Methionine derivatives diminish sulphide damage to colonocytes--implications for ulcerative colitis

Gut. 1996 Jul;39(1):77-81. doi: 10.1136/gut.39.1.77.

Abstract

Background: Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes.

Aims: To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives.

Methods and subjects: Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed.

Results: In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide.

Conclusion: Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / analysis
  • Animals
  • Butyrates / metabolism*
  • Butyric Acid
  • Carbon Dioxide / metabolism
  • Carbon Radioisotopes / metabolism
  • Cells, Cultured
  • Colitis, Ulcerative / metabolism
  • Colon / drug effects
  • Colon / metabolism*
  • Humans
  • Male
  • Methionine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • S-Adenosylmethionine / analogs & derivatives
  • S-Adenosylmethionine / pharmacology*
  • Scintillation Counting
  • Sulfides / pharmacology
  • Vitamin U / pharmacology*

Substances

  • Acetamides
  • Butyrates
  • Carbon Radioisotopes
  • Sulfides
  • Butyric Acid
  • Carbon Dioxide
  • Vitamin U
  • S-Adenosylmethionine
  • Methionine