Paraquat toxicity and oxidative damage. Reduction by melatonin.
The ability of melatonin to protect against paraquat-induced oxidative damage in rat lung, liver, and serum was examined. Changes in the levels of malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) and reduced and oxidized glutathione concentrations were measured. Paraquat (50 mg/kg) was injected i.p. into either Sprague-Dawley or Wistar rats with or without the co-administration of 5 mg/kg melatonin. Paraquat alone increased MDA + 4-HDA levels in serum and lungs of both rat strains, with these increases being abolished by melatonin co-treatment. Paraquat also decreased reduced glutathione levels and increased oxidized glutathione concentrations in lung and liver; these changes were negated by melatonin. The effect of melatonin on paraquat-induced mortality was also studied. Paraquat at a dose of 79 mg/kg was lethal for 50% of animals within 24 hr; when administered together with melatonin, the LD50 for paraquat increased to 251 mg/kg.
Melchiorri
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D
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284-7762, USA.
Reiter
R J
RJ
Sewerynek
E
E
Hara
M
M
Chen
L
L
Nisticò
G
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis; D019803:Glutathione Disulfide; D006540:Herbicides / Q000633:toxicity*; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D008550:Melatonin / Q000494:pharmacology; D018384:Oxidative Stress; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000975:Antioxidants; D006540:Herbicides; D008315:Malondialdehyde; D005978:Glutathione; D008550:Melatonin; D010269:Paraquat; D019803:Glutathione Disulfide