Mechanism for lowering blood ammonia levels by lactitol.
Lactitol has 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 ammonium 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.
Watanabe
M
M
Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Ozaki
T
T
Hirata
Y
Y
Yamamoto
O
O
Niida
H
H
Ueda
F
F
Yoshikuni
Y
Y
Kimura
K
K
D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity; D000284:Administration, Oral; D000641:Ammonia / Q000097:blood*; D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D002606:Charcoal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects; D004195:Disease Models, Animal; D005772:Gastrointestinal Transit / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects; D007792:Lactulose / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000008:administration & dosage / Q000494:pharmacology*
D000085:Acetates; D013402:Sugar Alcohols; D002606:Charcoal; D007792:Lactulose; D000641:Ammonia; C014635:lactitol; C018824:ammonium acetate