Trimethyltin-induced alterations in brain amino acids, amines and amine metabolites: relationship to hyperammonemia

Neurotoxicology. 1986 Fall;7(3):63-74.

Abstract

An investigation of several neurochemical consequences of exposure of the rat to 3/4 of the estimated single injection LD50 quantity of trimethyltin chloride (TMT) indicated that a significant elevation in the levels of glutamine (Gln) and 5-hydroxyindole acetic acid (5-HIAA) occurred at post-dosing day 7 in each examined region of the brain; elevated Gln persisted in the hippocampus through day 14 and returned to control levels at day 28. At post-dosing day 7, levels of glutamate were decreased in the hippocampus, while levels of GABA were decreased in hippocampus and frontal cortex, but not in corpus striatum; hippocampal glutamate and GABA returned to control levels by post-dosing day 14. Decreased levels of taurine (Tau) occurred on day 7 in both hippocampus and frontal cortex; hippocampal Tau remained below control levels through post-dosing day 28. Levels of other amino acids and of amines and amine metabolites were not altered by TMT in the 7 to 28 day post-dosing interval. At day 7, TMT treatment did not alter brain regional activities of glutamine synthetase; however, plasma ammonia was elevated 100% above the control value. Alterations in several serum enzymes (esp., alkaline phosphatase and aspartate aminotransferase) revealed several other peripheral consequences of TMT exposure which persist through post-dosing day 28. The more prominent and wide-spread neurochemical alterations resulting from TMT exposure appear to reflect consequences of hyperammonemia resulting from a peripheral effect of the organotin compound.

MeSH terms

  • Amino Acids / metabolism*
  • Ammonia / blood*
  • Ammonia / metabolism
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Catecholamines / metabolism*
  • Cerebral Cortex / metabolism
  • Corpus Striatum / metabolism
  • Glutamate-Ammonia Ligase / metabolism
  • Glutamine / metabolism
  • Hippocampus / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Rats
  • Rats, Inbred F344
  • Serotonin / metabolism
  • Trialkyltin Compounds / toxicity*
  • Trimethyltin Compounds / toxicity*

Substances

  • Amino Acids
  • Catecholamines
  • Trialkyltin Compounds
  • Trimethyltin Compounds
  • Glutamine
  • trimethyltin
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Ammonia
  • Glutamate-Ammonia Ligase