Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats

Abstract

Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood delta-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration of a higher dose of taurine (100 mg/kg) and MiADMSA provided more pronounced effects in improving the antioxidant status of liver and kidney and reducing body arsenic burden compared to the individual treatment of MiADMSA or taurine. The results suggest that in order to achieve better effects of chelation therapy, co-administration of taurine with MiADMSA might be preferred.

Keywords: arsenic toxicity; chelation; oxidative stress; taurine.

Figure 1

Chemical structure of taurine and MiADMSA.

Figure 2

Effects of MiADMSA and taurine co-administration on some biochemical variables suggestive of renal oxidative stress in arsenic exposed rats. Figure shows oxidative stress condition by the depletion of GSH level and elevation of GSSG level and significant recovery by co-administration of higher dose of taurine (100 mg/kg) and MiADMSA. GSH, reduced glutathione; GSSG, oxidized glutathione. Values are mean ± SE; n = 5. *,†,‡Means with matching symbol notations in each column are not significant at 5% level of significance

Figure 3

Effects of MiADMSA and taurine co-administration on arsenic concentration in blood and soft tissues. Figure shows significantly elevated level of arsenic in arsenic exposed animals which depleted more favorably during combined administration of taurine (100 mg/kg) and MiADMSA. MiA, monoisoamyl dimercaptosuccinic acid; As, arsenic. Values are mean ± SE; n = 5. *,†,‡,§Means with matching symbol notations in each column are not significant at 5% level of significance.