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 μl of CC1₄ (LD₁₅) by gastric tube 36 h earlier, were isolated and perfused in a once-through system at 9 ml/min with a semi-synthetic 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 μmol/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 μmol × mirr⁻¹ × 100 g⁻¹ body weight (mean±SEM, P<0.001). The affinity constant was decreased from 0.18±0.06 to 0.11±0.02 mmol/l (mean±SEM, P<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.

Key Words:

• animals
• galactose
• kinetics
• liver function tests
• toxins