Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis.
BACKGROUND
Mercaptides (sodium hydrogen sulfide and sodium methanethiol) and mercapto-fatty acid (sodium mercaptoacetate) are reducing agents that help to maintain anaerobic conditions in the colonic lumen. The metabolic effect of these agents on n-butyrate and glucose oxidation in human colonocytes is unknown.


METHODS
Isolated human colonocytes were prepared from 31 colectomy specimens, and generation of oxidative metabolites from [1-14C]n-butyrate and [6-14C]glucose was measured in the presence and absence of reducing agents. Injury to cells was judged by diminished production of metabolites.


RESULTS
The injurious action of mercaptides at all sites of the colon was of the order of sodium hydrogen sulfide > methanethiol > mercaptoacetate. Significant inhibition of n-butyrate (< 0.005) but not glucose oxidation was observed with sodium hydrogen sulfide in the ascending colon, splenic flexure, and rectosigmoid region. Hydrogen sulfide more significantly inhibited fatty acid oxidation in the rectosigmoid than in the ascending colon (P < 0.02).


CONCLUSIONS
Metabolic effects of sodium hydrogen sulfide on butyrate oxidation along the length of the colon closely mirror metabolic abnormalities observed in active ulcerative colitis, and the increased production of sulfide in ulcerative colitis suggests that the action of mercaptides may be involved in the genesis of ulcerative colitis.
Roediger
W E
WE
Cell Physiology Laboratory, University of Adelaide, South Australia.
Duncan
A
A
Kapaniris
O
O
Millard
S
S
D003093:Colitis, Ulcerative / Q000209:etiology* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000633:toxicity; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000633:toxicity; D013455:Sulfur / Q000633:toxicity*; D013864:Thioglycolates / Q000633:toxicity
D005227:Fatty Acids; D013438:Sulfhydryl Compounds; D013864:Thioglycolates; C005231:methylmercaptan; D013455:Sulfur; C017487:2-mercaptoacetate; D005947:Glucose; D006862:Hydrogen Sulfide