title: Co-administration of meso 2,3-dimercaptosuccinic acid monoesters reduces arsenic concentration and oxidative stress in gallium arsenide exposed rats.
abstract: 1. Gallium arsenide (GaAs), a semiconductor, exerts toxicity as a result of its constitutive moieties; that is, gallium and arsenic that becomes dissociated after exposure. The present study focuses on reducing arsenic concentration from the target organs using monoesters of meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination. 2. Animals were exposed to GaAs (0.0014 mol/kg, orally for 8 weeks) and then treated with monoisoamyl DMSA (MiADMSA), monocyclohexyl DMSA (MchDMSA) or monomethyl DMSA (MmDMSA) either individually (0.3 mmol/kg, orally) or in combination (0.15 mmol/kg each, orally) for five consecutive days. 3. GaAs exposure significantly inhibited blood δ-aminolevulinic acid dehydrogenase (ALAD), suggesting alterations in the heme synthesis pathway. Whereas a significant increase in blood, liver and kidney reactive oxygen species accompanied by an increase in lipid peroxidation points to the involvement of oxidative stress in GaAs toxicity. 4. GaAs also significantly disturbed glutathione metabolism. Hepatic and renal catalase activity decreased significantly, whereas hepatic and renal superoxide dismutase activity, as well as serum transaminases activity, showed marginal increase. Treatment with MiADMSA in combination with MchDMSA showed better therapeutic efficacy compared with other treatments in the aforementioned variables. 5. Co-administration of MiADMSA with MchDMSA provided better therapeutic effects, including reduction of arsenic burden, compared with all other treatments.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India. sjsflora@hotmail.com
authors.forename: Swaran J S
authors.initials: SJ
authors.lastname: Flora
authors.forename: Kapil
authors.initials: K
authors.lastname: Bhatt
authors.forename: Nidhi
authors.initials: N
authors.lastname: Dwivedi
authors.forename: Vidhu
authors.initials: V
authors.lastname: Pachauri
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Kushwah
mesh_terms: D000622:Aminolevulinic Acid / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D001151:Arsenic / Q000097:blood*; D020261:Arsenic Poisoning / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D001152:Arsenicals / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003300:Copper / Q000097:blood; D005708:Gallium / Q000097:blood / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D004113:Succimer / Q000031:analogs & derivatives / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000637:Transaminases / Q000097:blood / Q000378:metabolism; D015032:Zinc / Q000097:blood
chemical_list: C505449:2,3-dimercaptosuccinic acid monocyclohexyl ester; D001152:Arsenicals; D017382:Reactive Oxygen Species; C043055:gallium arsenide; D006418:Heme; D003300:Copper; D000622:Aminolevulinic Acid; C091888:monoisoamyl-2,3-dimercaptosuccinate; D005708:Gallium; D004113:Succimer; D002374:Catalase; D013482:Superoxide Dismutase; D000637:Transaminases; D005978:Glutathione; D015032:Zinc; D001151:Arsenic