Meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA effect on gallium arsenide induced pathological liver injury in rats.
The effect of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) on gallium arsenide (GaAs) induced liver damage was studied. The oral feeding rat model was used in this study. The animals were exposed to 10 mg/kg GaAs, orally, once daily, 5 days a week for 24 weeks and treated thereafter with single oral daily dose of either 0.3 mmol/kg DMSA or MiADMSA for two course of 5 days treatment. The animals were sacrificed thereafter. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substance (TBARS). Liver damage was assessed by number of biochemical variables and by light microscopy. The activity of superoxide dismutase (SOD) and delta-aminolevulinic acid dehydratase (ALAD) beside reduced glutathione (GSH) concentration was measured in blood. Exposure to GaAs produced a significant reduction in GSH while, increased the oxidized glutathione (GSSG) concentration. Hepatic glutathione peroxidase (GPx) and catalase activity increased significantly while level of serum transaminase increased moderately. Gallium arsenide exposure also produced marked hepatic histopathological lesions. Overall, treatment with MiADMSA proved to be better than DMSA in the mobilization of arsenic and in the turnover of some of the above mentioned GaAs sensitive biochemical alterations. Histopathological lesions also, responded more favorably to chelation treatment with MiADMSA than DMSA.
Flora
S J S
SJ
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Raod, 474 002, Gwalior, India. sjsflora@hotmail.com
Dubey
Rupa
R
Kannan
G M
GM
Chauhan
R S
RS
Pant
B P
BP
Jaiswal
D K
DK
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001152:Arsenicals / Q000037:antagonists & inhibitors*; D001219:Aspartate Aminotransferases / Q000097:blood; D002374:Catalase / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D005708:Gallium / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D008670:Metals / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D000623:Porphobilinogen Synthase / Q000097:blood; D051381:Rats; D004113:Succimer / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D001152:Arsenicals; D002614:Chelating Agents; D008670:Metals; C043055:gallium arsenide; C091888:monoisoamyl-2,3-dimercaptosuccinate; D005708:Gallium; D004113:Succimer; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000623:Porphobilinogen Synthase; D005978:Glutathione