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 betweenthe contribution of liver impairment and direct actions of alcoholin myopathy of alcoholic liver disease. Using an animal modelof cirrhosis we have previously shown that protein syntheticpotential in muscle was not significantly altered. We thereforeinvestigated the possibility that muscle degradation is increased.Cirrhosis was induced by carbon tetrachloride gavage in malerats receiving phenobarbitone in their drinking water. Controlswere given phenobarbitone alone. After 135 days the free, latentand total activities of the lysosomal enzymes cathepsin B andcathepsin D in gastrocnemius muscle were unaffected by the inductionof experimental cirrhosis when expressed relative to tissuewet weight, protein or DNA. The non-lysosomal enzyme neutralprotease was also measured in gastrocnemius muscle from controland cirrhotic rats. There was no difference between the twogroups in the free, latent or total activities. Addition ofethanol and acetaldehyde to the assay mixtures in some casessignificantly altered the relative activities of the proteasesin latent and free compartments of the cirrhotic tissues. Incontrol tissues a different pattern of response emerged. Itis concluded that in cirrhosis, at least in the carbon tetrachloride-inducedrat model, there is no change of the activity of cathepsin Band D and the neutral protease activity in gastrocnemius. Smallbut significant effects of ethanol and its metabolite acetaldehydeon latent and free muscle protease activity were demonstrated.