Dehydrogenase systems of different rat tissues in experimental alcoholism simulated by inhalation or forced intake of ethanol

Abstract

It is shown that alcoholization of rats during 1.5 months by the inhalation of ethanol vapors with a long-term subsidence into narcotic sleep results in alcohol dependence and marked shifts in the ratio between the activity of malate and lactate dehydrogenases and a change in the isoenzyme spectrum of the latter. This leads to an enhancement of aerobic processes in the brain and skeletal muscle tissues and of anaerobic processes in the liver and myocardium. Semiforced alcoholization of rats during 11 months, with ethanol solution serving as the only source of liquid, moderately lowers the ethanol tolerance and does not affect the dehydrogenase activity in the tissues examined. The effects of ethanol on the activity of functionally associated enzyme systems of malate and lactate dehydrogenases are believed to depend on the method of alcoholization and the type of tissue. Key Words: dehydrogenases; ethanol; simulation of alcoholism; carbohydrate metabolismThe most widespread model of alcoholism is based on semiforced alcoholization of animals [2,5,6]. This is a method whereby animals are given a 7.5-15% ethanol solution as a only source of liquid. Under such experimental conditions the narcotizing effect of ethanol is not obtained, since the animals themselves regulate the frequency of alcohol intake. The mean diurnal dose of alcohol (8-10 g/kg) slightly surpasses the basal level of ethanol metabolism in rats (7.2 g/2<gxday) [5]. Semiforced alcoholization under conditions of free choice results in a pronounced increase of the tolerance of alcohol and of its voluntary intake in just 30-40% of alcoholized rats.In the present study we explored the functional state of the dehydrogenase systems basing ourselves on the notion that systematic intake of high doses of ethanol markedly increases the NADH level in the tissues [3]. We used inhalation of ethanol vapors as an experimental model of alcoholism. The development of alcohol dependence was assessed as a change in the tolerance of ethanol, the level of motivation, and the activity of the enzymes malate dehydrogenase (MDH; EC 1.1.1.37) and lactate dehydrogenase (LDH, EC 1.1.1.27) in different tissues. In addition, the ratio between the activity of MDH and LDH (MDH:LDH) reflects the ratio between the aerobic and anaerobic oxidation of glucose and, therefore, the state of energy metabolism in the tissues [3].