Abstract
Phosphine (PH 3), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH 3-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH 3-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH 3 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. PH 3 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 PH 3 were melatonin, vitamin C, and β-carotene at 10, 30, and 6 mg/kg, respectively. The PH 3-induced changes were significantly or completely blocked by melatonin while vitamin C and β-carotene were less effective or inactive. These findings establish that PH 3 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 PH 3.
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