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 × 10 −6 , 10 −5 and 5 × 10 −5 m as well as ethanol at concentrations of 12.50, 25.00, 50.00 m m . The LDH activity was significantly increased by 10 −5 and 5 × 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 × 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. Copyright © 2005 John Wiley & Sons, Ltd.