Suppression of Doxorubicin Apoptotic, Histopathologic, Mutagenic and Oxidative Stress Effects in Male Mice Bone Marrow and Testis Tissues by Aqueous Rosemary Leaves Extract

In the present set of investigations, the anti-mutagenic and anti-cytotoxic effects of aqueous rosemary leaves extract (RE) beside the dose dependency of these effects on male mice bone marrow and germ cells have been evaluated using in vivo cytogenetic, histopathologic and apoptotic assays, as well as biochemical analysis. Doxorubicin (DXR), a well-known mutagen and cytotoxic agent, was given at a single dose of 25 mg/kg b. wt. intraperitoneally at the fifteenth day. 25, 125, 250 and 375 mg/kg b. wt. of RE were given through oral intubation once a day/three days for 15 days prior to DXR administration. The animals of the positive control group (DXR alone) showed significant increase in the mutagenic effect in bone marrow cells, histological damage, incidence of apoptotic cells (TUNEL-positive cells), level of lipid peroxidation and activity of superoxide dismutase in testis. Though, the activities of the other antioxidant enzymes such as glutathione peroxidase, catalase and glutathione reduced form beside the serum level of testosterone and the rate of primary spermatocytes' transformation to spermatids were significantly declined (P< 0.001). The ratio of dismutase to glutathione peroxidase and/or catalase was significantly elevated. Pretreatment with each dose of RE showed significant reduction in these frequency of chromosomal aberrations and mitotic index of bone marrow cells and the level of peroxidation, the ratio of SOD/ GPX or CAT, the histological damage and the incidence of apoptotic cells in testes. Also, it caused increase in the levels of some antioxidant enzymes (GSH, CAT and GPX), the level of testosterone and returned the semineferous tubular cell populations' ratio to the control distribution.The protective efficacy of the RE was much pronounced following pretreatment with 125 mg/kg b. wt.