Inhibition of delta-aminolevulinic acid dehydratase by trichloroethylene.
Male Wistar rats (8 animals/group; 180-200 g) were exposed continuously to trichloroethylene (TRI) for 48 or 240 h or methylchloroform (1,1, 1-trichloroethane: MC for 48 h at 50, 400 and 800 ppm. The inhibition of delta-aminolevulinic acid dehydratase (ALA-D) was examined in liver, blood and bone marrow of naive and phenobarbital pretreated animals exposed to TRI. A clear cut dose-effect relationship between the exposure concentration or duration of exposure and the inhibition of ALA-D activity was seen for rats exposed to TRI. In addition to this finding, significant interaction between TRI exposure and phenobarbital treatment was observed in the inhibition of ALA-D in liver and blood. MC did not produce inhibition. Trichloroacetic acid and trichloroethanol failed to inhibit the ALA-D activity in vitro. It seems that a metabolite(s) of TRI other than the above 2 substances may play a role in the inhibition of ALA-D. The inhibition of ALA-D (38% or 48% of the control in liver or in blood, respectively) observed after the 240 h exposure at 400 ppm to TRI was accompanied by the significant elevation of delta-aminolevulinic acid synthase (186% of the control) in liver and the increase in excretion of delta-aminolevulinic acid in urine (142% of the control). This occurred without an apparent weight loss, liver injury or hematological changes.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D014238:Trichloroacetic Acid / Q000494:pharmacology; D014240:Trichloroethanes / Q000494:pharmacology; D014241:Trichloroethylene / Q000494:pharmacology*
D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; D000624:5-Aminolevulinate Synthetase; D000623:Porphobilinogen Synthase; D010634:Phenobarbital