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五环三萜、羽扇豆醇及其酯对环磷酰胺诱导的氧化应激的心脏保护作用。

Cardioprotective effect of pentacyclic triterpene, lupeol and its ester on cyclophosphamide-induced oxidative stress.

作者信息

Sudharsan P T, Mythili Y, Selvakumar E, Varalakshmi P

机构信息

Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.

出版信息

Hum Exp Toxicol. 2005 Jun;24(6):313-8. doi: 10.1191/0960327105ht530oa.

Abstract

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In the present study, lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate were investigated for their possible cardioprotective effects against CP-induced toxicity. Male albino rats of Wistar strain were injected with a single dose of CP (200 mg/kg body weight, ip). In CP-administered rats, activities of lactate dehydrogenase and creatine phosphokinase were elevated in serum with a concomitant decline in their activities in the cardiac tissue. Significant increases (P<0.001) in the levels of lipid peroxides and a decrease (P<0.001) in the levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-s-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the heart were also observed. The cardioprotective effects of lupeol (50 mg/kg body weight for 10 days orally) and its ester, lupeol linoleate (50 mg/kg body weight for 10 days orally) were evident from the significant reversal of the above alterations induced by CP. These observations highlight the antioxidant property of triterpenes and their cytoprotective action against CP-induced cardiotoxicity.

摘要

环磷酰胺(CP)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,对从阔叶猕猴桃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CP诱导的毒性的潜在心脏保护作用进行了研究。给雄性Wistar品系白化大鼠注射单剂量的CP(200 mg/kg体重,腹腔注射)。在给予CP的大鼠中,血清中乳酸脱氢酶和肌酸磷酸激酶的活性升高,同时心脏组织中它们的活性下降。还观察到心脏中脂质过氧化物水平显著升高(P<0.001),而酶促抗氧化剂(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶和谷胱甘肽-S-转移酶)和非酶促抗氧化剂(还原型谷胱甘肽、维生素C和维生素E)水平下降(P<0.001)。羽扇豆醇(50 mg/kg体重,口服10天)及其酯亚油酸羽扇豆醇酯(50 mg/kg体重,口服10天)的心脏保护作用从CP诱导的上述改变的显著逆转中明显可见。这些观察结果突出了三萜类化合物的抗氧化特性及其对CP诱导的心脏毒性的细胞保护作用。

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