Faculty of Chemistry, Department of Biology, National Autonomous University of Mexico (UNAM), University City, 04510, D.F., Mexico.
Toxicology. 2012 Jan 27;291(1-3):93-101. doi: 10.1016/j.tox.2011.11.003. Epub 2011 Nov 15.
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.
去铁胺（DFO）是一种公认的铁螯合剂，已被证明在毒性肾病模型中具有肾保护作用。在本工作中，评估了 DFO 对 Cr(VI)诱导的肾毒性和氧化应激的潜在保护作用。大鼠单次皮下注射（15mg/kg）重铬酸钾（K(2)Cr(2)O(7)）。DFO 于 K(2)Cr(2)O(7)给药前 30 分钟单次腹腔注射，剂量分别为 100、200 和 400mg/kg。结果发现，DFO 预处理以剂量依赖性方式减弱了 K(2)Cr(2)O(7)诱导的肾功能障碍和结构改变，血清肌酐、血尿素氮、肌酐清除率、蛋白尿、血浆谷胱甘肽过氧化物酶活性、尿 N-乙酰-β-d-葡萄糖苷酶排泄和组织学分析。此外，DFO 还可预防 K(2)Cr(2)O(7)诱导的肾氧化应激和抗氧化酶超氧化物歧化酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶和过氧化氢酶活性的降低。最后发现，DFO（400mg/kg）可降低肾 Cr(VI)含量，促使我们评估该化合物对 Cr(VI)的潜在螯合作用。事实上，在体外试验中发现 DFO 是一种有效的 Cr(VI)螯合剂，IC(50)为 800μg。在大鼠的其他组中发现，DFO 后处理对减轻 K(2)Cr(2)O(7)诱导的肾毒性和肾氧化应激无效。此外，DFO 无法改变总铬的尿排泄。DFO 对 Cr(VI)诱导的肾毒性和氧化应激的肾保护作用可能至少部分归因于 DFO 螯合 Cr(VI)和降低肾 Cr(VI)含量的能力。然而，不能排除 DFO 螯合铁的能力也可能参与了我们研究中观察到的保护作用。
