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Essential Metal Status, Prooxidant/Antioxidant Effects of MiADMSA in Male Rats: Age-related Effects
Authors:S J S Flora  Ashish Mehta  Pratibha Gautam  P C Jatav  Uma Pathak
Institution:(1) Department of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India;(2) Division of Synthetic Chemistry, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India
Abstract:Thiols are known to act as protectants in the biological system for their involvement in a number of metabolic regulations. In this study, we investigated the effect of a new and potent thiol-chelating agent, monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), an analog of meso 2,3-dimercaptosuccinic acid, to find out if it could act as a prooxidant (because of its lipophilic character) or antioxidant (because of thiol moiety) that could supplement its chelating properties in different age groups of male rats (young, adult, and old rats) and produce effective clinical recoveries in the treatment of metal intoxication. Animals were treated with 25, 50, and 100 mg/kg of MiADMSA, i.p, once daily for 1 week to assess the effect on the antioxidant system in major organs based on sensitive biochemical variables indicative of oxidative stress. Results suggested that MiADMSA administration increased the activity of d-aminolevulinic acid dehydratase in all the age groups and increased blood glutathione (GSH) levels in young rats. MiADMSA also potentiated the synthesis of metallothioneine in liver and kidneys and GSH levels in liver and brain. Apart from this it also significantly reduced the glutathione disulfide levels in tissues. However, administration of MiADMSA caused some concern over the copper loss. MiADMSA was found to be safe in rats of all ages.
Keywords:Chelator  MiADMSA  Age  Prooxidant  Antioxidant  Rats  Metallothioneine  Chelation therapy
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