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脂抑素对白化病大鼠阿霉素诱导的心肌毒性的心脏保护作用。

Cardioprotective effect of lipistat against doxorubicin induced myocardial toxicity in albino rats.

作者信息

Koti B C, Vishwanathswamy A H M, Wagawade Jyoti, Thippeswamy A H M

机构信息

Department of Pharmacology, K L E Society's College of Pharmacy, Hubli 580 031, India.

出版信息

Indian J Exp Biol. 2009 Jan;47(1):41-6.

Abstract

Preventive role of lipistat against doxorubicin induced myocardial toxicity in rats has been reported. Cardiotoxicity was produced by doxorubicin administration (15 mg/kg for 2 weeks). Lipistat (350 mg/kg, orally) was administered as pretreatment for 2 weeks and then for 2 weeks alternated with doxorubicin. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), serum lipid profiles like total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were monitored after 3 weeks of last dose. Pretreatment with the lipistat significantly protected myocardium from the toxic effects of doxorubicin by reducing the elevated level of biomarker enzymes like LDH and CPK to the normal and serum lipids such as total cholesterol, triglyceride and LDL back to normal. Lipistat increases the decreased level of GSH, SOD and CAT and decreases the increased level of malondialdehyde in cardiac tissue. The repeated administration of doxorubicin causes cardiomyopathy associated with an antioxidant deficit and increased level of lipid profiles by interfering with fatty acid metabolism. The results support the lipid lowering and antioxidant properties of lipistat, which indicate the cardioprotective property against doxorubicin induced cardiotoxicity.

摘要

已有报道称脂脂妥对阿霉素诱导的大鼠心肌毒性具有预防作用。通过给予阿霉素(15mg/kg,持续2周)产生心脏毒性。脂脂妥(350mg/kg,口服)作为预处理给药2周,然后与阿霉素交替给药2周。在最后一次给药3周后监测一般观察指标、死亡率、组织病理学、生物标志物酶如乳酸脱氢酶(LDH)和肌酸磷酸激酶(CPK)、血脂谱如总胆固醇、甘油三酯、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)、抗氧化酶如谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)。脂脂妥预处理通过将升高的生物标志物酶如LDH和CPK水平降至正常,以及将血脂如总胆固醇、甘油三酯和LDL恢复正常,显著保护心肌免受阿霉素的毒性作用。脂脂妥可提高心脏组织中降低的GSH、SOD和CAT水平,并降低升高的丙二醛水平。反复给予阿霉素会导致与抗氧化剂缺乏相关的心肌病,并通过干扰脂肪酸代谢使血脂水平升高。这些结果支持了脂脂妥的降脂和抗氧化特性,表明其对阿霉素诱导的心脏毒性具有心脏保护作用。

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