s-1743 and Necrosis

After an accepted technique of abdominoplasty, a 66-year-old woman developed Clostridium difficile-associated diarrhea, leading to toxic megacolon and subsequent subtotal colectomy. The presumed etiology is chronic use of a proton pump inhibitor. This was addressed in a 2012 "white paper" warning issued by the Food and Drug Administration. This article presents the course of this case as well as a review of the pertinent literature.

Topics: Abdominoplasty; Aged; Colectomy; Enterocolitis, Pseudomembranous; Esomeprazole; Female; Humans; Intestinal Mucosa; Megacolon, Toxic; Necrosis; Proton Pump Inhibitors

Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 micromol/kg; indomethacin 100 micromol/kg; and esomeprazole 10, 30, or 60 micromol/kg plus indomethacin 100 micromol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10-60 micromol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Electron Transport Complex I; Electron Transport Complex II; Esomeprazole; Gastric Mucosa; Glutathione; Glutathione Disulfide; Indomethacin; Intubation, Gastrointestinal; Male; Membrane Transport Proteins; Mitochondria; Necrosis; Oxidative Phosphorylation; Rats; Rats, Wistar; Spectrophotometry; Stomach Diseases