SKELETAL-MUSCLE PROTEASE ACTIVITIES ARE UNALTERED IN CIRRHOTIC RATS BUT ALTERED IN RESPONSE TO ETHANOL AND ACETALDEHYDE IN-VITRO

This study was carried out in an attempt to differentiate between the contribution of liver impairment and direct actions of alcohol in myop athy of alcoholic liver disease. Using an animal model of cirrhosis we have previously shown that protein synthetic potential in muscle was not significantly altered. We therefore investigated the possibility t hat muscle degradation is increased. Cirrhosis was induced by carbon t etrachloride gavage in male rats receiving phenobarbitone in their dri nking water. Controls were given phenobarbitone alone. After 135 days the free, latent and total activities of the lysosomal enzymes catheps in B and cathepsin D in gastrocnemius muscle were unaffected by the in duction of experimental cirrhosis when expressed relative to tissue we t weight, protein or DNA. The non-lysosomal enzyme neutral protease wa s also measured in gastrocnemius muscle from control and cirrhotic rat s. There was no difference between the two groups in the free, latent or total activities. Addition of ethanol and acetaldehyde to the assay mixtures in some cases significantly altered the relative activities of the proteases in latent and free compartments of the cirrhotic tiss ues. In control tissues a different pattern of response emerged. It is concluded that in cirrhosis, at least in the carbon tetrachloride-ind uced rat model, there is no change of the activity of cathepsin B and D and the neutral protease activity in gastrocnemius. Small but signif icant effects of ethanol and its metabolite acetaldehyde on latent and free muscle protease activity were demonstrated.