Effect of cycloheximide on increased aspartate aminotransferase in carbon tetrachloride hepatotoxicity.

The previously reported increases in liver and serum aspartate aminotransferase (ASAT) activities and liver protein content 24 hours after the administration of carbon tetrachloride (CCl4) were reduced by administering multiple doses of the protein synthesis inhibitor cycloheximide (CH). Liver ASAT and protein content were reduced to saline-injected control levels, and the serum ASAT increase was reduced by 45.0 percent in rats given CH. Although there are morphological features of severe hepatotoxicity in the cycloheximide-carbon tetrachloride-injected rats, cycloheximide does reduce the severity of these lesions and the regenerative response. These findings lend some support to the hypotheses that (1) the increase in liver ASAT activity and protein content after CCl4 is due to increased synthesis and (2) the increase in serum ASAT after CCl4 is most likely due to a combination of increased synthesis and leakage from necrotic and damaged cells.