Pleiotropic Benefits of Proton Pump Inhibitors Beyond Gastric Acid Control

Description

Abstract (English)

Proton pump inhibitors are recommended for the treatment of peptic acid disorders like duodenal ulcer, gastric ulcer,
oesophageal reflux disorders. They are also used for NSAID induced and for ischemia reperfusion related gastrointestinal
injuries. In addition to the anti secretary effect, PPIs have been found to have antioxidant, anti inflammatory and
antidiabetic properties They are also used as an adjunct in the treatment and prevention of chemoresistant tumors. Their
anti inflammatory property is attributed to the inhibition of expression of adhesion molecules on the neutrophils,
monocytes and the endothelial cells. In addition, decreased release of pro inflammatory mediators and up regulation of
heme oxygenase –l also contribute to this action. Keap-1/Nrf-2 and MAP kinases have role to play in the upregulation of
enzyme heme oxygenase-1 by PPIs. Inhibition of oxidative burst by neutrophils and impaired neutrophil migration also
help in anti inflammatory actions of PPIs. Antioxidant effect of PPIs is attributed to the scavenging of reactive oxygen
species, replenishment of protective sulfhydryl molecule in the gastric mucosa and the induction of heme oxygenase-1.
Recently anti diabetic properties of PPIs have been highlighted. PPIs mediate glucose lowering effect by increased
gastrin levels, increased beta cell neogenesis and mass, increased insulin secretion. Inhibition of ghrelin, activation of
central CCK-B receptors and GLP-1 activation from intestinal L cells also contribute to this effect. The PPIs are used as
an adjunct treatment for malignancy and also to prevent chemoresistance. The mechanism responsible for this effect
of PPIs on the malignant cells is through inhibition of V-ATPases and change in physiological pH which makes them
succeptible for apoptosis and self digestion. This also results in to the increased drug retention in the alkaline pH of
malignant cells.