Critical and timely review of the concept of gastric cytoprotection.

Gastric cytoprotection is a concept or phenomenon, and not a single magic mechanism of action of unusual compounds. It refers to prevention of acute hemorrhagic erosions where the superficial epithelial cells are not directly protected but are rapidly replaced by restitution in microvascular injury in subepithelial capillaries is prevented or diminished and blood flow is maintained. This gastroprotection achieved by prostaglandins (PG), sulfhydryls (SH) and non-SH antioxidants is thus real but relative by target, mechanisms and in time. PG and SH are the only two chemical entities with both pharmacologic and biochemical relevance, i. e., endogenous concentrations of PG and SH derivatives may be measured biochemically and correlated with the degree of gastroprotection. Despite differences in the chemical mechanisms of action (e. g., SH unlike PG scavenge free radicals and may directly influence SH-sensitive receptors, enzymes and membrane permeability), the structural and functional targets for both groups of compounds are essentially the same: prevention or reduction of microvascular injury in subepithelial capillaries, maintenance of blood flow which allows the energy-requiring rapid epithelial restitution to repair the superficial epithelial defect. This reductionist, critical and mechanistic overview highlights the recent developments and the persisting problems in study design, definitions and interpretation of results as well as some critical questions related to the concept of gastric cytoprotection.