Impaired Detoxication of Hydrogen Sulfide in Ulcerative Colitis?

Abstract

Impaired butyrate oxidation and raised counts of sulfate-reducing bacteria in the colon of patients with ulcerative colitis (UC) indicate that the disease may be induced or aggravated by hydrogen sulfide toxicity. We aimed to examine enzymatic removal of H(2)S in erythrocytes and colonic mucosa from controls and patients with UC and Crohn's disease (CD). Rhodanese (RHOD) and thiol methyltransferase (TMT) activities were measured in rectal mucosa and erythrocytes, and plasma thiocyanate was determined. Four groups were analyzed: patients with UC, patients with CD, hospital controls (patients with dyspepsia or IBS), and a group of healthy volunteers. RHOD and TMT activity in rectal biopsies did not differ significantly between controls and patients with UC or CD (n=56). Control levels of RHOD were significantly higher in men than in women (212+/-25 and 132+/-14 nmol/mg/min, respectively; P<0.01). In erythrocytes (n=128) RHOD activity was significantly higher in UC patients than in hospital or volunteer controls (1.15+/-0.12 compared with 0.88+/-0.12 and 0.66+/-0.02 nmol/mg/min; P<0.05 and P<0.02, respectively). TMT activity was also significantly higher in erythrocytes from UC patients and hospital controls than volunteer controls (2.02+/-0.13 pmol/mg/min [P<0.001], 1.51+/-0.21 pmol/mg/min [P<0.05], and 1.17+/-0.18 pmol/mg/min, respectively). We found no evidence of defective enzymic detoxication of sulfide by RHOD or TMT in patients with UC or CD.

Hydrogen Sulfide: An Endogenous Mediator of Resolution of Inflammation and Injury

“…Largely based on these data, and observations of adverse effects of such concentrations of H 2 S on colonocyte function (5), roles for H 2 S in the pathogenesis of inflammatory bowel disease and colon cancer were suggested (4,45,46). However, this hypothesis has been challenged (25,26,38,42), as has the notion that there are millimolar concentrations of free H 2 S in the lumen of the gut (27,28,38,42,43). Most of the H 2 S that is produced in the lumen of the intestine is bound to fecal material and therefore not available to diffuse through the epithelium.…”

“…The H 2 S that is available, likely in micromolar concentrations, is absorbed and rapidly metabolized (51). Indeed, efficient detoxification occurs via a number of enzymes present in the mucosa, and no impairment of these detoxification systems has been detected in patients with ulcerative colitis or Crohn's disease (42). Based on studies utilizing a rat model of colitis (dextran sodium sulfate), Furne et al (21) concluded that ''excessive H 2 S production'' did not contribute to tissue injury.…”

Emerging role of hydrogen sulfide in colonic physiology and pathophysiology

“…42 Another study showed no difference in RHOD and TMT activity between controls and patients with UC. 43 As SRB are present in the colon and produce H 2 S, they have been implicated in the pathogenesis of UC. 19,44 SRB use sulfate as a terminal electron acceptor in metabolism, reducing it to sulfide.…”

Endogenous Production of H2S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

“…Cyanide is transferred to thiosulfate to create thiocyanate and sulfite. Picton and colleagues (52) used cyanide in colonic mucosal preparations, showed that thiocyanate is the major product of H 2 S degradation, and used this reaction as a surrogate for measuring H 2 S consumption to suggest that detoxification is impaired during colitis (52). After reexamination of their data, it appears that TST is involved in H 2 S oxidation only when cyanide is present (72) but is likely involved in formation of thiosulfate from oxidized sulfane persulfides (21).…”