Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110 062, India.
Br J Nutr. 2013 Aug;110(4):699-710. doi: 10.1017/S0007114512005752. Epub 2013 Feb 12.
Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties. In this study, we used DM as a protective agent against the nephrotoxic effects of the environmental toxicant trichloroethylene (TCE). Male Wistar rats were divided into five groups (I-V, n 6). Groups II, III and IV received an oral administration of TCE at a dose of 1000 mg/kg body weight for twenty consecutive days. The animals in groups II and III received an oral treatment of DM at doses of 20 and 40 mg/kg body weight, respectively, for twenty consecutive days, while groups I and V were given maize oil (5 ml/kg body weight and DM 40 mg/kg body weight, respectively) for 20 d. The protective effects of DM on TCE-induced oxidative stress and caspase-dependent apoptosis were investigated by assaying oxidative stress biomarkers, lipid peroxidation (LPO), serum toxicity markers, alkaline unwinding assay, caspase-3, -7 and -9, Bax and p53 expression. Oral administration of TCE in rats enhanced renal LPO, depleted glutathione content and antioxidant enzymes, induced DNA strand breaks (P<0·001), modulated the expression of Bax and p53 protein and induced the expression of caspase-3, -7 and -9. Co-treatment with DM prevented oxidative stress by restoring the levels of antioxidant enzymes; furthermore, a significant dose-dependent decrease in DNA disintegration and kidney toxicity markers such as blood urea N, creatinine, lactate dehydrogenase and kidney injury molecule-1 was observed. DM also effectively decreased the TCE-induced up-regulation of Bax and p53. Data from the present study establish the protective role of DM against TCE-induced renal damage.
地奥司明（DM）是一种天然存在的黄酮类化合物，已被发现具有多种治疗特性。在这项研究中，我们使用 DM 作为一种保护剂，防止环境毒物三氯乙烯（TCE）的肾毒性作用。雄性 Wistar 大鼠被分为五组（I-V，n 6）。第 II、III 和 IV 组连续 20 天口服 TCE 剂量为 1000mg/kg 体重。第 II 组和第 III 组的动物分别口服 DM 剂量为 20 和 40mg/kg 体重，连续 20 天，而第 I 组和第 V 组分别给予玉米油（5ml/kg 体重和 DM 40mg/kg 体重）20 天。通过测定氧化应激生物标志物、脂质过氧化（LPO）、血清毒性标志物、碱性解旋试验、caspase-3、-7 和 -9、Bax 和 p53 表达，研究 DM 对 TCE 诱导的氧化应激和 caspase 依赖性细胞凋亡的保护作用。TCE 灌胃大鼠增强肾脏 LPO，耗竭谷胱甘肽含量和抗氧化酶，诱导 DNA 链断裂（P<0·001），调节 Bax 和 p53 蛋白表达，并诱导 caspase-3、-7 和 -9 表达。DM 与 TCE 共同处理通过恢复抗氧化酶水平来防止氧化应激；此外，还观察到 DNA 崩解和肾毒性标志物如血尿素氮、肌酐、乳酸脱氢酶和肾损伤分子-1 的显著剂量依赖性降低。DM 还能有效降低 TCE 诱导的 Bax 和 p53 上调。本研究数据确立了 DM 对 TCE 诱导的肾损伤的保护作用。
