Quercetin augments the protective effect of losartan against chronic doxorubicin cardiotoxicity in rats

Abstract

The present study aimed to examine whether the co-administration of quercetin (QRN) and losartan (LOS) can produce additional protective effects against chronic DOX cardiotoxicity. Cardiotoxicity in rats was induced by intraperitoneal injection of doxorubicin (DOX) in a cumulative dose of 15mg/kg for two weeks. Results revealed that DOX administration exhibited elevated serum levels of TNF-α, creatine kinase (CK-MB), lactate dehydrogenase (LDH) in addition to increased myocardial lipid peroxide (MDA) and nitric oxide (NO) alongside attenuating cardiac antioxidant defense system of superoxide dismutase (SOD) and catalase (CAT) activities. DOX produced leukocyte infiltration and myocardial lesions. Pretreatment with QRN (10mg/kg, orally) solely or in combination with LOS (0.7mg/kg, orally) for 6 weeks markedly ameliorated all these biochemical characteristics, and substantially reduced the myocardium peroxidative damage. The protective effects obtained by LOS were more pronounced by its combination with QRN. Our results suggest that quercetin potentially augmented the cardioprotective effect of losartan against chronic DOX cardiotoxicity via its antioxidant and anti-inflammatory properties.

Keywords: Cardiotoxicity; Doxorubicin; Losartan; Oxidative stress; Quercetin; TNF-α.