METHIONINE DERIVATIVES DIMINISH SULFIDE DAMAGE TO COLONOCYTES - IMPLICATIONS FOR ULCERATIVE-COLITIS

Background-Bacterial production of anionic sulphide is increased in th e 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 derivati ves. Methods and subjects-Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions (CO2)-C-1 4/acetoacetate generation was measured from [1-C-14]-butyrate (5.0 mmo l/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The eff ect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulp honate and DL-methionine-S-methylsulphonium chloride on sulphide inhib ited oxidation was observed. Results-In rat colonocytes sodium hydroge n sulphide dose dependently reduced oxidative metabolite formation fro m n-butyrate, an action reversed in order of efficacy by S-adenosylmet hionine 1,4 butane disulphonate>DLmethionine-S-methylsulphonium chlori de>L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved (CO2)-C-14 production (p=<0.0 05) suppressed by sodium hydrogen sulphide. Conclusion-Sulphide toxici ty in colonocytes is reversible by methyl donors. The efficiency of su lphide detoxification may be an important factor in the pathogenesis a nd treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value.