Cisplatin-induced cardiotoxicity Mechanisms and cardioprotective strategies

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