Effect of 5-aminosalicylic acid (5-ASA) and other salicylates on short-chain fat metabolism in the colonic mucosa. Pharmacological implications for ulcerative colitis.
5-Aminosalicylic acid (5-ASA) suppressed nitrite-stimulated oxidation of the fatty acid n-butyrate in a dose-dependent manner in isolated human and rat colonic epithelial cells. 4-ASA had one-sixth of the capacity of 5-ASA and sulphapyridine (SP) little of the capacity of 5-ASA to suppress fatty acid oxidation in human colonic epithelial cells. Sulphasalazine (SASP), azodisalicylic acid (ADS), acetyl-5-ASA and acetyl salicylic acid (ASA) did not suppress fatty acid oxidation in rat colonocytes. The suppression index of fatty acid oxidation (SIFO) of respective salicylic acids correlated with the reported clinical effectiveness of each drug against ulcerative colitis (UC). The capacity of 5-ASA to affect nitrite-stimulated oxidation of fat in the colonic mucosa suggests that nitrite ions and control of fatty acid oxidation play a central role in the development and therapy of active UC.
Roediger
W
W
Schapel
G
G
Lawson
M
M
Radcliffe
B
B
Nance
S
S
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D019804:Mesalamine; D009573:Nitrites / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D012459:Salicylates / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology
D000636:Aminosalicylic Acids; D005227:Fatty Acids; D009573:Nitrites; D012459:Salicylates; D012460:Sulfasalazine; D019804:Mesalamine; D013427:Sulfapyridine