ABSTRACT
Sunitinib (SUN) is an oral tyrosine kinase inhibitor approved in 2006 as a first-line treatment for metastatic renal cell cancer. However, weak selectivity to kinase receptors and cardiotoxicity have limited the use of sunitinib. Rivaroxaban (RIVA) is a Factor Xa inhibitor with cardioprotective action. It inhibits atherosclerosis and numerous inflammatory cascades. The present study was designed to investigate the cardioprotective effects of RIVA in sunitinib-induced cardiotoxicity. Thirty male Wistar rats were divided into five groups. Group 1 was the normal control (control). Group 2 was administered i.p. SUN 25 mg kg-1 thrice weekly for 3 weeks. Groups 3 and 4 received the same treatment as Group 2 followed by the administration of RIVA 5 mg kg-1 day-1 and 10 mg kg-1 day-1, respectively, for 3 weeks. Group 5 received only 10 mg kg-1 day-1 RIVA for 3 weeks. Serum levels of Ca2+, Mg2+, Fe3+/Fe2+, lipid profiles, and cardiac enzymes were measured. Cardiac tissues were isolated for the measurements of oxidant/antioxidant balance gene and protein expressions. Relative to the controls, the administration of SUN significantly altered serum levels of (Ca2+, Mg2+, Fe3+/Fe2+, lipid profiles, and cardiac enzymes), intracellular antioxidant enzymes, and the expression levels of the genes encoding certain proteins. RIVA treatment significantly restored these parameters to near-normal levels. RIVA treatment significantly mitigated SUN-induced cardiac injuries by restoring antioxidant enzyme levels and attenuating the proinflammatory cascades resulting from SUN-induced cardiac injuries.
