title: Hydrogen sulfide and colonic epithelial metabolism: implications for ulcerative colitis.
abstract: Hydrogen sulfide (HS-) impairs the oxidation of butyrate in colonocytes and is found in excess in feces of patients with ulcerative colitis. The possible pathogenic role of HS- in ulcerative colitis was further investigated. To investigate the metabolic effect of free and bound fecal HS-, isolated rat colonocytes were incubated in the presence of butyrate without and with the addition of (1) HS- in water, (2) sterile filtrates of fecal homogenates supplemented and incubated with HS- and known sources of fecal HS- production, and (3) HS- incubated with fecal agents known to bind HS-. Oxidation rates were obtained by quantifying the production of CO2. Total and free HS-, as well as the fecal ability to bind HS-, were determined in health and ulcerative colitis. Compared to the production of CO2 by colonocytes incubated with 2 mmol/liter of butyrate, the further addition of 1.25 and 2.5 mmol/liter of HS- in water reduced the production of CO2 by 57.6+/-10.0 and 98.9+/-1.4%, respectively. However, when adding fecal filtrate of homogenate supplemented with HS- corresponding to 1.25 and 2.5 mmol/liter of HS- in water, the reduction of CO2 production was only 30.7+/-12.0 and 53.2+/-14.0%, respectively. Neither the fecal level of total or free HS- nor the remarkable fecal ability to bind HS- differed in health or quiescent and active ulcerative colitis. Bound HS- had no or little effect on CO2 production. Addition of fecal filtrate of nonsupplemented homogenate to colonocytes significantly reduced the oxidation of butyrate to CO2 about 25%, which could not be ascribed to fecal HS-. In conclusion, fecal HS- has little effect on butyrate oxidation in colonocytes and does not seem to play a pathogenic role for UC by impairing colonic epithelial metabolism. Other fecal agents seem to be more potent metabolic inhibitors than fecal HS-. The role of colonic contents in the pathogenesis of ulcerative colitis remains circumstantial.
authors.affiliation: Department of Medicine, Copenhagen University Hospital, The Rigshospital, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Jørgensen
authors.forename: P B
authors.initials: PB
authors.lastname: Mortensen
mesh_terms: D000328:Adult; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002087:Butyrates; D007657:Ketone Bodies; D002245:Carbon Dioxide; D006862:Hydrogen Sulfide