Ranitidine as an inhibitor of liver regeneration

Abstract

The effects of ranitidine, a new H2-receptor antagonist, on liver regeneration were investigated using a protocol described previously. The animals in Group I had standard two-thirds hepatectomy. In Group II, the rats received an 8 mg/kg intramuscular dose of ranitidine immediately and 24 and 48 hours after two-thirds hepatectomy. In Group III, the rats had the same amounts of ranitidine after a sham operation. Mortality rate, liver weight restoration, mitotic activities of the residual livers, and serum levels of aminotransferases were examined from 24 hours to 14 days after operation. The mortality was very high in Group II (45 percent), whereas no rats died in Group I, and only 1 of 35 animals died in Group III. Administration of ranitidine after hepatectomy resulted in suppression not only of liver restoration, but also of the mitotic activities of hepatocytes. The serum aminotransferase levels in Group II had a tendency to increase after hepatectomy, compared with the levels in Group I. Using light microscopy, we detected that the hepatectomized group treated with ranitidine (Group II) underwent profound liver steatosis and marked dilatation of sinusoidal spaces. The present and previous observations by us indicate that ranitidine also inhibits, like cimetidine, liver regeneration after hepatectomy. The causes of the inhibitory effects of both cimetidine and ranitidine on hepatocyte cell division have also been discussed herein.