Naziroglu Mustafa, Karaoğlu Aziz, Aksoy Asude Orhan
Department of Physiology, Veterinary Faculty, Firat University, TR-23119, Elaziğ, Turkey.
Toxicology. 2004 Feb 15;195(2-3):221-30. doi: 10.1016/j.tox.2003.10.012.
Cisplatin is one of the most active cytotoxic agents in the treatment of cancer but its clinical use is associated with nephrotoxicity. Several studies suggest that supplementation with antioxidant can influence cisplatin induced nephrotoxicity. In the present study, we investigated the effect of selenium with high dose vitamin E administration on lipid peroxidation (MDA) and scavenging enzyme activity in kidneys, liver and lens of cisplatin-induced toxicity in rats. Forty female Wistar rats were used. They were randomly divided into five groups. The first and second groups were used as control and cisplatin (6 mg/kg BW) intraperitoneally administrated groups. Groups III, IV and V received intraperitoneally five doses of selenium (1.5 mg/kg BW) and a high dose of vitamin E (1000 mg/kg BW) combination before, simultaneously and after with cisplatin, respectively. Glutathione peroxidase (GSH-Px), vitamin E and beta-carotene levels in the kidney, lens and liver, vitamin A and reduced glutathione (GSH) levels in the kidney were significantly (P<0.05 to <0.001) lower in the cisplatin group than in the control whereas there was a significant increase in kidney, liver and lens MDA levels in rats treated with cisplatin. The decreased antioxidant enzymes and vitamins and increased MDA levels in the kidney, lens and liver of animals administered with cisplatin were significantly (P<0.05 to <0.001) improved with selenium and a high dose vitamin E injection. In conclusion, this data demonstrates that there is an increase in lipid peroxidation in the kidney, liver and lens of animals administered with cisplatin whereas there is a decrease in antioxidant vitamins and enzymes. However, intraperitoneally injected selenium combined with a high dose of vitamin E seem to produce a significant improvement on antioxidants concentrations in rats treated before, simultaneously and after with cisplatin. The selenium with high dose vitamin E injection may play a role in preventing cisplatin-induced nephropathy and cataract formation in cancer patient.
顺铂是治疗癌症最有效的细胞毒性药物之一，但其临床应用与肾毒性相关。多项研究表明，补充抗氧化剂可影响顺铂诱导的肾毒性。在本研究中，我们调查了高剂量维生素E联合硒给药对顺铂诱导的大鼠肾、肝和晶状体毒性中脂质过氧化（丙二醛）和清除酶活性的影响。使用了40只雌性Wistar大鼠。它们被随机分为五组。第一组和第二组用作对照组和顺铂（6mg/kg体重）腹腔注射组。第三组、第四组和第五组分别在顺铂给药前、同时和之后腹腔注射五剂硒（1.5mg/kg体重）和高剂量维生素E（1000mg/kg体重）的组合。顺铂组肾脏、晶状体和肝脏中的谷胱甘肽过氧化物酶（GSH-Px）、维生素E和β-胡萝卜素水平，以及肾脏中的维生素A和还原型谷胱甘肽（GSH）水平显著低于对照组（P<0.05至<0.001），而顺铂处理的大鼠肾脏、肝脏和晶状体中的丙二醛水平显著升高。顺铂给药动物的肾脏、晶状体和肝脏中抗氧化酶和维生素的降低以及丙二醛水平的升高，通过硒和高剂量维生素E注射得到了显著改善（P<0.05至<0.001）。总之，这些数据表明，顺铂给药动物的肾脏、肝脏和晶状体中脂质过氧化增加，而抗氧化维生素和酶减少。然而，腹腔注射硒联合高剂量维生素E似乎对顺铂给药前、同时和之后处理的大鼠的抗氧化剂浓度有显著改善作用。高剂量维生素E注射的硒可能在预防癌症患者顺铂诱导的肾病和白内障形成中发挥作用。
