Antioxidant, anti-inflammatory and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats

Abstract Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malgnencies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. The present study analyzed the effects of crocin on doxorubicin’s cardiotoxic efect in rat myocardium and searched their mechanistic interaction in the pathogenesis of DOX-induced myocardial toxicity. Forty rats were divided into four groups; (a) control (received normal saline as a dose of 1 ml/kg by ip for 15 days), (b) Crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX + Crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection and crocin as a dose of 40 mg/kg/24h ip for 15 days). According to the present study, DOX administration caused significant increases in lipid indices (triglyseride, low-dencity lipoproteins and very low-dencity lipoproteins) as well as cardiac markers (Creatine kinase-muscle/brain and Cardiac Troponin I). Morever, DOX caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status) as well as decreases in antioxidant defense systems (glutathione, superoxide dismutase, catalase and total antioxidant status). The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile and biochemical parameters in rats receiving DOX. The results were supported by histopathological and immunohistochemical evaluations. Taken together, our results reveal that crocin might be a cardioprotective agent in DOX treated patients for cancer.