ABSTRACT-Lactitolhas been reported to decrease the blood ammonia concentration in various experimental hyperammonemia models such as portacaval shunted rats. The mechanism responsible for this lowering of blood ammonia levels was investigated in rats. When lactitol was given orally twice a day for 7 days at doses of 3 and 10 g/kg/day and at half that daily dose on day 8, it significantly decreased the ammonia concentration of the portal blood by 27.3-43.2%, cecal ammonia contents by 49.2-57.6%, and the pH of the cecal contents from 6.52 to 5.92 -5.54, 4 hr after the final administration. Lactitol also inhibited increases in the portal ammonia concentration induced by the intracecal administration of ammonium acetate (300 mg/kg) 4 hr after the final administration. When lactitol was given orally at bolus doses of 1 and 3 g/kg simultaneously with a charcoal meal, lactitol significantly facilitated small intestinal transit by 12-13%. At a bolus dose of 3 g/kg, given 1 hr before the administration of a charcoal meal into the proximal colon, lactitol significantly facilitated colonic transit by 29.5%. These effects of lactitol were similar to those of lactulose. These findings suggest that lactitol decreases blood ammonia concentration by inhibiting both the production and the absorption of ammonia through reducing intestinal pH and shortening the residence time of intestinal contents in the intestinal tract.Keywords: Lactitol, Mechanism, Blood ammonia level, Intestinal transit Hepatic encephalopathy is a metabolic disorder in which symptoms of psychosis/neuropathy and consciousness disorder caused by acute or chronic hepatic failure are manifested. The mechanism underlying the development of hepatic encephalopathy is not known. Since hyperammonemia is frequently observed in the development of this disease, however, ammonia has been noted as an important factor (1-3).Lactitol has been shown to decrease blood ammonia levels in portacaval shunted (PCS) rats treated with carbontetrachloride or dimethylnitrosamine (4). In addition, lactitol inhibits the increase of ammonia content in the brain and coma after administration of ammonium acetate in PCS rats treated with carbontetrachloride or dimethylnitrosamine (4).In the present study, we investigated the mechanism whereby lactitol lowers blood ammonia levels in rats.
MATERIALS AND METHODS
AnimalsMale Sprague-Dawley rats, 5 -7 weeks of age, were purchased from Japan SLC and used at 6-8 weeks of age.The rats were fed F-2 chow (Funabashi Farm, Funabashi) and received tap water ad libitum. They were kept in a room that was ventilated more than 15 times/hr, at a temperature of 21-251C and humidity of 45 % -65 % .
DrugsLactitol monohydrate [(+)-4-0-~-D-galactopyranosyln-glucitol monohydrate; NS-4, Zyma, Nyon, Switzerland; regarded as lactitol only] (Fig. 1) is a white odorless crystalline or crystallic powder that has a sweet taste. Lactitol was given as a solution in distilled water. As a reference drug, lactulose (Fig. 1, lactulose syrup containing 60% lactulose; Nikken, Tok...