deoxycholic-acid and Irritable-Bowel-Syndrome

Pyruvate is a normal constituent of the body that participates in carbohydrate metabolism and functions as a scavenger of free radicals. Calcium pyruvate monohydrate (CPM) is a more stable derivative that has proved its anti-inflammatory effect in experimental colitis, among other disorders, and that could also be considered a source of calcium. Thus, it would be useful for the treatment of diseases with an inflammatory component and a high prevalence of osteoporosis like the irritable bowel syndrome (IBS). The aim of the present study is to evaluate the effects of CPM in a rat model of chronic post-inflammatory visceral pain induced by deoxycholic acid (DCA) that resembles IBS. Rats were administered DCA for three days intracolonically and then treated daily with CPM (40 and 100 mg/kg) or gabapentin (70 mg/kg) (positive control) by oral gavage for 17 days. The treatments reduced the visceral hypersensitivity measured by response to colorectal distension and referred pain. DCA induced changes in the colonic immune response characterized by increased expression of the cytokine

Topics: Animals; Calcium; Calcium Compounds; Colitis; Colon; Cyclooxygenase 2; Deoxycholic Acid; Disease Models, Animal; Inflammation; Inflammation Mediators; Interleukin-1beta; Intestinal Mucosa; Irritable Bowel Syndrome; Male; Mucin-2; Mucin-3; Pain; Pain Threshold; Pyruvates; Rats, Sprague-Dawley; Toll-Like Receptor 3

Topics: Adenosine Monophosphate; Aminopyridines; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Anticoagulants; Antiemetics; Benzodioxoles; Cholagogues and Choleretics; Cystic Fibrosis Transmembrane Conductance Regulator; Deoxycholic Acid; Diarrhea; Drug Approval; Imidazoles; Irritable Bowel Syndrome; Spiro Compounds

About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion.. To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam.. A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4.. Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat.. Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

Topics: Adult; Allylamine; Bile Acids and Salts; Cholestenones; Colesevelam Hydrochloride; Deoxycholic Acid; Diarrhea; Feces; Female; Gastrointestinal Agents; Humans; Irritable Bowel Syndrome; Middle Aged