Effects of acute carbon tetrachloride intoxication on kinetics of galactose elimination by perfused rat livers

Abstract

Seventeen livers of 200 g rats, of which seven had received 435 microliters of CCl4 (LD15) by gastric tube 36 h earlier, were isolated and perfused in a once-through system at 9 ml/min with a semi-śynthetic medium to which galactose was added to concentrations from 0.1 to 3.3 mmol/l. The relative liver weight was increased by 13% by CCl4. The portal pressure was 16 cmH2O and the oxygen consumption of the livers 20 mumol/min, both unchanged by CCl4. In each liver four to six sets of galactose elimination rate at different galactose concentrations were measured. The relation was examined by a model including modification of the simple Michaelis-Menten kinetics by allosterism. The resulting Vmax values were decreased by CCl4 from 1.20 +/- 0.18 in controls to 0.78 +/- 0.19 mumol X min-1 X 100 g-1 body weight (mean +/- SEM, P less than 0.001). The affinity constant was decreased from 0.18 +/- 0.06 to 0.11 +/- 0.02 mmol/l (mean +/- SEM, P less than 0.015) in CCl4-treated livers. The decrease in affinity constant may--if it also applies to other substances eliminated by the liver--have implications for the use of a clearance as a measure of functional capacity, since this presupposes that the affinity constant remains unchanged during liver disease.