Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats

Abstract

Doxorubicin (DOX), an anthracycline antibiotic, is an important antineoplastic agent due to its high antitumor efficacy in hematological as well as in solid malignancies. The clinical use of DOX is limited due to its cardiotoxic effects. The present study aimed to investigate the possible protective effect of olmesartan (Olm), l-carnitine (L-CA), and their combination in cardiotoxicity induced by DOX in rats. Male albino rats were randomly divided into seven experimental groups (n = 8): group I: normal control, group II: L-CA, group III: Olm, group IV: DOX. The other three groups were treated with Olm (10 mg/kg), L-CA (300 mg/kg), and their combination for 2 weeks after induction of cardiotoxicity by a single dose of DOX (20 mg/kg). In the results, DOX showed a significant elevation in serum troponin I, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) together with increased inflammation manifested by the rise of tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecules-1 (ICAM-1), interleukin IL-1β (IL-1β), myeloperoxidase (MPO), nuclear factor-kappa B (NF-κB), and transforming growth factor beta (TGF-β) in cardiac tissues as well as DOX-induced oxidative stress by increasing in malondialdehyde (MDA) and decreasing in superoxide dismutase (SOD) and glutathione (GSH) in heart tissues. In addition, caspase-3 activity was boosted as indication of increased apoptosis. On the other hand, administration of L-CA and Olm attenuated the DOX-evoked disturbances in the abovementioned parameters. In addition, DOX exhibited echocardiographic changes and severe histopathological changes, which were significantly reversed by L-CA and Olm treatment. In conclusion, the present study data confirm the protective role of L-CA and Olm in DOX-induced cardiotoxicity, which may be related to its antioxidant, antiinflammatory, and antiapoptotic agents.