[Activity of catalase after administration of some ADH and MEOS inhibitors: in vitro investigation in rat liver homogenates].
In the first pass methanol biotransformation three enzymatic systems: alcohol dehydrogenase (ADH), microsomal alcohol oxidising system (MEOS) linked with cytochrome P-450 and catalase are involved. Because of the toxicity of methanol, which is directly caused by its toxic metabolites, the major task in clinical toxicology is to inhibit each of these enzymes to protect human life. The aim of this investigation was to check the influence of some effective inhibitors of ADH and MEOS: 4-methylpyrazole, cimetidine, EDTA and 1,10-phenantroline on the activity of catalase with methanol as a substrate and the comparison with 3-amino-1,2,4-triasole. Catalase activity in rat hepatic homogenates was measured spectrophotometrically in vitro at physiological pH 7.4 and temp. 37 degrees C, assaying the degree of methanol oxidation according to Handler and Thurman. The quantity of arising formaldehyde was measured according with the method of Nash. Our results have shown that catalase activity was inhibited to different extents by all investigated compounds at concentrations of 10(-3) mol/l, 2 x 10(-4) mol/l, 10(-4) mol/l, 2 x 10(-5) mol/l, 10(-5) mol/l. 1,10-Phenantroline was found to be a highly effective inhibitor in comparison with aminotriasole. 4-Methylpyrazole, EDTA, 1,10-phenantroline and aminotriasole are catalase competitive inhibitors and cimetidine is non-competitive inhibitor. 4-Methylpyrazole has shown higher affinity to the enzyme than aminotriasole.
Dawidek-Pietryka
Katarzyna
K
Katedra i Zakład Toksykologii Akademia Medyczna w Lublinie 20-093 Lublin, ul. Chodźki 8.
Dudka
Jarosław
J
Jagiełło-Wójtowicz
Ewa
E
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C092153:microsomal ethanol-oxidizing system; D000426:Alcohol Dehydrogenase; D002374:Catalase