Effect of selected alcohol dehydrogenase inhibitors on the human heart lactate dehydrogenase activity--an in vitro study.
Metabolic acidosis complicates methanol, ethylene glycol and other alcohol intoxications. It is caused firstly by acid metabolites and secondly by the lactate elevation. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH; EC 1.1.1.1) inhibitors and substrates: 4-methylpyrazole (4-MP), cimetidine, EDTA, ethanol and methanol on lactate dehydrogenase (LDH; EC 1.1.1.27) activity. The activity of LDH was determined spectrophotometrically in in vitro human heart homogenates with the mentioned compounds at 0.01, 0.1, 1.0 mM concentrations of 4-MP, cimetidine, EDTA, and 12.5, 25.0, 50.0 mM of ethanol and methanol. The LDH activity was significantly inhibited by 0.1 mM (p<0.05) and 1.0 mM (p<0.01) 4-MP and 1.00 mM EDTA (p<0.05). Higher LDH activity vs. control was observed in the samples incubated with all studied ethanol and methanol concentrations but these differences were not statistically significant. Thus, 4-MP was found to be the most effective inhibitor of LDH of all compounds tested. Therefore, such effect of 4-MP seems to be an additional advantage in methanol and ethylene glycol intoxications.
Dudka
J
J
Department of Clinical Pathomorphology, Medical University of Lublin, Poland. ave123@wp.pl
Burdan
F
F
Madej
Barbara
B
Szumilo
Justyna
J
Tokarska
Edyta
E
Korobowicz
Agnieszka
A
Klepacz
R
R
Chyzyńska
Monika
M
Korobowicz
Elzbieta
E
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D002927:Cimetidine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D000432:Methanol / Q000494:pharmacology; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010879:Piperazines; D000431:Ethanol; C077079:4-methylpiperazine-2,6-dione; D002927:Cimetidine; D004492:Edetic Acid; D000426:Alcohol Dehydrogenase; D007770:L-Lactate Dehydrogenase; D000432:Methanol