Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion

seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. “adaptive cytoprotection”). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective,

that is, a key element in the complex pathophysiologic response during selleck chemicals acute gastroprotection. Over the years, “gastroprotection” was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth Tamoxifen price factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence “gastric cytoprotection” research is still relevant. It’s not widely known that gastroprotective drugs (e.g. sofalcone, sucralfate) which prevent and/or accelerate healing of gastric ulcers, without inhibiting acid secretion, were first introduced in Japan, before or around Andre Robert’s historic article on “gastric cytoprotection” in 1979.[1, 2] Furthermore,

some poorly defined and locally acting “protective” drugs (e.g. carbenoxolone and bismuth salts) were empirically used in Europe and North America, but their mechanisms of action were not widely investigated.[3] Since medchemexpress Robert’s studies were solely focused on prostaglandins (PG), they became the center of gastrointestinal (GI) research for more than 30 years, preceding the popularity of Helicobacter pylori investigations. As endogenous products, PG were implicated in mediating the gastroprotective effect of other drugs such as sofalcone and sucralfate[4, 5] despite that the cyclooxygenase inhibitor indomethacin diminished but never abolished gastroprotection by other drugs. Another group of endogenous substances, that is, sulfhydryls (SH), investigated in parallel with PG, also seem to play a mechanistic role in gastroprotection, especially since SH alkylators like N-ethylmaleimide (NEM) counteract virtually any form of gastroprotection.