Malarkodi Kumaravel Palanichamy, Balachandar Andithangal Venkatesan, Sivaprasad Rajagopalan, Varalakshmi Palaninathan
Department of Medical Biochemistry, Dr. A.L.M., Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.
Ren Fail. 2003 May;25(3):367-77. doi: 10.1081/jdi-120021151.
Adriamycin (ADR), which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in many organs. The present study was designed to investigate the effect of lipoic acid (LA) against acute ADR induced peroxidative damages in rat kidney. The study was carried out with adult male albino rats of Wistar strain, which comprised of one control and three experimental groups. Group I rats served as controls. Group II rats received ADR (7.5mg/kg body weight) intravenously through the tail vein. Group III rats were given LA (75 mg/kg body weight) intraperitoneally. Group IV rats were given LA one day before the administration of ADR. Rats subjected to ADR administration showed a decline in the thiol capacity of the cell accompanied by high malondialdehyde (MDA) levels along with lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) glutathione (GSH) and GSH metabolizing enzymes (glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD)). However no significant change was observed in the activity of glutathione-S-transferees (GST). Pretreatment with LA showed considerable changes over oxidative stress parameters. Nephrotoxic damage was evident from the decrease in the activities of gamma-glutamyl transferase (gamma-GT) and beta-glucuronidase (beta-GLU), which were reverted upon LA pretreatment.
This study has highlighted the beneficial effects of LA pretreatment in reversing the damages caused by ADR, by bringing about an improvement in the reductive status of the cell.
阿霉素(ADR)广泛用于治疗各种肿瘤疾病,但会对许多器官产生毒性作用。本研究旨在探讨硫辛酸(LA)对阿霉素诱导的大鼠肾脏急性过氧化损伤的影响。研究采用成年雄性Wistar品系白化大鼠,分为一个对照组和三个实验组。第一组大鼠作为对照。第二组大鼠通过尾静脉静脉注射阿霉素(7.5mg/kg体重)。第三组大鼠腹腔注射硫辛酸(75mg/kg体重)。第四组大鼠在注射阿霉素前一天给予硫辛酸。接受阿霉素注射的大鼠细胞巯基含量下降,丙二醛(MDA)水平升高,同时过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽(GSH)和GSH代谢酶(谷胱甘肽还原酶(GR)、葡萄糖-6-磷酸脱氢酶(G6PD))活性降低。然而,谷胱甘肽-S-转移酶(GST)的活性没有明显变化。硫辛酸预处理后,氧化应激参数有显著变化。γ-谷氨酰转移酶(γ-GT)和β-葡萄糖醛酸酶(β-GLU)活性降低表明肾毒性损伤明显,而硫辛酸预处理可使其恢复。
本研究强调了硫辛酸预处理通过改善细胞还原状态对逆转阿霉素所致损伤的有益作用。