Effect of methyl bromide on regional brain glutathione, glutathione-S-Transferases, monoamines, and amino acids in F344 rats

Both metabolic and neurotransmitter changes have been implicated in the pathogenesis of monohalomethane neurotoxicity in rodents. This study in male and female F344 rats examined the effects of methyl bromide (MeBr) on regional brain glutathione-S-transferase (GST) activities and concentrations of glutathione (GSH), monoamines, and amino acid. Inhalation exposure to 150 ppm MeBr (6 hr/day X 5 days) yielded no histologic evidence of brain lesions but resulted in a number of biochemical changes. GSH depletion and GST inhibition were detected in the frontal cortex, caudate nucleus, hippocampus (examined for GSH only), brain stem, and cerebellum from animals of both sexes. Differences between sexes were detected for GSH depletion. Simultaneous treatment of rats with the inhibitor of monohalomethane toxicity, BW 755C (3-amino-1-[m-(trifluoromethyl) phenyl]-2-pyrazoline; 10 mg/kg bw ip, 1 hr pre- and 1 hr postexposure) completely protected against GST inhibition in all brain regions of both sexes. Partial protection by BW 755C against GSH depletion was observed in the cerebral cortex and in the cerebellum only. In males, MeBr exposure had no effect on the regional concentrations of the monoamines dopamine and serotonin and the amino acids glutamate, glutamine, taurine, and gamma-aminobutyric acid. Regional increases of brain aspartate and glycine levels were observed after exposure of males to MeBr but BW 755C had no effect on these changes induced by MeBr. Thus, of all the parameters studied, only GST, and in some brain areas GSH, correlated with inhibition of toxicity. It is concluded that, in contrast to the monoamines and the amino acids, GST and GSH are sensitive and potentially relevant indicators of MeBr neurotoxicity which could explain sex and regional differences in response to the monohalomethanes.