Modulatory effects of rosemary leaves aqueous extract on doxorubicin-induced histological lesions, apoptosis and oxidative stress in mice

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. 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. 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. 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

Antimutagenic activity of egyptian propolis and bee pollen water extracts against cisplatin-induced chromosomal abnormalities in bone marrow cells of mice

Bee-collected pollen and propolis are apicultural products which are recognized as a well balanced food. These beehive products are composed of nutritionally valuable substances and contain considerable amounts of polyphenol substances which may have several useful pharmacological properties. The protective activity of Bee-collected pollen [BPE] and water-soluble derivative of propolis [WSDPE] aqueous extracts was studied on cisplatin[CDDP] induced genotoxicity in male albino mice [Mus mascullus]. The treatment of mice with Bee-collected pollen and propolis extracts at doses 140 and 8.4 mg/kg body weight/day, respectively for 14 days synergistically with the intraperitoneal administration of cisplatin at dose of 2.8 mg/kg b.wt exhibited significant chemoprotective activity. Genotoxicity and cytotoxicity was evaluated by the bone marrow chromosomal aberration assay and mitotic index, respectively. WSDPE and BPE, alone did not significantly induce chromosomal aberrations confirming their non-mutagenic effects. While, the animals in groups five and six [G5 and G6], that were injected i.p. with CDDP alone for one week and then for the next 14 days these animals were given WSDPE and BPE in synergistic with i.p. injection of CDDP, exhibited a significant decrease in cytogenetic damages induced by CDDP in bone marrow cells. The anti-cytotoxicity effects of WSDPE and BPE were also evident, as observed by significant increase in mitotic index, when compared to positive control group [G2]. Thus, results of the present investigation revealed that WSDP and BPE have chemoprotective potential against CDDP induced genotoxicity in bone marrow cells of male albino mice. Also, the present investigation indicated that the chemoprotective frequency of BPE was much greater than WSDPE

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