ABSTRACT
The treatment of methanol intoxication usually focuses on prevention of methanol conversion to its toxic metabolites due to administration of ethanol or 4-methylpyrasole (4-MP). Nevertheless there is a need for new measures treatment of methanol intoxication. For this reason the influence of some alcohol dehydrogenase inhibitors on the activity of microsomal alcohol oxidising system (MAOS) with methanol as a substrate was assayed. In the present study MAOS activity was measured spectrophotometrically in vitro at physiological pH 7.4 and 37 degrees C, assaying the degree of methanol oxidation. The quantity of arising formaldehyde was measured according with the method of Nash. The source of enzyme was hepatic slices. Our results have shown that MAOS activity was inhibited to different extents by: 4-MP, isovaleric amide, cimetidine, DMSO, EDTA, o-phenantroline, pyrasole and theophylline at concentrations of 0.01 mmol/l, 0.10 mmol/l 1.00 mmol/l. And methylene blue, acetyl-L-carnitine and penicillamine increase MAOS activity in the process of methanol oxidation. In summary, 4-MP which plays an important role as an antidote in methanol intoxication was not an effective MAOS inhibitor. EDTA was found to be a highly effective inhibitor at all investigated concentrations.
Subject(s)
Alcohol Dehydrogenase/antagonists & inhibitors , Alcohol Dehydrogenase/metabolism , Alcohol Oxidoreductases/metabolism , Cytochrome P-450 Enzyme System/metabolism , Enzyme Inhibitors/pharmacology , Liver/metabolism , Methanol/metabolism , Humans , In Vitro Techniques , SpectrophotometryABSTRACT
In the present study it was found that Ukrain inhibits the ethanol oxidation process catalyzed by human alcohol dehydrogenase (ADH). Ukrain at a concentration of 10(-6), 2.5 x 10(-6), and 5.0 x 10(-6) M decreased liver ADH activity in the presence ethanol (approximately 8.41%, 13.28%, 16.69%, respectively) as well as in the presence of methanol (approximately 13.29%, 19.07% and 42.20%, respectively).
Subject(s)
Alcohol Dehydrogenase/metabolism , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Liver/enzymology , Adult , Berberine Alkaloids , Ethanol/pharmacology , Humans , In Vitro Techniques , Liver/drug effects , Male , Methanol/pharmacology , NAD/metabolism , PhenanthridinesABSTRACT
The liver is the major organ responsible for methanol and ethylene glycol oxidation, and alcohol dehydrogenase (alcohol: NAD+ oxidoreductase, EC 1.1.1.1.) is the main enzyme involved. In the present study, alcohol dehydrogenase (ADH) activity was measured spectrophotometrically in vitro at physiological pH 7.4 and 37 degrees C using human enzyme hepatic fraction. The percentage of residual activity was calculated for four inhibitors at concentrations of 10(-3), 10(-4), and 10(-5) M (pyrazole, 4-methylpyrazole, cimetidine, theophylline) and methylene blue at concentrations 10(-4) and 10(-5) M. Our results have shown that the best inhibitor, cimetidine, decreased oxidation of 0.1 M and 0.05 M methanol to 24 and 29% respectively at a drug concentration of 1 mM. Reaction with 0.1 M ethylene glycol as the ADH substrate was blocked by the same substances and 4-methylpyrazole was found to be a highly effective inhibitor.