Mythili Yenjerla, Sudharsan Periyasamy Thandavan, Sudhahar Varatharajan, Varalakshmi Palaninathan
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Eur J Pharmacol. 2006 Aug 14;543(1-3):92-6. doi: 10.1016/j.ejphar.2006.06.007. Epub 2006 Jun 9.
Cyclophosphamide is a potent alkylating agent used in cancer chemotherapy and immunosuppression. The present study is aimed at evaluating the role of a potent antioxidant lipoic acid in cyclophosphamide induced hyperlipidemic cardiomyopathy. Adult male Wistar rats were divided into four treatment groups. Two groups received single intraperitoneal injection of cyclophosphamide (200 mg/kg body weight) to induce cardiotoxicity, one of these groups received lipoic acid treatment (25 mg/kg body weight, orally for 10 days). A vehicle treated control group and a lipoic acid drug control were also included. Cyclophosphamide administration resulted in abnormal elevation of serum lipids. Similarly in the cardiac tissue, the levels of free cholesterol, esterified cholesterol, triglycerides were increased significantly (P<0.05) while the levels of phospholipids and free fatty acids were reduced significantly unlike serum (P<0.05). Serum Low Density Lipoprotein (LDL) and Very Low Density Lipoprotein (VLDL) cholesterol increased significantly (P<0.05) while High Density Lipoprotein (HDL) cholesterol (P<0.05) decreased significantly when compared to controls. These changes corroborated with the abnormal distortion in the activities of lipid metabolizing enzymes in cyclophosphamide treated group. Supplementation of lipoic acid reverted these abnormalities in the lipid levels and activities of lipid metabolizing enzymes to near normalcy after cyclophosphamide administration.
环磷酰胺是一种用于癌症化疗和免疫抑制的强效烷化剂。本研究旨在评估强效抗氧化剂硫辛酸在环磷酰胺诱导的高脂血症性心肌病中的作用。成年雄性Wistar大鼠被分为四个治疗组。两组接受单次腹腔注射环磷酰胺(200毫克/千克体重)以诱导心脏毒性,其中一组接受硫辛酸治疗(25毫克/千克体重,口服10天)。还包括一个赋形剂处理的对照组和一个硫辛酸药物对照组。给予环磷酰胺导致血清脂质异常升高。同样在心脏组织中,游离胆固醇、酯化胆固醇、甘油三酯水平显著升高(P<0.05),而磷脂和游离脂肪酸水平与血清不同,显著降低(P<0.05)。与对照组相比,血清低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL)胆固醇显著升高(P<0.05),而高密度脂蛋白(HDL)胆固醇显著降低(P<0.05)。这些变化与环磷酰胺处理组脂质代谢酶活性的异常改变相一致。给予环磷酰胺后补充硫辛酸可使脂质水平和脂质代谢酶活性的这些异常恢复到接近正常水平。