ARSENIC-INDUCED CHANGES IN CERTAIN NEUROTRANSMITTER LEVELS AND THEIR RECOVERIES FOLLOWING CHELATION IN RAT WHOLE-BRAIN

Arsenic as sodium arsenite (100 ppm in drinking water) was administere d to male rats for 16 weeks. Animals were then treated either with mes o-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-s ulfonate (DMPS), dimethyl DMSA (DmDMSA), or diisopropyl DMSA (DiPDMSA) twice daily (50 mg/kg) intraperitoneally for 5 days. After 5 days of rest period, the animals were again given a second course of chelation therapy. The animals were sacrificed subsequently for the determinati on of whole brain biogenic amines levels, acetylcholinesterase (AChE), monoamine oxidase (MAO) and delta-aminolevulinic acid dehydratase (AL AD) activities. A number of biochemical parameters and arsenic concent rations in some tissues were also determined. The results suggest a si gnificant increase in brain arsenic concentration accompanied by alter ations in neurotransmitters levels following As(III) exposure. Althoug h chelation treatment was effective in reducing As burden, the altered biochemical variables responded less favorably to chelation therapy. The DMSA-diesters, particularly DiPDMSA, produced a more pronounced in crease in brain arsenic burden, as well as alterations in a few neurot ransmitters. It can be concluded that the lipophilic character of As a ntidotes may lead to unfavorable results following intraperitoneal adm inistration. (C) 1997 Elsevier Science Ireland Ltd.