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水飞蓟素可预防阿霉素诱导的大鼠心脏毒性和肾毒性。

Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats.

作者信息

El-Shitany Nagla A, El-Haggar Sahar, El-desoky Karema

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, Tanta University, Tanta, Egypt.

出版信息

Food Chem Toxicol. 2008 Jul;46(7):2422-8. doi: 10.1016/j.fct.2008.03.033. Epub 2008 Apr 7.

Abstract

Adriamycin is a potent anticancer agent, its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study aimed to investigate the possible protective role of the natural antioxidant silymarin on ADR-induced heart and kidney toxicity. Studies were performed on four groups of rats. 1--control group, 2--silymarin group (50 mg/kg), 3--adriamycin group (10 mg/kg), 4--adriamycin+silymarin group. On the third day after ADR injection, plasma was separated for determination of LDH, CPK, cholesterol and total lipids. 30 days after ADR injection, plasma was separated for determination of creatinine and urea levels. Frozen heart specimens (72 h) and frozen kidney specimens (30days) were used for estimation of lipid peroxides and GSH contents. Histopathological examinations of heart and kidney sections were also done. Pretreatment of ADR-treated rats with silymarin resulted in a significant decrease in the plasma CPK, LDH, creatinine and urea. On the other hand silymarin pretreatment did not change ADR-induced hyperlipidemia. Silymarin pretreatment significantly decreased the myocardial MDA contents. In addition, silymarin pretreatment normalized renal tissue contents of MDA and GSH. Histopathological examination of heart and kidney sections revealed that ADR caused only mild myocardial injury in silymarin pretreated rats. Also, silymarin pretreatment inhibited ADR-induced renal tubular damage in rats. These results have suggested that, silymarin ameliorated ADR-induced cardiotoxicity and protected against ADR-induced nephrotoxicity in male albino rats. The mechanisms of silymarin induced protection against ADR-induced toxicities were proved to be due to inhibition of lipid peroxidation and protection against GSH depletion.

摘要

阿霉素是一种强效抗癌药物,但其临床应用因显著的心脏毒性和肾毒性而受到限制。本研究旨在探讨天然抗氧化剂水飞蓟素对阿霉素诱导的心脏和肾脏毒性可能具有的保护作用。对四组大鼠进行了研究。1组为对照组,2组为水飞蓟素组(50毫克/千克),3组为阿霉素组(10毫克/千克),4组为阿霉素+水飞蓟素组。在注射阿霉素后的第三天,分离血浆以测定乳酸脱氢酶(LDH)、肌酸磷酸激酶(CPK)、胆固醇和总脂质。在注射阿霉素30天后,分离血浆以测定肌酐和尿素水平。使用冷冻心脏标本(72小时)和冷冻肾脏标本(30天)来评估脂质过氧化物和谷胱甘肽(GSH)含量。还对心脏和肾脏切片进行了组织病理学检查。用水飞蓟素预处理阿霉素处理的大鼠后,血浆中的CPK、LDH、肌酐和尿素显著降低。另一方面,水飞蓟素预处理并未改变阿霉素诱导的高脂血症。水飞蓟素预处理显著降低了心肌丙二醛(MDA)含量。此外,水飞蓟素预处理使肾脏组织中MDA和GSH的含量恢复正常。心脏和肾脏切片的组织病理学检查显示,在用水飞蓟素预处理的大鼠中,阿霉素仅引起轻度心肌损伤。而且,水飞蓟素预处理抑制了阿霉素诱导的大鼠肾小管损伤。这些结果表明,水飞蓟素改善了阿霉素诱导的心脏毒性,并对雄性白化大鼠阿霉素诱导的肾毒性具有保护作用。事实证明,水飞蓟素诱导的对阿霉素诱导毒性的保护机制是由于抑制脂质过氧化和防止GSH耗竭。

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