Chemopreventive effect of Ginkgo biloba extract against benzo(a)pyrene-induced forestomach carcinogenesis in mice: Amelioration of doxorubicin cardiotoxicity

Ginkgo biloba extract (EGb) is a natural product that possesses antioxidant and anticlastogenic properties. The current study was conducted to investi gate the effect of EGb on benzo(a)pyrene (BP)-induced forestomach neoplasia , and to explore its possible beneficial effects against doxorubicin (Dox)- induced cardiotoxicity. Tumor was induced in female Swiss albino mice by or al administration of 1 mg BP, twice weekly for four weeks. EGb was given, a t a daily oral dose of 150 mg kg(-1), two weeks before and during BP admini stration. Dox was given ip at a dose of 1.5 mg kg(-1), once weekly, for fou r weeks, during BP administration. EGb and Dox were given as combined or mo notherapies. Results of the present investigation revealed that EGb blunted forestomach tumor multiplicity, as compared to control tumor bearing group . It also exhibited high activity to induce cytosolic glutathione S-transfe rase and glucose-6-phosphate dehydrogenase (G6PDH) in liver, as well as rep lenished hepatic glutathione that have been inhibited or depleted by tumori genesis. Furthermore, it normalized nitric oxide (NO) serum level, without any observed alteration in neither the activity of liver microsomal NADPH-c ytochrome P-450 reductase nor serum level of tumor necrosis factor-alpha (T NF alpha). Similar results have been obtained with Dox, but it failed to af fect GGPDH activity, while increased semm TNF alpha and NO levels. The comb ined therapy did not add further to the anticarcinogenic effect of Dox, how ever it succeeded in ameliorating the deleterious effects of Dox on the hea rt; as evidenced by the reduction of cardiac lipoperoxidation, with modulat ion of Dox-induced pathological changes. Therefore, EGb confers a beneficia l chemopreventive effect against BP-induced gastric carcinogenesis in mice, and possesses a salutary ameliorating potential on the cardiotoxic effects of Dox.