Mobilisation of Cadmium by meso‐ and racemic‐2,3‐Dimercaptosuccinic Acid (DMSA) in Rats

Abstract

A higher efficiency of cadmium binding with racemic than with meso-2,3-dimercaptosuccinic acid (rac-DMSA; meso-DMSA) was found in an in vitro speciation model by Fang et al. (1996). This finding has not yet been tested in vivo. This paper presents results on mobilisation of cadmium by meso-and rac-DMSA in rats. Cadmium chloride was administered as the radioactive isotope 109 Cd intraperitoneally to all animals. One group was an untreated control and two groups were treated with meso-and rac-DMSA, respectively. Treatment with chelators was applied twice, immediately after 109 Cd and 24 hr afterwards intraperitoneally at the dose of 1 mmol/kg, each. Six days later radioactivity was measured in the liver and kidneys. Whole-body counting was carried out on days 1, 2, 3 and 6 of the experiment. At the end of the experiment, both treatments caused a decrease in 109 Cd whole-body retention with rac-DMSA being more efficient (decrease from 83% in control to 74% and 64% in groups treated with meso-and rac-DMSA, respectively). The same reduction of 109 Cd was obtained by both chelators in the liver (from 57% to about 47%). In the kidney only rac-DMSA produced significant reduction of 109 Cd (from 5.3% to 3.5%). In conclusion, these results show modest reduction of cadmium in the body by two isoforms of DMSA with rac-DMSA being slightly more efficient than meso-DMSA.The most effective chelating agent for the treatment of acute oral cadmium intoxication is meso-2,3-dimercaptosuccinic acid (meso-DMSA). It effectively prevents the absorption of cadmium from the gastrointestinal tract (Jones 1991). However, to mobilise cadmium from its aged intracellular deposits from internal organs, other effective chelators were found since meso-DMSA was in this case not effective. Under these conditions most of other efficient chelators are basically carbodithioate derivatives (Jones & Cherian 1990; Singh et al. 1996a). Different esters or amides of meso-DMSA were also studied for mobilisation of aged intracellular deposits of cadmium with varying success (Jones et al. 1988(Jones et al. , 1992(Jones et al. , 1994aSingh et al. 1996b). Recently the racemic isoform of DMSA (rac-DMSA) has been found to be more efficient than the meso-DMSA to mobilise other metals such as lead and mercury Kostial et al. 1997). Fang et al. (1996) have recently found higher efficiency of cadmium-binding with rac-than with meso-DMSA in an in vitro speciation model. To our knowledge rac-DMSA has not been tested in vivo to mobilise cadmium from the body and organs.In this study we compared the efficiencies of meso-and rac-DMSA to mobilise cadmium in vivo after intraperitoneal administration in rats. Materials and MethodsExperimental design. The experiment was conducted on 30 3.5 week-old female albino Wistar rats (average body-weight of 50 g) from the breeding farm of the Institute for Medical Research and Occupational Health (Zagreb, Croatia). The animals were kept in polycarbonate cages (9-11 in each) during the experiment. Food (Domžale, Slove...