Inhibitory effect of cimetidine on liver regeneration after two-thirds hepatectomy in rats

The effects of cimetidine on the regenerating liver were studied in rats after they had two-thirds hepatectomy. In Group I, standard two-thirds hepatectomy was performed. In Group II, cimetidine in a dose of 40 mg/kg was given intramuscularly immediately and 24 and 48 hours after two-thirds hepatectomy. In Group III, the same amount of cimetidine was given after a sham operation. Mortality rate, liver weight restoration, mitotic activities of remnant livers, and serum levels of aminotransferases and albumin were examined from 24 hours to 14 days after operation. The mortality rate was 11.1 percent in Group II, whereas no rats in Groups I and III died. Although there were no differences in the residual liver weights among the hepatectomized groups, treatment with cimetidine induced substantial suppression and delay of liver cell division. The serum aminotransferase levels in Group II increased significantly after hepatectomy compared with the levels in Group I. The albumin synthesis remained suppressed in Group II. Light microscopy showed prolonged liver steatosis and marked dilatation of the sinusoidal space in that group. Our results may indicate that cimetidine has an inhibitory effect on liver regeneration and that it should be administered very carefully after extensive hepatic resection if applied as prophylaxis for the life-threatening complication, stress ulcer syndrome. Otherwise, antacid therapy or other trials should be carried out.