| Reactive oxygen species (ROS) play an important role in the pathogenesis of some human diseases, particularly in cardiovascular disease, nerve degenerative disease, and cancer Oxidative stress, as a result of ROS overload, can elicit many deleterious effects on biological macromolecules such as phospholipids, protein and DNA. For example, ROS can cause various oxidative DNA damages including base modification, base loss and single and double strand breaks. Failure of complete repair of DNA damage may give rise to point mutation as well as cancer initiation. And also, the adverse effects of some drugs such as bleomycin and doxorubicin (DOX ) are closely related with ROS, which may be produced in the process of drug metabolism. For example, free radical damage has been well known in DOX-induced cardiotoxicity. There is growing evidence that antioxidants hold great promise in preventing or even curing some ROS-related human disorders. FLZ-52A is a synthetic compound which has been proved to be a highly efficient scavenger of both superoxide and hydroxyl free radicals. EGb761, a stringently standardized extract from Ginkgo biloba leaves(IPSEN, Paris), mainly contains flavonoid substances and terpenoids, which also have antioxidant activities. The aims of this paper were to study the protective effects of FLZ-52A and EGb761 on DOX-induced cardiotoxicity and their active mechanisms. In addition, the effects of FLZ-52A on hydrogen peroxide-mediated cell transformation of Balb/3T3 and DNA damage were also studied.1. Protective effects of FLZ-52A and EGb761 on DOX- induced cardiotoxicityThe protection of FLZ-52A and EGb761 against DOX-induced cardiotoxicity was studied with isolated rat heart mitochondria, primarily cultured neonatal rat heart myocytes and in mice . The other important goal of this study was to test whether FLZ-52A and EGb761 have any effect on the antitumor property of DOX.In in vitro experiments of isolated rat heart mitochondria, 10-5 mol/L DOX in the presence of10-5 mol/L ferrous sulfate significantly stimulated malondialdehyde(MDA) production and reducedATPase activity of rat heart mitochondria. Prior addition of various concentrations of FLZ-52A(10-6, 10-5, 10-4 mol/L) or EGb761(5,10,15,30μg/mL) to the incubation mixture prevented...
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