Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Eur J Pharmacol. 2011 Jan 10;650(1):335-41. doi: 10.1016/j.ejphar.2010.09.085. Epub 2010 Oct 29.
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-α-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 (500mg/kg, i.p.), DL-α-lipoic acid (100mg/kg, p.o.) and silymarin (100mg/kg, p.o.) respectively, for 10 successive days. The remaining groups were treated with the same doses of normal saline, acetyl-l-carnitine, DL-α-lipoic acid and silymarin, respectively, for 5 successive days before and after a single dose of cisplatin (10mg/kg, i.p.). Serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and plasma cardiac troponin I (cTnI) concentration were estimated. Malondialdehyde (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 cTnI 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-l-carnitine, DL-α-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.
氧化应激和细胞凋亡增加与顺铂作为抗肿瘤药物的临床应用受限的心脏毒性有关。本研究旨在评估乙酰左旋肉碱、DL-α-硫辛酸和水飞蓟素对顺铂诱导的心肌损伤的保护作用。80 只雄性白化大鼠被分为 8 组。前 4 组分别用生理盐水、乙酰左旋肉碱（500mg/kg，ip）、DL-α-硫辛酸（100mg/kg，po）和水飞蓟素（100mg/kg，po）连续治疗 10 天。其余 4 组分别用相同剂量的生理盐水、乙酰左旋肉碱、DL-α-硫辛酸和水飞蓟素连续治疗 5 天，然后单次腹腔注射顺铂（10mg/kg）。测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶 MB（CK-MB）和血浆心肌肌钙蛋白 I（cTnI）浓度。测定丙二醛（MDA）、还原型谷胱甘肽（GSH）含量、超氧化物歧化酶活性（SOD）和心脏组织蛋白含量。此外，还检查了线粒体 DNA（mtDNA）和核 DNA（nDNA）的完整性。顺铂处理的大鼠血清 LDH、CK、CK-MB 和 cTnI 血浆浓度显著升高。这些作用伴随着 MDA 水平的显著升高。另一方面，GSH 含量、SOD 活性和总蛋白含量显著降低。此外，mtDNA 和 nDNA 均受到严重损伤。然而，乙酰左旋肉碱、DL-α-硫辛酸和水飞蓟素显著减轻了顺铂引起的上述参数的紊乱。总之，这些药物被证明是改善顺铂诱导的心脏毒性的潜在候选药物。
