Adhirai M, Selvam R
Department of Biochemistry, Dr A. L. M. PG Institute of Basic Medical Sciences, University of Madras, Taramani, India.
J Pharm Pharmacol. 1998 May;50(5):501-5. doi: 10.1111/j.2042-7158.1998.tb06191.x.
This study aimed to evaluate whether administration of cyclosporin to hyperoxaluric rats affects liver antioxidant status, and whether pretreatment with vitamin E reverses the effect. Male Wistar rats were divided into two major groups of 40. One group was given vitamin E. Both major groups were then divided into four subgroups which received vehicle (olive oil), cyclosporin in olive oil (50 mg kg(-1)), 3% ammonium oxalate or cyclosporin + 3% ammonium oxalate for three days. The activities of liver lactate dehydrogenase, glycolic acid oxidase and xanthine oxidase, and the level of malondialdehyde, an indicator of lipid peroxidation, increased when cyclosporin was administered to hyperoxaluric rats. The levels of antioxidants ascorbic acid, vitamin E and reduced glutathione and the activities of glutathione-metabolizing enzymes were altered significantly when hyperoxaluric rats were treated with cyclosporin. All these enzymes and antioxidants showed highly significant correlation values, r. These changes were restored to near normal by pretreatment with vitamin E. These findings suggest that cyclosporin-induced hepatotoxicity is aggravated in hyperoxaluria. This was almost totally prevented by pretreatment with vitamin E.
本研究旨在评估给高草酸尿症大鼠施用环孢素是否会影响肝脏抗氧化状态，以及维生素E预处理是否能逆转这种影响。雄性Wistar大鼠被分为两个主要组，每组40只。一组给予维生素E。然后将两个主要组均分为四个亚组，分别接受赋形剂（橄榄油）、橄榄油中的环孢素（50 mg kg⁻¹）、3%草酸铵或环孢素 + 3%草酸铵，持续三天。当给高草酸尿症大鼠施用环孢素时，肝脏乳酸脱氢酶、乙醇酸氧化酶和黄嘌呤氧化酶的活性以及脂质过氧化指标丙二醛的水平均升高。当高草酸尿症大鼠用环孢素治疗时，抗氧化剂抗坏血酸、维生素E和还原型谷胱甘肽的水平以及谷胱甘肽代谢酶的活性均发生显著改变。所有这些酶和抗氧化剂均显示出高度显著的相关值r。通过维生素E预处理，这些变化恢复到接近正常水平。这些发现表明，高草酸尿症会加重环孢素诱导的肝毒性。而维生素E预处理几乎完全预防了这种情况。
