[Activity of the enzymes of ethanol and acetaldehyde metabolism in rats with varying initial sensitivity to alcohol]. / Aktivnost' fermentov metabolizma étanola i atsetal'degida u krys s razlichnoi iznachal'noi chuvstvitel'nost'iu k alkogoliu.

The experiments were carried out on male rats with different sensitivity to alcohol. To assess sensitivity to ethanol effects, we have used ethanol-induced sleep time and variations in rectal temperature of alcohol-intoxicated animals. Activity of alcohol dehydrogenase, microsomal ethanol-oxidizing system, catalase and aldehyde dehydrogenase in the liver as well as ethanol and acetaldehyde levels in the blood were determined after alcohol intoxication (3.5 g/kg, i.p., 8 days). The development of alcohol tolerance was accompanied by induction of the microsomal ethanol-oxidizing system in long-sleeping rats and in short-sleeping rats as well as by an increase in ethanol and acetaldehyde levels in the blood.

[Effect of pyruvate, threonine, and phosphoethanolamine on acetaldehyde metabolism in rats with toxic liver injury]. / Vliianie piruvata, treonina i fosfoétanolamina na obmen éndogennogo atsetal'degida u krys s toksicheskim porazheniem pecheni.

Pyruvate dehydrogenase, threonine aldolase and phosphoethanolamine lyase can produce acetaldehyde during normal metabolism. We studied the effect of loading with the substrates of these enzymes (pyruvate, 500 mg/kg, i.p., threonine 500 mg/kg, i.p., and phosphoethanolamine, 230 mg/kg, i.p.) on the blood concentrations of endogenous acetaldehyde and ethanol and the activities of enzymes producing and oxidizing acetaldehyde in the liver of normal rats and rats with liver injury provoked by chronic carbon tetrachloride (CCl4) treatment (0.2 ml i.p. per rat, 2 times a week during 4 weeks). Blood was collected before the treatment and then 30 min and 1 h following the administration of the substrates to intact and CCl4-treated rats. Endogenous acetaldehyde and ethanol were determined by headspace GC. The CCl4 treatment resulted in decreased liver alcohol dehydrogenase and aldehyde dehydrogenase activities and a significant elevation of liver endogenous ehtanol and a clear tendency to enhance blood acetaldehyde levels. Pyruvate increased blood endogenous acetaldehyde in CCl4-treated animals and endogenous ethanol--in the control group of animals. Threonine elevated endogenous acetaldehyde in normal rats. Phosphoethanolamine increased endogenous ethanol in the intact and CCl4 groups. At the same time, in CCl4-treated rats pyruvate administration increased the liver pyruvate dehydrogenase, threonine decreased threonine aldolase, whereas phosphoethanolamine decreased phosphoethanolamine lyase. Thus, the CCl4 effect on blood endogenous acetaldehyde and ethanol may be mediated through decreased liver ALDH and ADH activities. Liver injury promotes the accumulation of acetaldehyde, derived from physiological sources, including the degration of pyruvate and threonine by decreased acetaldehyde oxidation.

[Effect of acetaldehyde on ethanol- and aldehyde-metabolising systems of the liver and brain of rats]. / Vliianie atsetal'degida na étanol- i al'degidmetaboliziruiushchie sistemy pecheni i mozga krys.

Lately the mechanism of craving for alcohol has been related to the local level of brain acetaldehyde occurring in ethanol consumption and depending on the activities of the brain and liver ethanol and acetaldehyde-metabolizing systems. In this connection, we studied the effect of chronic acetaldehyde intoxication on the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), the microsomal ethanol oxidizing system (MEOS) and liver and brain catalase as well as ethanol and acetaldehyde levels in the blood. The results showed that the chronic acetaldehyde intoxication did not alter significantly the activities of liver ADH, MEOS and catalase as well as liver and brain ALDH. In parallel with this, the systemic acetaldehyde administration led to shortened time of ethanol narcosis and activation of catalase in the cerebellum and left hemisphere, which may indicate involvement of this enzyme into metabolic tolerance development.

[Effect of alcohol intoxication and aldehyde dehydrogenase inhibitors on lipid peroxidation in rat liver]. / Vliianie alkogol'noi intoksikatsii i ingibitorov al'degiddegidrogenazy na peroksidnoe okislenie lipidov v pecheni krys.

A single intraperitoneal administration of ethanol (3.5 g/kg) to rats induced a marked increase in lipid peroxidation and a decrease of antioxidative activity in the liver after 1 h when assessed by chemi-luminescence in liver homogenates. The pretreatment with aldehyde dehydrogenase inhibitor, disulfiram (200 mg/kg 24 hr before ethanol), caused a 10-fold elevation of the blood acetaldehyde levels, with no effect on the hepatic lipid peroxidation compared to control. Cyanamide (50 mg/kg, 2 h before the ethanol) increased approximately 100-fold the acetaldehyde levels, however, the changes in lipid peroxidation were not significantly different from that produced by ethanol alone. The present results suggest, that the metabolism of acetaldehyde and not acetaldehyde itself is responsible for the in vivo activation of lipid peroxidation during acute alcohol intoxication. Disulfiram prevents the ethanol-induced lipid peroxidation in the rat liver.

LPO and ethanol biotransformation systems in the liver as markers of predisposition to ethanol hepatotoxicity.

An original experimental model for detecting organ-specific markers of predisposition to ethanol hepatotoxicity is proposed. A relationship between congenital activity of LPO processes in rat liver (before ethanol intoxication) and the type and severity of ethanol-induced damage to the liver was demonstrated using methods of mathematical modeling. It was proven that intact rats with genetically high MDA levels in the liver and more active systems of MDA generation in ascorbate- and NADPH-dependent reactions are prone to ethanol-induced damage to the liver.