Effect of aldehyde dehydrogenase and alcohol dehydrogenase inhibitors and ethanol on blood and liver ketone bodies in the rat.
The effects of the aldehyde dehydrogenase (ALDH) inhibitors: cyanamide (CY) and disulfiram (DS) and the alcohol dehydrogenase (ADH) inhibitor, pyrazole (PY) and the combination of these drugs with ethanol (ET, 3.5 g/kg, ip 6 h before decapitation) on the concentrations of rat blood and liver ketone bodies were studied. We found a 2-fold increase in acetone 12 h after PY, 4-fold elevation 30 h after DS and a 14-fold rise 12 h after CY administration. While DS and PY had no pronounced effects on the blood acetoacetate and 3-hydroxybutyrate concentrations, CY increased both of them 5.5 and 3.4-fold, respectively. After combined PY+CY, DS+ET and CY+ET injection, the effect became potentiated and the blood acetone levels rose more than 20-fold. The ET injection increased the concentrations of liver ketone bodies. The DS pretreatment did not change the acetoacetate and 3-hydroxybutyrate concentrations found after ET, but CY increased that of acetoacetate. Thus, the DS- and PY-induced acetonemia may be related to decreased acetone catabolism, whereas the CY effect--to increased formation of acetone from its metabolic precursor, acetoacetate. The ALDH inhibitors potentiated the ethanol-induced acetonemia probably by a combination of disturbances in ketone bodies production and acetone metabolism.
Pronko
P
P
Institute of Biochemistry, Academy of Sciences of Belarus, Grodno.
Zimatkin
S
S
Kuzmich
A
A
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000097:blood / Q000378:metabolism; D000096:Acetone / Q000097:blood / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003484:Cyanamide / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004221:Disulfiram / Q000008:administration & dosage / Q000633:toxicity; D004357:Drug Synergism; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D006885:Hydroxybutyrates / Q000097:blood / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007657:Ketone Bodies / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats
D000090:Acetoacetates; D001786:Blood Glucose; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D011720:Pyrazoles; D000096:Acetone; D000431:Ethanol; C031280:pyrazole; D003484:Cyanamide; C016635:acetoacetic acid; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram; D020155:3-Hydroxybutyric Acid