Chronic arsenic poisoning in the rat: treatment with combined administration of succimers and an antioxidant.
The influence of the coadministration of vitamin C or vitamin E on the efficacy of two thiol chelators, meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA, in counteracting chronic arsenic toxicity was investigated in rats. Vitamin C and vitamin E were only mildly effective when given alone or in combination with the above chelators in mobilizing arsenic from the target tissues. However, combined administration of vitamin C plus DMSA and vitamin E plus MiADMSA led to a more pronounced depletion of brain arsenic. The supplementation of vitamins was significantly effective in restoring inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) oxidative stress in liver, kidneys, and brain as reflected by reduced levels of thiobarbituric acid reactive substance and oxidized and reduced glutathione levels. The results thus lead us to suggest that coadministration of vitamin E or vitamin C may be useful in the restoration of altered biochemical variables (particularly the effects on heme biosynthesis and oxidative injury) although it has only a limited role in depleting arsenic burden.
Kannan
Gurusamy M
GM
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, India.
Flora
Swaran J S
SJ
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001151:Arsenic / Q000493:pharmacokinetics*; D020261:Arsenic Poisoning / Q000188:drug therapy* / Q000662:veterinary*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001923:Brain Chemistry; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006418:Heme / Q000096:biosynthesis; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014018:Tissue Distribution
D000975:Antioxidants; D002614:Chelating Agents; D006418:Heme; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D001151:Arsenic; D001205:Ascorbic Acid