Phosphine-induced oxidative damage in rats: role of glutathione.
Phosphine (PH(3)), generated from aluminium, magnesium and zinc phosphide, is a widely used pesticide. PH(3) induces oxidative stress in insects, mammalian cells, animals, and humans. The involvement of glutathione (GSH) in PH(3)-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 PH(3)-induced oxidative damage in rats. The association of PH(3)-induced nephrotoxicity and cardiotoxicity with free radical production was also tested. Male Wistar rats, administered intraperitoneally (I.P.) with PH(3) at 4 mg/kg, were evaluated 30 min after treatment for PH(3) toxicity to organs. PH(3) 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 PH(3)), with the exception of SOD activity in heart tissue. The study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH(3)) significantly enhanced the effect of PH(3) 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 PH(3)-induced oxidative damage, and (2) PH(3) could injure kidney and heart (as noted earlier with brain, liver and lung) via oxidative stress and the antioxidant melatonin effectively prevents the damage.
Hsu
Ching-Hung
CH
Department of Public Health, School of Medicine, Taipei Medical University, Taipei, Taiwan. chsu@oehha.ca.gov
Chi
Bei-Ching
BC
Liu
Ming-Yie
MY
Li
Jih-Heng
JH
Chen
Chiou-Jong
CJ
Chen
Ruey-Yu
RY
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010720:Phosphines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000963:Antimetabolites; D000975:Antioxidants; D010720:Phosphines; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D005978:Glutathione; D008550:Melatonin