Effect of lactitol (NS-4) on the increase in blood and brain ammonia concentration and on coma in newly developed rat models of hepatic coma

Abstract

Encephalopathy caused by hepatic cirrhosis is often associated with portasystemic shunt and hepatic parenchymal injury. Together, these are known as a combined-type symptom. Two experimental hepatic comatose models with combined-type symptom were developed in rats. Both of these models involve the administration of ammonium acetate (500 mg/kg) into the cecum in portacaval shunted (PCS) rats. In addition, hepatic injury was induced in one model by carbontetrachloride (CCl4) and in the other by dimethylnitrosamine (DMNA). These model rats showed a higher increase in the concentration of ammonia in the blood and a higher incidence of coma as determined by the loss of the righting reflex than did rats subjected to a shunt only (PCS operation + ammonia loading) or hepatic parenchymal injury only (CCl4 treatment + ammonia loading). The effect of lactitol, administered orally for 7.5 days, on the experimental hepatic coma was compared with that of lactulose. Lactitol significantly inhibited the increase in blood and brain ammonia concentration at doses of 3 and 6 g/kg/day and also reduced the incidence of coma. The effects of lactitol were similar to those of lactulose, a therapeutic agent for hepatic encephalopathy. Therefore, lactitol should be useful in the clinical treatment of hyperammonemia or hepatic encephalopathy.