Combined administration of iron and monoisoamyl-DMSA in the treatment of chronic arsenic intoxication in mice |
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Authors: | M Modi S J S Flora |
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Institution: | (1) Division of Pharmacology and Toxicology, Defense Research and Development Establishment, Jhansi Road, Gwalior, 474002, India |
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Abstract: | Co-administration of iron in combination with monoisoamyl dimercaptosuccinic acid (MiADMSA) against chronic arsenic poisoning
in mice was studied. Mice preexposed to arsenic (25 ppm in drinking water for 6 months) mice were treated with MiADMSA (50 mg/kg,
intraperitoneally) either alone or in combination with iron (75 or 150 mg/kg, orally) once daily for 5 days. Arsenic exposure
led to a significant depletion of blood δ-aminolevulinic acid dehydratase (ALAD) activity, hematocrit, and white blood cell
(WBC) counts accompanied by small decline in blood hemoglobin level. Hepatic reduced glutathione (GSH) level, catalase and
superoxide dismutase (SOD) activities showed a significant decrease while, oxidized glutathione (GSSG) and thiobarbituric
acid-reactive substances (TBARS) levels increased on arsenic exposure, indicating arsenic-induced hepatic oxidative stress.
Liver aspartate and alanine transaminases (AST and ALT) activities also decreased significantly on arsenic exposure. Kidney
GSH, GSSG, catalase level and SOD activities remained unchanged, while, TBARS level increased significantly following arsenic
exposure. Brain GSH, glutathione peroxidase (GPx), and SOD activities decreased, accompanied by a significant elevation of
TBARS level after chronic arsenic exposure. Treatment with MiADMSA was marginally effective in reducing ALAD activity, while
administration of iron was ineffective when given alone. Iron when co-administered with MiADMSA restored blood ALAD activity.
Administration of iron alone had no beneficial effects on hepatic oxidative stress, while in combination with MiADMSA it produced
significant decline in hepatic TBARS level compared to the individual effect of MiADMSA. Renal biochemical variables were
insensitive to any of the treatments. Combined administration of iron with MiADMSA also had no additional beneficial effect
over the individual protective effect of MiADMSA on brain oxidative stress. Interestingly, combined administration of iron
with MiADMSA provided more pronounced depletion of blood arsenic, while no additional beneficial effects on tissue arsenic
level over the individual effect of MiADMSA were noted. The results lead us to conclude that iron supplementation during chelation
has some beneficial effects particularly on heme synthesis pathway and blood arsenic concentration. |
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Keywords: | Arsenic toxicity Iron administration Biochemical and toxicological effects Oxidative stress Metal decorporation Chelation Monoisoamyl-DMSA Mouse |
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