Rosemary Leaves Aqueous Extract for Protection against Acute Doxorubicin-Induced Cardiotoxicity in Mice

Abstract

Doxorubicin (DOX) is a cancer chemotherapy widely used to treat a many types of human malignancies, DOX is potent anthracycline antibiotic. As a complicating effect of DOX cardiotoxicity has long been recognized; To explain this cardiotoxicity there are several hypotheses and the most thoroughly investigated one is free radical hypothesis. Our study was designed to investigate if the aqueous extract of rosemary leaves has a protective effect against cardiotoxicity induced by DOX in mice. Twenty eight male Swiss Albino mice were randomly divided into four groups including group1 (negative control), treated with distill water (D.W), group 2 (positive control), treated with 15 mg/kg DOX as a single intraperitoneal (i.p) injection, groups 3 and 4 received 15mg/kg and 30mg/kg respectively of the aqueous extract of Rosmarinus officinalis leaves (ROE) orally (p.o), once daily for 2 weeks, then injected i.p with 15 mg/kg DOX. Two days after DOX or D.W (in control group) injection, animals in all groups were scarified and the levels of the cardiac biomarkers including serum creatine kinase (CK-MB) and serum lactate dehydrogenase (LDH) were measured. Also the cardiac histopathological sections were prepared, stained by hematoxylin and eosin stains and examind under light microscope.The administration of 15mg/kg DOX caused cardiomyopathy which was manifested by extremely significant elevation (p<0.001) in serum CK-MB and LDH levels. In addition, cardiac histopathological sections showed moderate cytoplasm vacuolization and inflammatory cells infiltrate with vascular congestion. Oral administration of 30mg/kg ROE for 2 weeks prior to DOX provided significant protection which was evidenced by extremely significant reduction (p<0.001) in the levels of CK-MB and LDH. Moreover, histopathological sections revealed only mild cytoplasm vacuolization, infiltration of inflammatory cells and vascular congestion in comparison to DOX positive control group (p<0.01). Whereas oral administration of 15mg/kg ROE for 2 weeks prior to DOX showed no significant protection neither in CK-MB and LDH levels, nor in the histopathological sections. Administration of 30mg/kg ROE protect against DOX-induced cardiotoxicity. This might serve as novel adjuvant therapy with DOX.