Essential metal status, prooxidant/antioxidant effects of MiADMSA in male rats: age-related effects.
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.
Flora
S J S
SJ
Department of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, India. sjsflora@hotmail.com
Mehta
Ashish
A
Gautam
Pratibha
P
Jatav
P C
PC
Pathak
Uma
U
D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000097:blood; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000097:blood; D008274:Magnesium / Q000097:blood; D008297:Male; D008670:Metals / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000097:blood; D011524:Protoporphyrins / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D015032:Zinc / Q000097:blood
D000975:Antioxidants; D002614:Chelating Agents; D006454:Hemoglobins; D008670:Metals; D016877:Oxidants; D011524:Protoporphyrins; D017392:Thiobarbituric Acid Reactive Substances; C017803:zinc protoporphyrin; D003300:Copper; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D007501:Iron; D013482:Superoxide Dismutase; D000623:Porphobilinogen Synthase; D005978:Glutathione; D008274:Magnesium; D015032:Zinc; D019803:Glutathione Disulfide