Kuhad Anurag, Pilkhwal Sangeeta, Sharma Sameer, Tirkey Naveen, Chopra Kanwaljit
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, Chandigarh-160014, India.
J Agric Food Chem. 2007 Dec 12;55(25):10150-5. doi: 10.1021/jf0723965. Epub 2007 Nov 15.
Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin-induced acute renal failure. Curcumin is claimed to be a potent anti-inflammatory and antioxidant agent. The present study was performed to explore the effect of curcumin against cisplatin-induced experimental nephrotoxicity. Curcumin in the dosages of 15, 30, and 60 mg kg(-1) was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance, and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. Systemic inflammation was assessed by tumor necrosis factor-alpha (TNF-alpha) levels. A single dose of cisplatin resulted in marked inflammation (486% rise in TNF-alpha level) and oxidative stress and significantly deranged renal functions as well as renal morphology. The serum TNF-alpha level was markedly reduced in curcumin-treated rats. Curcumin treatment significantly and dose-dependently restored renal function, reduced lipid peroxidation, and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. The present study demonstrates that curcumin has a protective effect on cisplatin-induced experimental nephrotoxicity, and this effect is attributed to its direct anti-inflammatory and strong antioxidant profile. Hence, curcumin has a strong potential to be used as a therapeutic adjuvant in cisplatin nephrotoxicity.
肾毒性是顺铂治疗的主要并发症和剂量限制因素。最近的证据表明，炎症和氧化应激可能在顺铂诱导的急性肾衰竭发病机制中起作用。姜黄素据称是一种有效的抗炎和抗氧化剂。本研究旨在探讨姜黄素对顺铂诱导的实验性肾毒性的影响。在顺铂给药前2天和给药后3天给予剂量为15、30和60 mg/kg(-1)的姜黄素。通过测量血清肌酐、血尿素氮、肌酐、尿素清除率和血清亚硝酸盐水平来评估肾损伤。通过测定肾丙二醛水平、还原型谷胱甘肽水平以及超氧化物歧化酶和过氧化氢酶的酶活性来评估肾氧化应激。通过肿瘤坏死因子-α（TNF-α）水平评估全身炎症。单次给予顺铂导致明显的炎症（TNF-α水平升高486%）和氧化应激，并显著扰乱肾功能以及肾脏形态。在姜黄素治疗的大鼠中，血清TNF-α水平明显降低。姜黄素治疗显著且剂量依赖性地恢复肾功能，减少脂质过氧化，并提高还原型谷胱甘肽水平以及超氧化物歧化酶和过氧化氢酶的活性。本研究表明，姜黄素对顺铂诱导的实验性肾毒性具有保护作用，这种作用归因于其直接的抗炎和强大的抗氧化特性。因此，姜黄素具有很强的潜力可作为顺铂肾毒性的治疗辅助药物。
