Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats.

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Flora SJ, Kannan GM, Pant BP, Jaiswal DK

Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats.

Arch Toxicol. 2002 Jun;76(5-6):269-76. Epub 2002 Apr 23.

PubMed ID

12107644 [ View in PubMed

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Abstract

Gallium arsenide (GaAs), a group III-VA intermetallic semiconductor, possesses superior electronic and optical properties and has a wide application in the electronics industry. Exposure to GaAs in the semiconductor industry is a potential occupational hazard because cleaning and slicing GaAs ingots to yield the desired wafer could generate GaAs particles. The ability of GaAs to induce oxidative stress has not yet been reported. The present study reports the role of oxidative stress in GaAs-induced haematological and liver disorders and its possible reversal overturn by administration of meso-2,3-dimercaptosuccinic acid (DMSA) and one of its analogue, monoisoamyl DMSA (MiADMSA), either individually or in combination with oxalic acid. While DMSA and MiADMSA are potential arsenic chelators, oxalic acid is reported to be an effective gallium chelator. Male rats were exposed to 10 mg/kg GaAs orally, 5 days a week for 8 weeks. GaAs exposure was then stopped and rats were given a 0.5 mmol/kg dose of succimers (DMSA or MiADMSA), oxalic acid or a combination of the two, intraperitoneally once daily for 5 consecutive days. We found a significant fall in blood delta-aminolevulinic acid dehydratase (ALAD) activity and blood glutathione (GSH) level, and an increased urinary excretion of delta-aminolevulinic acid (ALA) and an increased malondialdehyde (MDA) level in erythrocytes of rats exposed to GaAs. Hepatic GSH levels decreased, whereas there was an increase in GSSG and MDA levels. The results suggest a role of oxidative stress in GaAs-induced haematological and hepatic damage. Administration of DMSA and MiADMSA produced effective recovery in most of the above variables. However, a greater effectiveness of the chelation treatment (i.e. removal of both gallium and arsenic from body organs) could be achieved by combined administration of succimer (DMSA) with oxalic acid since, after MiADMSA administration, a marked loss of essential metals (copper and zinc) is of concern.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aminolevulinic acid	Delta-aminolevulinic acid dehydratase	Protein	Humans	Yes	Inducer	Details