A role for glutathione, independent of oxidative stress, in the developmental toxicity of methanol.

摘要: Abstract Oxidative stress and reactive oxygen species (ROS) have been implicated in the teratogenicity of methanol (MeOH) rodents, both vivo embryo culture. We explored ROS hypothesis further pregnant C57BL/6J mice. Following maternal treatment with a teratogenic dose MeOH, 4 g/kg via intraperitoneal (ip) injection on gestational day (GD) 12, there was no increase 6 h later embryonic formation, measured by 2′,7′-dichlorodihydrofluorescin diacetate (DCFH-DA) fluorescence, despite an observed positive control ethanol (EtOH), nor oxidatively damaged DNA, quantified as 8-oxo-2′-deoxyguanosine (8-oxodG) formation. MeOH (primarily ophthalmic anomalies, cleft palate) also not altered pre- post-treatment varying doses free radical spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN). In contrast, pretreatment l -buthionine-(S,R)-sulfoximine (BSO), inhibitor glutathione (GSH) synthesis, depleted hepatic GSH, enhanced some new anomalies (micrognathia, agnathia, short snout, fused digits, lip, low set ears), but most common effects (ophthalmic this strain. These results suggest that did contribute to mouse model, contrast culture from our laboratory, protective effect GSH model may arise its role cofactor for formaldehyde dehydrogenase detoxification formaldehyde.