Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice.
Sánchez G. M., Re L., Giuliani A., Núñez-Sellés A. J., Davison G. P., León-Fernández O. S.
Author Affiliation: Centre for Research and Biological Evaluation, Pharmacy Institute, Havana University, P.O. 10 400, Havana, Cuba.
Pharmacological Research 42 : 565-573
Abstract : TPA or 12-0-tetradecanoylphorbol-13-acetate (0.1 µg) was intraperitoneally injected into mice pretreated for 7 days with Vimang (M. indica bark extract) at 50-250 mg/kg, mangiferin (100 mg/kg), ascorbic acid (100 mg/kg), vitamin E (100 mg/kg) and ?-carotene (50 mg/kg), administered orally. Treatment with vitamin E, ascorbic acid, ?-carotene, mangiferin and Vimang increased the superoxide dismutase (SOD) level in mice. TPA also increased the SOD level for all groups, with higher levels observed for mice pretreated with ?-carotene, Vimang and mangiferin. Only the Vimang-treated mice preserved glutathione peroxidase (GPx) at its normal level while other antioxidants attenuated the TPA-induced GPx depletion. In the absence of TPA, vitamin E was able to increase superoxide anion production by peritoneal macrophages, while other treatments did not significantly affect superoxide anion without TPA. Pretreatment with antioxidants reduced the TPA-induced cytochrome-c reduction in mice. The concentration of H2O2 produced by peritoneal macrophages from TPA-induced mice was increased by 2.7-fold compared with the control group. Unlike other treatments, pretreatment with Vimang inhibited, in a dose-dependent manner, the production of H2O2 induced by TPA. A 2.3- and 1.7-fold increase in DNA fragmentation in hepatic and brain tissues of mice, respectively, was induced by TPA. A significant decrease in this TPA-induced DNA fragmentation was observed after pretreatment with Vimang, mangiferin, ascorbic acid + vitamin E, or ?-carotene. Vimang demonstrated a dose-dependent inhibition of TPA-induced biomolecule oxidation. Lipid peroxidation (LP) in hepatic mitochondria, microsomes, serum and supernatant of brain homogenates increased in mice treated with TPA, ascorbic acid and vitamin E. Vimang, ?-carotene and mangiferin, however, decreased LP peroxidation. It is suggested that Vimang could be used to prevent production of ROS and oxidative tissue damage in vivo.