A Drosophila model for the screening of bioavailable NADPH oxidase inhibitors and antioxidants.

NADPH oxidase is the major source of non-mitochondrial cellular reactive oxygen species (ROS), and also is reported to be a major cause of various diseases including atherosclerosis and hypertension. In order to screen a new curative reagent that can suppress NADPH oxidase activity, we developed a Drosophila melanogaster fly that would overexpress human Dual oxidase 2 (hDuox2), a member of the NADPH oxidase family, as a screening model. These flies (GMR-GAL4/UAS-hDuox2) had a high generation of ROS in the posterior region of the eye discs along with an easily recognizable rough-eye phenotype, which is an ideal and convenient marker for further screening steps. Moreover, the hDuox2-induced rough-eye phenotype can be rescued by feeding with a culture medium containing mulberry leaves (MLs), which reportedly have an antimetabolic effect. Some commercially available antioxidants such as quercetin-3-O-D-glucoside or quercetin-3-O-glucose-6''-acetate, or the naringin contained in MLs and other herbs, also have shown a similar suppressing effect on the rough-eye phenotype. Our results suggest that flavonoid glycoside is absorbed from the intestine and functions in the body of D. melanogaster as it does in mammalian models such as rats. Thus, the GMR-GAL4/UAS-hDuox2 fly line is a promising model for the screening of novel drugs such as NADPH oxidase inhibitors and/or antioxidants.