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-hydroxydeoxyguaonsome) 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.