Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal damage in rats

Abstract

A comparison was made of the effects of a nonsulfhydryl compound, vitamin U (methylmethioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine (Cys), with regard to the inducement of acute gastric mucosal damage in the presence and absence of N-ethylmaleimide (NEM), a sulfhydryl-blocking reagent. The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to 50% ethanol. The preinjection of NEM had no effect on cytoprotection of prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased surface mucin content but lessened that of deep mucin. NEM decreased surface mucin and increased deep mucin. It thus follows that sulfhydryl compounds accelerate the secretion of deep mucin and accumulate surface mucin. The cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds, and the increase in surface mucosal mucin may possibly be related to cytoprotection.

Intragastrically Administered Lysophosphatidic Acids Protect Against Gastric Ulcer in Rats Under Water-Immersion Restraint Stress

“…Orally administered PC before and after ethanol-or indomethacin-induced acute gastric injury, significantly reduced lesions in rat stomachs, contributing to the mucosal defense [31]. Other preceding studies on the gastric mucosa-protective effects of exogenous compounds present in the gastric lumen are those reporting that methylmethioninesulfonium chloride, formerly called vitamin U, was effective in preventing acute gastric mucosal damage due to administration of 59% ethanol to rats, possibly by increasing the surface mucin content [33]. Oral administration of methylmethioninesulfonium chloride with cimetidine prevented suppression of reduced mucin accumulation on rat gastric surface induced by the histamine H 2 receptor antagonist [34].…”

Accelerated Wound Healing by <i>S</i>-Methylmethionine Sulfonium: Evidence of Dermal Fibroblast Activation via the ERK1/2 Pathway

“…Therefore, the anti-ulcer properties of SMMS have been widely studied, especially in the treatment of a variety of peptic ulcers [1,2,11,12] . Accelerated healing of gastric mucosal damage and a cytoprotective effect of SMMS is reportedly caused by increased mucin secretion [3,13] . Anti-ulcer properties, anti-inflammatory action, reduction of blood lipid, anti-depressant action and a cytoprotective effect of SMMS all have been demonstrated [3,14,15] .…”

Physiological Significance of Lysophospholipids that Act on the Lumen Side of Mammalian Lower Digestive Tracts

“…27) The PA flows down to the stomach where it might be converted to LPA by PLA 1 or PLA 2 activity, because pancreatic PLA 2 significantly converted PA in a lipid extract from cabbage leaves to LPA, a wound-healing factor, when they were incubated in the lumen of isolated mouse stomach. 27) The authors suggested that the gastric mucosa protective effect is mediated not only by methylmethionine sulfonium chloride, formerly called vitamin U, 70) but also by LPA, which is known as a woundhealing factor in animal skin and intestinal mucosa. The two isoforms of PA-specific PLA 1 (mPA-PLA 1 α/LIPH and β/LIPI) characterized to date are extracellular in their catalytic properties.…”