename: H D
authors.initials: HD
authors.lastname: Massey
authors.forename: R
authors.initials: R
authors.lastname: Krieg
authors.forename: Z A
authors.initials: ZA
authors.lastname: Fazelbhoy
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: D A
authors.initials: DA
authors.lastname: Sica
authors.forename: I
authors.initials: I
authors.lastname: Fakhry
authors.forename: T W B
authors.initials: TW
authors.lastname: Gehr
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009392:Nephrectomy; D009393:Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D004656:Enalapril; D003404:Creatinine; D003474:Curcumin