title: Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway.
abstract: We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium [Cr(VI)] compound potassium dichromate (K(2)Cr(2)O(7)) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400 mg/kg bw 10 days before and 2 days after K(2)Cr(2)O(7) injection), (2) pretreatment (400 mg/kg bw for 10 days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400 mg/kg bw 2 days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48 h later after a single K(2)Cr(2)O(7) injection (15 mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysfunction, histological damage, oxidant stress, and the decrease in antioxidant enzyme activity both in kidney tissue and in mitochondria. Curcumin pretreatment attenuated K(2)Cr(2)O(7)-induced mitochondrial dysfunction (alterations in oxygen consumption, ATP content, calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II-III, and V) but was unable to modify renal and mitochondrial Cr(VI) content or to chelate chromium. Curcumin posttreatment was unable to prevent K(2)Cr(2)O(7)-induced renal dysfunction. In further experiments performed in curcumin (400 mg/kg)-pretreated rats it was found that this antioxidant accumulated in kidney and activated Nrf2 at the time when K(2)Cr(2)O(7) was injected, suggesting that both direct and indirect antioxidant effects are involved in the protective effects of curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of curcumin pretreatment against K(2)Cr(2)O(7)-induced renal oxidant damage.
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, 04510 University City, DF, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Jijón
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Hafidi
authors.forename: Zyanya Lucia
authors.initials: ZL
authors.lastname: Zatarain-Barrón
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.forename: Omar Noel
authors.initials: ON
authors.lastname: Medina-Campos
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zarco-Márquez
authors.forename: Ismael
authors.initials: I
authors.lastname: Torres
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D002274:Carcinogens, Environmental / Q000008:administration & dosage; D002857:Chromium / Q000008:administration & dosage; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D002274:Carcinogens, Environmental; D051267:NF-E2-Related Factor 2; D002857:Chromium; C074702:chromium hexavalent ion; D003474:Curcumin