Modulatory Effects of Rosemary Leaves Aqueous Extract on Doxorubicin‐Induced Histological Lesions, Apoptosis and Oxidative Stress in Mice

Background: Doxorubicin is used in treatment of many solid malignancies and lymphomas with poorly understood mechanism underlying tissue injury. Rosemary leaves or extracts were found to contain high antioxidant activity almost equivalent to BHA (Butylated Hydroxy Anesole) and BHT (Butylated Hydroxy Toluene). Thus, the possibility of aqueous rosemary leaves extract (RE) to ameliorate doxorubicininduced histological lesions, apoptosis and oxidative stress in male mice tissues was tested. Methods: Four doses (25, 125, 250 and 375 mg/kg b. wt.) of RE have used orally two times/ week for 15 days prior to the administration of an intraperitoneal single dose of doxorubicin (25 mg/kg b. wt.). Biochemical, histological and immunohistochemical methods were performed on liver, kidney and heart tissue sections. Results: The positive control group (DXR alone) showed severe histological lesions in the liver, kidneys and heart, including degeneration and inflammatory response accompanied with significant increase in the apoptotic index (Bax/ Bcl-2) and oxidative stress. Rosemary extract was proved to significantly attenuate the doxorubicin-related toxic effects via more than one mechanism such as: the powerful inhibition of lipid per-oxidation, the stimulation of the synthesis of cellular antioxidants, the decrease of the inflammatory response and the reduction of the apoptotic index. Conclusion: The efficacy of the tested doses of RE in improving doxorubicindeteriorated effects was organ specific. The most potent dose of RE to abate the lesions in all examined tissues , was 125mg/ kg b. wt and the less effective was 375 mg/ kg b. wt.