Sudharsan P T, Mythili Y, Sudhahar V, Varalakshmi P
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
J Pharm Pharmacol. 2005 Nov;57(11):1437-44. doi: 10.1211/jpp.57.11.0009.
Cyclophosphamide, an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In this study, lupeol, a pentacyclic triterpene isolated from Crataeva nurvala stem bark, and its ester, lupeol linoleate, were investigated for their possible hypocholesterolaemic effects against cyclophosphamide-induced lipidaemic instabilities. Male albino Wistar rats were categorized into 6 groups. Group I served as control. Rats in groups II, V and VI were injected intraperitoneally with a single dose of cyclophosphamide (200 mg kg(-1)) dissolved in saline. Cyclophosphamide-treated groups V and VI respectively received lupeol and lupeol linoleate (50 mg kg(-1)), dissolved in olive oil, for 10 days by oral gavage. Groups III and IV served as drug controls and were administered lupeol and lupeol linoleate, respectively. Cyclophosphamide administration induced abnormal changes in serum lipoproteins and lipid fractions in both serum and cardiac tissue. The activity of lipid metabolizing enzymes was distorted significantly in the cyclophosphamide-treated rats. The cyclophosphamide-treated rats also showed extensive intermuscular haemorrhage in histology. Lupeol and its ester reversed the above alterations induced by cyclophosphamide. This study encapsulates the early lipaemic abnormalities in the heart tissue of cyclophosphamide-treated rats. Treatment with lupeol linoleate was more effective than lupeol in rendering protection to the cardiac tissue challenged by cyclophosphamide.
环磷酰胺是一种广泛用于癌症化疗的烷化剂，会导致致命的心脏毒性。在本研究中，对从瓦氏辣木茎皮中分离出的五环三萜羽扇豆醇及其酯亚油酸羽扇豆醇酯针对环磷酰胺诱导的血脂异常的可能降胆固醇作用进行了研究。将雄性白化Wistar大鼠分为6组。第一组作为对照。第二、五和六组的大鼠腹腔注射一剂溶解于生理盐水的环磷酰胺（200 mg kg⁻¹）。环磷酰胺处理组的第五和六组分别通过口服灌胃给予溶解于橄榄油的羽扇豆醇和亚油酸羽扇豆醇酯（50 mg kg⁻¹），持续10天。第三和四组作为药物对照组，分别给予羽扇豆醇和亚油酸羽扇豆醇酯。给予环磷酰胺导致血清脂蛋白以及血清和心脏组织中的脂质成分出现异常变化。环磷酰胺处理的大鼠中脂质代谢酶的活性显著失调。环磷酰胺处理的大鼠在组织学上还表现出广泛的肌间出血。羽扇豆醇及其酯逆转了环磷酰胺诱导的上述改变。本研究概括了环磷酰胺处理的大鼠心脏组织中的早期血脂异常。亚油酸羽扇豆醇酯处理在保护受环磷酰胺攻击的心脏组织方面比羽扇豆醇更有效。
