Original Contribution Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway Eduardo Molina-Jijón a , Edilia Tapia b , Cecilia Zazueta c , Mohammed El Hafidi d , Zyanya Lucia Zatarain-Barrón e , Rogelio Hernández-Pando e , Omar Noel Medina-Campos a , Guillermo Zarco-Márquez a , Ismael Torres f , José Pedraza-Chaverri a, ⁎ a Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, 04510 University City, D.F., Mexico b Department of Nephrology, National Institute of Cardiology “Ignacio Chávez,” 14080 Mexico, D.F., Mexico c Department of Biochemistry, National Institute of Cardiology “Ignacio Chávez,” 14080 Mexico, D.F., Mexico d Department of Cardiovascular Biomedicine, National Institute of Cardiology “Ignacio Chávez,” 14080 Mexico, D.F., Mexico e Experimental Pathology Section, National Institute of Medical Sciences and Nutrition “Salvador Zubirán,” 14000 Mexico, D.F., Mexico f Animal Care Unit, Faculty of Medicine, National Autonomous University of Mexico, 04510 University City, D.F., Mexico abstract article info Article history: Received 27 February 2011 Revised 11 July 2011 Accepted 21 July 2011 Available online 29 July 2011 Keywords: Curcumin Chromium Nephrotoxicity Mitochondrial dysfunction Oxidant stress Free radicals 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. © 2011 Elsevier Inc. All rights reserved. Curcumin (diferuloylmethane) is a naturally occurring phenolic compound isolated as a yellow pigment from turmeric (Curcuma longa), which is commonly used as a spice, additive, and food colorant [1]. Curcumin is well documented for its medicinal properties in traditional Indian medicine [2]. The compound has been reported to possess antioxidant [3,4], anti-inflammatory [5,6], antimicrobial [7], and anticancer properties [8] and thus has a potential protective effect against various malignant diseases [1]. Curcumin has been shown to be a potent scavenger of a variety of reactive oxygen species (ROS), including superoxide anion, hydroxyl radical [9], and nitrogen dioxide radical [10,11]. Phase II enzymes, including glutathione S-transferase (GST), heme oxygenase 1 (HO-1), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and nicotinamide adenine dinucleotide phosphate reduced form (NADPH) quinone oxidoreductase 1 (NQO1), protect cells from oxidant stress by detoxifying carcinogens or reducing oxidant stress [12], and curcumin has been shown to increase the expression of these enzymes by inducing nuclear translocation of the nuclear factor-E2-related factor 2 (Nrf2). The Free Radical Biology & Medicine 51 (2011) 1543–1557 Abbreviations: BHT, butylated hydroxytoluene; BUN, blood urea nitrogen; CAT, catalase; CCCP, m-chlorophenylhydrazone; CDNB, 1-chloro-2,4-dinitrobenzene; CUR, curcumin; DNPH, 2,4-dinitrophenylhydrazine; DPPH, 2,2-diphenyl-1-picrylhydrazyl radical; EDTA, ethylenediaminetetraacetic acid; G6PDH, glucose-6-phosphate dehy- drogenase; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, glutathione reduced form; GSSG, glutathione oxidized form; GST, glutathione S-transferase; Hepes, N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid); HPLC, high-pressure liquid chromatography; 4-HNE, 4-hydroxy-2-nonenal; HO-1, heme oxygenase 1; MDA, malondialdehyde; NAC, N-acetylcysteine; NAG, N-acetyl-β-D-glucosaminidase; NBT, nitroblue tetrazolium; NQO1, NADPH quinone oxidoreductase 1; Nrf2, nuclear factor- E2-related factor 2; P i , inorganic phosphate; PMS, phenazine methosulfate; RC, respiratory control index; ROS, reactive oxygen species; SOD, superoxide dismutase; TCA, trichloroacetic acid; TMPD, N′,N′,N′,N-tetramethyl-p-phenylendiamide. ⁎ Corresponding author. Fax: + 52 55 5622 3878. E-mail address: pedraza@unam.mx (J. Pedraza-Chaverri). 0891-5849/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.freeradbiomed.2011.07.018 Contents lists available at ScienceDirect Free Radical Biology & Medicine journal homepage: www.elsevier.com/locate/freeradbiomed