Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucosa

Abstract

Famotidine-induced suppression of gastric surface mucus cell function is prevented by combined treatment with MMSC, raising the possibility of a more effective cure of PUD.

Different effects of two types of H2-receptor antagonists, famotidine and roxatidine, on the mucus barrier of rat gastric mucosa

“…Because treatment with an acid suppressant, such as H 2 -receptor antagonist or proton pump inhibitor, is highly effective for peptic ulcer disease, it may be difficult to estimate the additive or synergistic effects of combination therapy on ulcer healing. Recent work in rats documents that a certain mucosal protectant contributes to reducing the adverse effects of long-term treatment with famotidine (11,21), and the present study showed the suppression of gastric surface mucus cell function caused by administration of famotidine for 7 days. On the basis of these findings, it is important for more effective ulcer therapy to evaluate the function of surface mucus cells in gastric mucosal defense during long-term treatment with acid suppressant.…”

“…On the basis of the belief that ulcers occur as a result of an imbalance between aggressive and defensive factors, such as mucus secretion and mucosal blood flow, they are often treated in Japan with a combination of an acid suppressant (e.g. H 2 -receptor antagonist or proton-pump inhibitor) and a mucosal protectant (4,11,16,18,19,25).…”

“…There was no difference between the groups in the content and immunoreactivity of mucous neck cell-derived mucin. H 2 -receptor antagonists should be classified in relation to gastric surface mucus cell function, raising the possibility of more effective ulcer therapy.While acid, pepsin, and Helicobacter pylori are thought to be major factors in the pathophysiology of peptic ulcer diseases, the importance of the mucosal defense system has also been emphasized (4,11,16,18,19,25). On the basis of the belief that ulcers occur as a result of an imbalance between aggressive and defensive factors, such as mucus secretion and mucosal blood flow, they are often treated in Japan with a combination of an acid suppressant (e.g.…”

“…On the basis of the belief that ulcers occur as a result of an imbalance between aggressive and defensive factors, such as mucus secretion and mucosal blood flow, they are often treated in Japan with a combination of an acid suppressant (e.g. H 2 -receptor antagonist or proton-pump inhibitor) and a mucosal protectant (4,11,16,18,19,25).Recent prospective randomized trials indicated that the addition of a mucosal protectant significantly augmented gastric ulcer healing and symptom relief by cimetidine (18,19). Compared with the aggressive factors, little attention has been paid to the mucosal defensive factors in ulcer therapy, and the role of the H 2 -receptor antagonists in gastric mucosal protection has not been well characterized.…”

Protective Effects of Gastric Mucus

“…Of the four H 2 -blockers shown in Figure 10, lafutidine and roxatidine have a stimulant effect on mucin biosynthesis in the rat gastric mucosa. In contrast, first-generation H 2 -receptor antagonists such as cimetidine, ranitidine and famotidine, failed to stimulate mucin biosynthesis (Ichikawa et al, 1994b(Ichikawa et al, , 2009b. Second-generation H 2 -blockers, lafutidine and roxatidine, have been reported to prevent the formation of gastric mucosal lesions induced by necrotizing agents in rats (Fukushima et al, 2006;Shiratsuchi et al, 1988), and this effect may be due not only to the inhibition of aggressive factors such as acid, but also to the maintenance of defensive factors such as mucus.…”