Phosphine-induced oxidative damage in rats: Role of glutathione

Phosphine (PH₃), generated from aluminium, magnesium and zinc phosphide, is a widely used pesticide. PH₃ induces oxidative stress in insects, mammalian cells, animals, and humans. The involvement of glutathione (GSH) in PH₃-induced oxidative toxicity is controversial. GSH levels in various tested tissues were reduced in aluminium phosphide-poisoned rats and humans, while the levels remained unchanged in insects and mammalian cells. This study examines the effectiveness of endogenous GSH as a protective agent against PH₃-induced oxidative damage in rats. The association of PH₃-induced nephrotoxicity and cardiotoxicity with free radical production was also tested. Male Wistar rats, administered intraperitoneally (I.P.) with PH₃ at 4 mg/kg, were evaluated 30 min after treatment for PH₃ toxicity to organs. PH₃ significantly decreased GSH, GSH peroxidase and catalase, while significantly increased lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals), DNA oxidation (as 8-hydroxydeoxyguaonsoine) and superoxide dismutase (SOD) levels in kidney and heart. These changes were significantly alleviated by melatonin (10 mg/kg I.P., 30 min before PH₃), with the exception of SOD activity in heart tissue. The study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH₃) significantly enhanced the effect of PH₃ on GSH loss and lipid peroxidation elevation in lung. These findings indicate that (1) endogenous GSH plays a crucial role as a protective factor in modulating PH₃-induced oxidative damage, and (2) PH₃ could injure kidney and heart (as noted earlier with brain, liver and lung) via oxidative stress and the antioxidant melatonin effectively prevents the damage.