Post-Graduate Department of Biochemistry, Bharathi Women's College (Autonomous), Prakasam Salai, North Chennai 600 108, Tamil Nadu, India.
Pharmacol Rep. 2013;65(5):1336-44. doi: 10.1016/s1734-1140(13)71492-0.
Clinically, chronic nephrotoxicity may lead to renal functional impairment and progress to end stage renal failure. The renoprotective effect of a flavonoid naringin (NG) against cyclosporine A (CsA)-induced nephrotoxicitywas investigated in this study.
Nephrotoxicity was induced in male albino Wistar rats by injecting 25 mg/kg body weight of CsAfor a period of 21 days. CsA-induced rats were also cotreated with 40 mg of NG/kg body weight, orally.
After the experimental period, the levels of lipid peroxides (TBARS) and hydroxyl radical (OH·) were found to be elevated, whereas the levels of SOD, catalase, glutathione, vitamin C, E and A were decreased in CsA-induced rats. NG co-treatment significantly decreased the levels of lipid peroxides and hydroxyl radicals and restored the levels of enzymic and non-enzymic antioxidants in renal tissues. Histological analysis revealed that CsA administration caused severe and widespread necrosis with dilatation of proximal tubules, vacuolization, tubular cell desquamation and intraluminal cast formation with massive infiltration of inflammatory cells. CsA-induced histopathological renal changes were minimal in animals which received NG treatment. The western blot and confocal microscopic expression of heme oxygenase-1 was restored by NG. In CsA-induced animals the expression was reduced compared to NG treated animals.
The present study reveals that NG can act as effective renoprotective drug against CsA-induced toxicity.
临床上，慢性肾毒性可导致肾功能损害，并进展为终末期肾衰竭。本研究旨在探讨类黄酮柚皮苷（NG）对环孢素 A（CsA）诱导的肾毒性的肾保护作用。
通过给雄性白化 Wistar 大鼠注射 25mg/kg 体重的 CsA 21 天，诱导产生肾毒性。同时，CsA 诱导的大鼠给予 40mg/kg 体重的 NG 进行口服治疗。
在实验期结束后，发现 CsA 诱导的大鼠的脂质过氧化物（TBARS）和羟基自由基（OH·）水平升高，而肾组织中的 SOD、过氧化氢酶、谷胱甘肽、维生素 C、E 和 A 的水平降低。NG 联合治疗可显著降低脂质过氧化物和羟基自由基的水平，并恢复肾组织中酶和非酶抗氧化剂的水平。组织学分析显示，CsA 给药导致严重且广泛的坏死，伴有近端小管扩张、空泡化、肾小管细胞脱落和管腔内铸型形成，并伴有大量炎症细胞浸润。接受 NG 治疗的动物肾组织的 CsA 诱导的组织病理学变化最小。NG 还可恢复血红素加氧酶-1 的 Western blot 和共聚焦显微镜表达。与 NG 处理的动物相比，CsA 诱导的动物中的表达减少。
本研究表明，NG 可作为一种有效的 CsA 诱导毒性的肾保护药物。
