Effect of selected alcohol dehydrogenase inhibitors on human hepatic lactate dehydrogenase activity - an in vitro study.
Metabolic acidosis severely complicates methanol and ethylene glycol intoxications. Acidosis is caused by acid metabolites and can be intensified by lactate elevation. Lactate concentration depends on the NADH(2)/NAD ratio. Lactate dehydrogenase (LDH, E.C.1.1.1.27.) supplies more lactate when the level of NADH(2) is elevated. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH) inhibitors and substrates: cimetidine, EDTA, 4-methylpyrazole (4-MP), Ukrain and ethanol on LDH activity. The activity of LDH was determined spectrophotometrically in human liver homogenates incubated with cimetidine, EDTA, 4-MP and Ukrain at concentrations of 2 x 10(-6), 10(-5) and 5 x 10(-5) m as well as ethanol at concentrations of 12.50, 25.00, 50.00 mm. The LDH activity was significantly increased by 10(-5) and 5 x 10(-5) m concentrations of cimetidine and 4-MP, and by all concentrations of ethanol. The most effective change of LDH activity of about 26% (P<0.01) was observed at the highest concentration of ethanol. Ukrain inhibited LDH activity at both concentrations, i.e. 10(-5) and 5 x 10(-5) m (P<0.05). However, EDTA did not significantly influence LDH activity. The data showed that ethanol and 4-MP, the main antidotes in methanol or ethylene glycol poisoning, may increase liver LDH activity - an undesirable effect during the therapy of patients intoxicated with these alcohols. On the other hand, the decrease of LDH activity in the presence of Ukrain is a promising finding but definitely requires further investigation.
Dudka
Jaroslaw
J
Department of Clinical Pathomorphology, Medical University of Lublin, PL-20-950 Lublin, Poland. ave123@wp.pl
Burdan
Franciszek
F
Szumilo
Justyna
J
Tokarska
Edyta
E
Korobowicz
Agnieszka
A
Klepacz
Robert
R
Gieroba
Renata
R
Madej
Barbara
B
Korobowicz
Elzbieta
E
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001600:Berberine Alkaloids / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D000077604:Fomepizole; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology
D001600:Berberine Alkaloids; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D011720:Pyrazoles; D000431:Ethanol; C060921:ukrain; D002927:Cimetidine; D000077604:Fomepizole; D004492:Edetic Acid; D000426:Alcohol Dehydrogenase; D007770:L-Lactate Dehydrogenase