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Protective Effects of Olmesartan and L-carnitine on Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin (DOX), anthracycline antibiotic, is an important antineoplastic agent due to its high antitumor efficacy in hematological, as well as in solid malignancies. The present study aimed to investigate the possible protective effect of olmesartan (Olm), L-carnitine (L-CA) and their combination in cardiotoxicity induced by doxorubicin (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 results, DOX showed a significant elevation in serum troponin I, CK-MB, and LDH, together with increased inflammation manifested by the rise of TNF-α, ICAM-1, IL-1, MPO, NF-k β and TGF-β in cardiac tissues. While, DOX-induced oxidative stress by increasing in MDA and decreasing in SOD and 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 above mentioned 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 confirms the protective role of L-CA and Olm in DOX-induced cardiotoxicity.