In Vivo and In Vitro Protective Effects of Rosmarinic Acid against Doxorubicin-Induced Cardiotoxicity

Abstract

Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects. This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments. Male rats were randomized on 7 groups: (1) control, (2) DOX (2 mg/kg, per 48 h, 12d, i.p), (3) RA (40 mg/kg, 12d, i.p.), (4–6) RA (10, 20, 40 mg/kg, 16d, i.p.)+ DOX, (7) Vitamin E (200 mg/kg, per 48 h, 16d, i.p.) + DOX and then indices of cardiac function were estimated. Also, DOX and rosmarinic acid effects were examined on MCF7 cells (breast cancer cells line) to clarify that both cardiotoxicity and anticancer effects were analyzed. DOX increased heart to body weight ratio, RRI, QA, STI, QRS duration and voltage, attenuated HR, blood pressure, Max dP/dt, Min dP/dt, LVDP, enhanced MDA, declined GSH amount, and caused fibrosis and necrosis in cardiac tissue. Administration of RA ameliorated the toxic effects of DOX. In vitro studies showed that RA did not affect the cytotoxic effect of DOX. RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.

This work was supported by the Pharmaceutical Research Center and the Vice-Chancellor of Research, Mashhad University of Medical Sciences (Grant no: 951150)

Disclosure statement

We declare that we have no conflicts of interest.

Authors contribution

Prof. Hosseinzadeh: Conceived the presented idea, developed the theory, encouraged others to investigate, and supervised the findings of this work. Dr. Razavi: Supervised the students and checked the process and findings of the experiment. Dr. Rameshrad: Wrote the proposal, carried out the hemodynamic procedure. Dr. Ghasemzadeh Rahbardar: Carried out the experiment, performed the analytic calculations and wrote the manuscript with support from Prof. Hosseinzadeh and Dr. Razavi. Mr. Eisvand: Carried out the in vitro experiment and performed the analytic calculations of this part.