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

Abstract

Backgrounds - 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 > 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.