Cisplatin-induced cardiotoxicity Mechanisms and cardioprotective strategies
Cisplatin-induced cardiotoxicity Mechanisms and cardioprotective strategies
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DOI：
10.1016/j.ejphar.2010.09.085
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发表时间：
2011-01-10
影响因子：
5
通讯作者：
Radwan, Asmaa
中科院分区：
文献类型：
--
作者：
El-Awady, El-Sayed E.;Moustafa, Yasser M.;Radwan, Asmaa
增加氧化应激和细胞凋亡涉及的毒性,限制了临床使用顺铂作为抗tumoral药我们的研究进行了评估的防护潜力乙醯左旋肉碱DL-alpha-lipoic酸和水飞蓟素对心肌损伤cisplatin-induced八十名男性白化病老鼠分成八组第一个四组与生理盐水治疗乙醯左旋肉碱(500毫克/公斤我p) DL-a-lipoic酸(100毫克/公斤p o)其余各组分别给予相同剂量的生理盐水乙酰氨基甲酸乙酯- DL -硫辛酸和水飞蓟素，连续10 d。在单剂量顺铂（10 mg/kg / p）之前和之后，测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同功酶MB （CK-MB）活性和血浆心肌肌钙蛋白i （cTnl）浓度。顺铂治疗大鼠血清LDH、CK、CK- mb活性和cTnl血浆浓度显著升高，同时血清MDA水平显著升高，GSH含量、SOD活性和总蛋白含量显著降低然而乙酰肉碱li - α -硫辛酸和水飞蓟素显著减轻了顺铂引起的上述参数的干扰。总之，前两种药物被证明是改善顺铂诱导的心脏毒性的潜在候选药物(C) 2010 Elsevier B V All rights reserved
Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity that limits the clinical use of cisplatin as an anti tumoral drug Our study was conducted to evaluate the protective potential of acetyl-L-carnitine DL-alpha-lipoic acid and silymarin against cisplatin-induced myocardial injury Eighty male albino rats were divided into eight groups The first four groups were treated with normal saline acetyl-L-carnitine (500 mg/kg i p) DL-a-lipoic acid (100 mg/kg p o) and silymarin (100 mg/kg p o) respectively for 10 successive days The remaining groups were treated with the same doses of normal saline acetyl i carnine DL alpha-lipoic acid and silymarin respectively for 5 successive days before and after a single dose of cisplatin (10 mg/kg i p) Serum activities of lactate dehydrogenase (LDH) creatine kinase (CK) creatine kinase isoenzyme MB (CK-MB) and plasma cardiac troponin I (cTnl) concentration were estimated Malondialde hyde (MDA) reduced glutathione (GSH) contents superoxide dismutase activity (SOD) and protein content in cardiac tissues were measured Moreover integrity of both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) was also examined Cisplatin treated rats experienced a significant elevation of serum activities of LDH CK CK-MB and cTnl plasma concentration These effects were accompanied by a significant increase in MDA level On the other hand a significant decrease in GSH content SOD activity and total protein content was observed In addition both mtDNA and nDNA were heavily damaged However acetyl-carnitine DI-alpha-lipoic acid and silymarin significantly attenuated the cisplatin-evoked disturbances in the above mentioned parameters In conclusion the former drugs were proven to be potential candidates to ameliorate cisplatin induced cardiotoxicity (C) 2010 Elsevier B V All rights reserved