N. Tripathi et al., ARSENIC-INDUCED CHANGES IN CERTAIN NEUROTRANSMITTER LEVELS AND THEIR RECOVERIES FOLLOWING CHELATION IN RAT WHOLE-BRAIN, Toxicology letters, 92(3), 1997, pp. 201-208
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.