Cerebral metabolic and circulatory effects of 1,1,1-trichloroethane, a neurotoxic industrial solvent. 2. Tissue concentrations of labile phosphates, glycolytic metabolites, citric acid cycle intermediates, amino acids, and cyclic nucleotides.
In order to obtain information on the mechanisms of neurotoxicity of 1,1,1-trichloroethane, rats maintained artificially ventilated on N2O:O2 (70:30) were exposed to a concentration of 1,1,1-trichloroethane of 8000 ppm, 43.7 mg L-1, that induces moderate ataxia in awake, spontaneously breathing animals. After 5 and 60 min of exposure, as well as after a 60-min recovery period following 60 min of exposure, the brain was frozen in situ and cortical tissue was assayed for phosphocreatine (PCr), + ATP, ADP, AMP, glycogen, glucose, pyruvate, lactate, citric acid cycle intermediates, associated amino acids, and cyclic nucleotides; in addition, purine nucleotides, nucleosides, and bases were assayed by HPLC techniques. Exposure of animals to 1,1,1-trichloroethane failed to alter blood glucose, lactate, and pyruvate concentrations. However, the solvent induced highly significant increases in tissue lactate and pyruvate concentrations that were also reflected in cisternal CSF. Associated with these changes were increases in all citric acid cycle intermediates except succinate, an increase in alanine concentration, and a rise in the glutamate/aspartate ratio. After 5 min, a small decrease in glycogen concentration also occurred. All these changes were reversed when the exposure was terminated. No changes were observed in tissue concentrations of purine nucleotides, nucleosides, and bases except for a small reduction of ATP concentration after 60 min of exposure, still noticeable after 60 min of recovery. Apart from a small reduction in cAMP concentration after 5 min of exposure, cyclic nucleotide concentrations did not change.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D009705:Nucleosides / Q000378:metabolism; D009994:Osmolar Concentration; D010710:Phosphates / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents / Q000494:pharmacology; D014240:Trichloroethanes / Q000494:pharmacology*
D002951:Citrates; D006843:Hydrocarbons, Chlorinated; D007773:Lactates; D009498:Neurotoxins; D009705:Nucleosides; D010710:Phosphates; D011685:Purine Nucleotides; D011773:Pyruvates; D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D019343:Citric Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose