title: Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: role of Cr(VI) chelation.
abstract: Deferoxamine (DFO) is a recognized iron chelator which has been shown to exert nephroprotection in models of toxic nephropathies. In the present work the potential protective effects of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress were evaluated. Rats were injected with a single injection (15mg/kg, s.c.) of potassium dichromate (K(2)Cr(2)O(7)). DFO was given as a single i.p. injection 30min before K(2)Cr(2)O(7) administration at three different doses (100, 200 and 400mg/kg). It was found that DFO pretreatment attenuated, in a dose-dependent way, K(2)Cr(2)O(7)-induced renal dysfunction and structural alterations evaluated by serum creatinine, blood urea nitrogen, creatinine clearance, proteinuria, plasma glutathione peroxidase activity, urinary excretion of N-acetyl-β-d-glucosaminidase and histological analyses. Furthermore, DFO prevented the K(2)Cr(2)O(7)-induced renal oxidant stress and the decrease in the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. Finally it was found that DFO, at 400mg/kg, decreases renal Cr(VI) content which prompted us to evaluate the potential Cr(VI) chelating properties of this compound. Indeed was found in an in vitro assay that DFO was an effective Cr(VI) chelator with an IC(50) of 800μg. In additional groups of rats was found that DFO posttreatment was ineffective to attenuate K(2)Cr(2)O(7)-induced nephrotoxicity and renal oxidant stress. Furthermore, DFO was unable to modify urinary excretion of total chromium. The nephroprotective effect of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content. However, it cannot be excluded that the ability of DFO to chelate iron may also be involved in the protection observed in our study.
authors: Faculty of Chemistry, Department of Biology, National Autonomous University of Mexico (UNAM), University City, 04510, D.F., Mexico.
authors: Eduardo
authors: E
authors: Molina-Jijón
authors: Guillermo
authors: G
authors: Zarco-Márquez
authors: Omar Noel
authors: ON
authors: Medina-Campos
authors: Zyanya Lucía
authors: ZL
authors: Zataraín-Barrón
authors: Rogelio
authors: R
authors: Hernández-Pando
authors: Enrique
authors: E
authors: Pinzón
authors: Rosa Marina
authors: RM
authors: Zavaleta
authors: Edilia
authors: E
authors: Tapia
authors: José
authors: J
authors: Pedraza-Chaverri
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D002857:Chromium / Q000037:antagonists & inhibitors* / Q000633:toxicity* / Q000652:urine; D003676:Deferoxamine / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011192:Potassium Dichromate / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000931:Antidotes; D002614:Chelating Agents; D007202:Indicators and Reagents; D002857:Chromium; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D003676:Deferoxamine; D011192:Potassium Dichromate