84 THE DISTRIBUTION OF ENZYME ACTIVITIES IN CIRRHOTIC LIVERS OF DEVELOPING RATS SUGGESTS A SIMILAR METABOLIC ROLE FOR THE PERIPHERY OF THE RECENERATING NODULES & ZONE 3 OF THE NORMAL LIVER ACINUS

Abstract

To assess whether the development of experimental cirrhosis was associated with changes in the intralobular distribution of enzyme activities, we have used microspectrophotometry to quantitate in periportal (PPA) and centrilobular areas (CLA) of the liver succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), acid phosphatase (AP), glucose-6 phosphatase (GP) and NADPH diaphorase (ND). Rats were treated with phenobarbitone (PB) 30mg/kg/day from day 4 and CCl4 0.5mg/kg twice weekly from day 8 to 62 and developed centrilobular necrosis followed by fibrous tissue deposition from day 25 and cirrhosis by 45 days. During drug exposure, all enzymes showed decreased activity, particularly in the CLA, with SDH and GP falling by 85-90%, AP and GDH by 30-50% and ND by 10%. in the PPA, AP and ND showed little change, SDH and GDH decreased by 10-30% and GP by 40%. Although cirrhosis persisted after both drugs were stopped and enzymatic activity returned to normal, the distribution had changed, with the cells adjacent to the vascular fibrous septa at the periphery of the regenerating nodules expressing activities similar to the cells in the CLA of the controls, while enzyme activity in the centre of the nodules were similar to the PPA of the controls. Further application of this technique may elucidate metabolic and pharmacological complications of both experimental and clinical cirrhosis.