Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes.
Protective effect of various antioxidants, trolox (water soluble analogue of vitamin E), quercetin (bioflavonoid) and glutathione reduced (GSH), was studied following sulphur mustard (SM) intoxication. SM, a blistering agent was administered to Swiss albino female mice through inhalation (1 LC50=42.3 mg/m3 for 1 h duration; 14 days observation for mortality) and percutaneous (1 LD50=154.7 mg/kg; 7 days observation for mortality) routes. The antioxidants were administered three times at the dose of trolox, 500 microg/kg; quercetin, 5 mg/kg and GSH, 400 mg/kg body weight by intraperitoneal injection, one immediately following SM exposure, then once each day for 2 days after SM treatment. The effect of antioxidants on survival, markers of oxidative damage and purine metabolites was investigated. Survival study animals were observed for 14 days. Oxidative markers (in blood, liver and lung) and purine metabolites (in blood and urine) were investigated 72 h after SM treatment. Survival time increased significantly following trolox and quercetin treatments through the inhalation route. Significant decrease in GSH and increase in the level of malondialdehyde (MDA) indicated oxidative damage to liver and lung tissues following SM inhalation and percutaneous exposure. Blood and urinary uric acid, end product of purine metabolism showed an increased following both routes of exposures. The antioxidants, trolox and quercetin protected the liver and lung tissues from oxidative damage caused by SM exposure through inhalation and percutaneous routes. This study showed that antioxidants could enhance survival time, protect liver and lung from oxidative damage and reduce accumulation of purine metabolites in blood following SM intoxication.
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, 474002, Gwalior, India. drde@gwrl.dot.net.in
O
O
Kumar
K
K
Sugendran
R
R
Vijayaraghavan
D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D002839:Chromans / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity*; D011794:Quercetin / Q000008:administration & dosage; D015996:Survival Rate; D014527:Uric Acid / Q000097:blood / Q000652:urine
D000975:Antioxidants; D002839:Chromans; D014527:Uric Acid; D008315:Malondialdehyde; D011794:Quercetin; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D009151:Mustard Gas