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 administered to male rats for 16 weeks. Animals were then treated either with meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-sulfonate (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 determination of whole brain biogenic amines levels, acetylcholinesterase (AChE), monoamine oxidase (MAO) and delta-aminolevulinic acid dehydratase (ALAD) activities. A number of biochemical parameters and arsenic concentrations in some tissues were also determined. The results suggest a significant increase in brain arsenic concentration accompanied by alterations in neurotransmitters levels following As(III) exposure. Although 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 increase in brain arsenic burden, as well as alterations in a few neurotransmitters. It can be concluded that the lipophilic character of As antidotes may lead to unfavorable results following intraperitoneal administration.
Tripathi
N
N
Divison of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Kannan
G M
GM
Pant
B P
BP
Jaiswal
D K
DK
Malhotra
P R
PR
Flora
S J
SJ
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015306:Biogenic Monoamines / Q000032:analysis; D001923:Brain Chemistry / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000032:analysis*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D051381:Rats
D015306:Biogenic Monoamines; D002614:Chelating Agents; D018377:Neurotransmitter Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000623:Porphobilinogen Synthase; D001151:Arsenic