Phosphine-induced oxidative damage in rats: attenuation by melatonin

Phosphine (PH3), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH3-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH3-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH3 at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH3 caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36–42%), lung (32–38%) and liver (19–25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH3 were melatonin, vitamin C, and β-carotene at 10, 30, and 6 mg/kg, respectively. The PH3-induced changes were significantly or completely blocked by melatonin while vitamin C and β-carotene were less effective or inactive. These findings establish that PH3 induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH3.