Serum Enzymes Derived from Liver Cell Fractions: I. The response to carbon tetrachloride intoxication in rats

This report tests the hypothesis that serum enzymes may reflect injury to the various subcellular organelles of liver cells, and serve as a biochemical biopsy which might be useful in differential diagnosis. The enzymes studied are found in liver cells but in different subcellular fractions: sorbitol dehydrogenase (cytoplasm), ornithine carbamyl transferase (mitochondria), microsomal liver esterase (endoplasmic reticulum), arylsulfatase-B (lysosomes), and nicotinamide mononucleotide adenylyl transferase (nuclei). As a model of acute hepatocellular injury, a single intragastric dose of CCl 4 (0.25 ml per 100 g) was given to rats and the temporal changes of these enzymes were measured in serum, subcellular fractions, and liver homogenate over a 96hr period. Serum sorbitol dehydrogenase activity increased by 3 hr and serum ornithine carbamyl transferase between 6 and 12 hr, times corresponding to the known onset of CCl 4 injury to cellular and mitochondrial membranes, respectively. Serum microsomal esterase did not increase until 23 hr after the onset of CCl 4 injury to the endoplasmic reticulum, however. The serum lysosomal and nuclear enzymes were normal throughout. No correlations were apparent between the serum activities of the first three enzymes and their specific activities in cell fractions or homogenates. Although the appearance in serum of an enzyme derived from a certain subcellular fraction is qualitative evidence of injury to the membrane system containing the enzyme, so many variables affect serum enzymes that the timing or degree of elevation does not predict the onset or severity of intracellular injury.