The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine

Non-steroidal anti-inflammatory drugs are the most commonly prescribed drugs for arthritis, inflammation, and cardiovascular protection. However, they cause gastrointestinal complications. The pathophysiology of these complications has mostly been ascribed to non-steroidal anti-inflammatory drugs’ action on the cyclooxygenase inhibition and the subsequent prostaglandin deficiency. However, recent clinical demonstrated the prevalence of non-steroidal anti-inflammatory drugs-induced small intestinal mucosal injury is more often than previously expected. In this review, we discuss the defense mechanisms of stomach, and the pathophysiology of non-steroidal anti-inflammatory drugs-induced injury of stomach and small intestine, especially focused on non-steroidal anti-inflammatory drugs’ action on mitochondria

Lansoprazole inhibits mitochondrial superoxide production and cellular lipid peroxidation induced by indomethacin in RGM1 cells

Lansoprazole is effective in healing non-steroidal anti-inflammatory drugs induced ulcers, and antioxidant properties have been thought to play a key role in healing ulcers. We hypothesize that lansoprazole exerts a cytoprotective effect by inhibiting reactive oxygen species leakage from mitochondria and lipid peroxidation. We pretreated gastric epithelial RGM1 cells with lansoprazole and then treated them with indomethacin in vitro. We found that the lansoprazole pretreatment significantly reduced cellular injury, maintained mitochondrial transmembrane potential, and decreased lipid peroxidation. Furthermore, the signal intensity of the electron spin resonance spectrum of the indomethacin-treated mitochondria which were pretreated with lansoprazole showed considerable reduction compared to those without the lansoprazole pretreatment. These results suggest that lansoprazole reduced superoxide production in the mitochondria of indomethacin treated cells, and subsequently inhibited lipid peroxide and cellular injury in gastric epithelial cells