Arsenic antagonism studies with monoisoamyl DMSA and zinc in male mice

Abstract

Administration of zinc either alone or in combination with monoisoamyl dimercaptosuccinic acid (DMSA) during and post-arsenic exposure was investigated in male mice. The animals were administered 2 mg kg −1 arsenic as sodium arsenite, intraperitoneally, once daily for 5 days either alone or in combination with 10 mg kg −1, zinc (as zinc acetate, orally), 50 mg kg −1 monoisoamyl dimercaptosuccinic acid (MiADMSA) given orally (p.o.), 2 h after arsenic administration. Another group of arsenic treated animals was given both zinc (10 mg kg −1) and MiADMSA (50 mg kg −1, p.o.). Animals were sacrificed 24 h after the last dose. In another set of experimentation, arsenic pre-exposed mice (2 mg kg −1, i.p. for 5 days) were treated with saline, zinc, MiADMSA or zinc plus MiADMSA for next 3 days and sacrificed thereafter. Exposure to arsenic led to a significant inhibition of blood δ-aminolevulinic acid dehydratase (ALAD), depletion of glutathione (GSH) level and marginal elevations of zinc protoporphyrin (ZPP). Arsenic exposure caused a significant decrease in hepatic and renal GSH level and an increase in liver oxidized glutathione (GSSG) and liver and kidney thiobarbituric acid reactive substance (TBARS) levels. Concomitant administration of zinc with arsenic provided significant protection to blood ALAD activity while, GSH and ZPP levels remained unaltered. Co-administration of MiADMSA with arsenic significantly prevented accumulation of arsenic in blood, liver and kidney while, zinc had no effect on tissue arsenic concentration. Combined administration of zinc and MiADMSA had no major additional beneficial effects over their individual effects. Interestingly, post-arsenic exposure treatment with MiADMSA provided significant recovery in blood ALAD activity while, zinc supplementation alone had no effect. The best results however, were obtained when MiADMSA was administered along-with zinc. Most of the biochemical variables indicative of hepatic oxidative stress responded favorably to MiADMSA treatment while, zinc administration had no effect. Administration of MiADMSA significantly depleted arsenic concentration from the soft tissues while, combined zinc and MiADMSA had no additional beneficial effect over the individual effect of MiADMSA. The results thus lead us to conclude that in order to achieve best effects of chelation therapy, co-administration of zinc with chelator might be preferred. However, detailed experimental studies with variable doses and after chronic arsenic exposure are required.