Ameliorating effect of DL-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals

Abstract

Cisplatin is a potent chemotherapeutic agent with a wide range of activities. Nephrotoxicity and cardiotoxicity represent it's major complication upon clinical use. The present study was carried out to evaluate the possible protective effect of DL-α-lipoic acid (LA) against cisplatin-induced nephrotoxicity and cardiotoxicity. Different groups of rats (n = 10) were administered either saline (control), cisplatin (10 mg/kg, i.p.), LA (100 mg/kg, i.p.) or their combination (LA 30 min prior to cisplatin administration). Twenty-four hours later all animals were decapitated and sera were used for estimation of activities of urea (BUN), creatinine (Cr), lactate dehydrogenase (LDH), and creatine kinase (CK). Homogenates of the kidney and heart were used for estimation of oxidative stress markers (reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO)). Additionally, caspase-3 activities and DNA-fragmentation were investigated in renal tissues. The results showed that cisplatin produced significant elevation in serum activities of LDH, CK, BUN, and Cr and also induced significant elevation in the oxidative stress makers (MDA and NO) accompanied by significant reduction in GSH and SOD in both kidney and heart. The integrity of DNA was heavily damaged and caspase-3 was activated in renal tissues. The results emphasized nephrotoxicty and cardiotoxicity of cisplatin. On the other hand, prior administration of LA significantly attenuated the cisplatin-evoked disturbances in the above mentioned parameters and protected both kidney and heart tissues. The histopathological examination emphasized the obtained results. In conclusion, LA is suggested to be a potential candidate to ameliorate cisplatin-induced nephrotoxicity and cardiotoxicity without altering the antitumor efficacy of cisplatin.