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DL-α-硫辛酸对环磷酰胺诱导的氧化心脏毒性中溶酶体变化的影响。

Effect of DL-alpha-lipoic acid on cyclophosphamide induced lysosomal changes in oxidative cardiotoxicity.

作者信息

Mythili Y, Sudharsan P T, Amudha G, 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 - 600 113, India.

出版信息

Life Sci. 2007 May 1;80(21):1993-8. doi: 10.1016/j.lfs.2007.02.040. Epub 2007 Mar 12.

Abstract

Cyclophosphamide (CP), one of the widely prescribed antineoplastic drugs can cause fatal cardiotoxicity. The present study is aimed at evaluating the cardioprotective role of lipoic acid in CP induced toxicity. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I served as control, Group II received a single dose of CP (200 mg/kg b.wt., i.p.), Group III received lipoic acid (25 mg/kg b.wt., orally) for 10 days, and Group IV received CP immediately followed by lipoic acid for 10 days. In CP administered rats, the levels of protein carbonyl and 8-hydroxy-2-deoxyguanosine were increased significantly (P<0.001) indicating oxidative changes in the heart tissue. The activities of lysosomal acid hydrolases, beta-Glu, beta-Gal, NAG, Cat-D and ACP increased significantly (P<0.001) in the serum as well as in the heart tissue after CP administration. An increase in hydroxyproline was observed in CP induced rats. Lipoic acid effectively reverted these abnormal biochemical changes to near normalcy. These observations highlight the protective role of lipoic acid in CP induced cardiotoxicity.

摘要

环磷酰胺(CP)是一种广泛使用的抗肿瘤药物,可导致致命的心脏毒性。本研究旨在评估硫辛酸在CP诱导的毒性中的心脏保护作用。将雄性Wistar品系白化大鼠分为四组,并进行如下处理:第一组作为对照组,第二组接受单次剂量的CP(200 mg/kg体重,腹腔注射),第三组口服硫辛酸(25 mg/kg体重),持续10天,第四组在接受CP后立即给予硫辛酸,持续10天。在给予CP的大鼠中,蛋白质羰基和8-羟基-2-脱氧鸟苷水平显著升高(P<0.001),表明心脏组织发生氧化变化。给予CP后,血清和心脏组织中溶酶体酸性水解酶、β-葡萄糖苷酶、β-半乳糖苷酶、N-乙酰-β-D-氨基葡萄糖苷酶、组织蛋白酶D和酸性磷酸酶的活性显著增加(P<0.001)。在CP诱导的大鼠中观察到羟脯氨酸增加。硫辛酸有效地将这些异常生化变化恢复到接近正常水平。这些观察结果突出了硫辛酸在CP诱导的心脏毒性中的保护作用。

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