ALTERATION OF ACETALDEHYDE METABOLISM IN CARBON TETRACHLORIDE-INTOXICATED RAT LIVER: ANALYSIS USING LIVER PERFUSION SYSTEM

Abstract

The heptic metabolism of acetaldehyde in carbon tetrachloride (CCl4)-intoxicated rats was studied using a non-recirculating haemoglobin-free liver-perfusion system. Acetaldehyde uptake by the liver from acutely CCl4-treated animals (4.16 mmol/kg,i.p.) at 24 hr after the treatment was not significantly altered, whereas that by the liver from chronically CCl4-treated animals (2.08 mmol/kg,i.p., twice a week, for 8-12 weeks) was decreased by approximately 50% when it was determined in the presence of 0.01-5 mM acetaldehyde. In liver from rats chronically intoxicated with CCl4, the following important biochemical changes were observed: (1) The activity of low Km aldehyde dehydrogenase (ALDH) in hepatic mitochondria was decreased by approximately 75%. (2) The basal levels of the lactate/pyruvate (cytosolic [NADH]/[NAD+]) ratio as well as the beta-hydroxybutyrate/acetoacetate (mitochondrial [NADH]/[NAD+]) ratio were elevated by more than 2-fold. (3) Mitochondrial NADH oxidation was also reduced by approximately 35% of the control level. (4) The basal level of hepatic oxygen uptake was attenuated by approximately 50%, and the infusion of acetaldehyde (0.01-5.0 mM) caused a further decrease in the uptake. (5) The rate of ethanol production from acetaldehyde by the catalytic action of alcohol dehydrogenase was found to be unaltered when low concentrations of acetaldehyde (0.01-0.2 mM) were used, whereas a significant suppression of the rate of ethanol production was detected in the presence of high concentrations of acetaldehyde (0.6-5 mM).(ABSTRACT TRUNCATED AT 250 WORDS)