Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, 04510 University City, DF, Mexico.
Free Radic Biol Med. 2011 Oct 15;51(8):1543-57. doi: 10.1016/j.freeradbiomed.2011.07.018. Epub 2011 Jul 29.
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.
我们报告了线粒体在姜黄素（一种众所周知的直接和间接抗氧化剂）对六价铬[Cr(VI)]化合物重铬酸钾（K(2)Cr(2)O(7)）诱导的大鼠肾氧化剂损伤的保护作用中的作用。姜黄素通过灌胃每天给予三种不同的方案：（1）完全治疗（100、200 和 400 mg/kg bw 在 K(2)Cr(2)O(7) 注射前 10 天和 2 天），（2）预处理（400 mg/kg bw 在 K(2)Cr(2)O(7) 注射前 10 天），和（3）后处理（K(2)Cr(2)O(7) 注射后 2 天给予 400 mg/kg bw）。单次 K(2)Cr(2)O(7)（15 mg/kg，sc）注射后 48 小时处死大鼠，以评估肾和线粒体功能以及氧化应激。姜黄素治疗（方案 1 和 2）减轻了 K(2)Cr(2)O(7) 诱导的肾功能障碍、组织损伤、氧化应激和抗氧化酶活性的降低，无论是在肾组织还是线粒体中。姜黄素预处理减轻了 K(2)Cr(2)O(7) 诱导的线粒体功能障碍（氧消耗、ATP 含量、钙保留和线粒体膜电位的改变以及复合物 I、II、II-III 和 V 的活性降低），但无法改变肾和线粒体中的 Cr(VI)含量或螯合铬。姜黄素后处理不能预防 K(2)Cr(2)O(7) 诱导的肾功能障碍。在对姜黄素（400 mg/kg）预处理大鼠进行的进一步实验中发现，这种抗氧化剂在注射 K(2)Cr(2)O(7) 时积聚在肾脏中并激活了 Nrf2，这表明直接和间接抗氧化作用都参与了姜黄素的保护作用。这些发现表明，线粒体功能的保存在姜黄素预处理对 K(2)Cr(2)O(7) 诱导的肾氧化剂损伤的保护作用中起着关键作用。
