title: NSAIDs and acidic environment induce gastric mucosal cellular mitochondrial dysfunction.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal complications such as gastric ulcers and erosions. Recent studies on the pathogenesis have revealed that NSAIDs induce lipid peroxidation in gastric epithelial cells by generating superoxide in mitochondria, independently with cyclooxygenase inhibition and the subsequent prostaglandin deficiency. More recently, gastric hydrochloric acid (HCl) has been regarded as an inciting factor of gastric mucosal injuries, and reportedly induced cellular lipid peroxidation in vitro. We hypothesized that gastric acid and NSAID treatment synergistically induce cellular injury in gastric epithelial cells. We treated gastric epithelial RGM1 cells with acidic solutions and NSAIDs, and examined cellular injury, lipid peroxidation, mitochondrial transmenbrane potential and mitochondrial superoxide. We pretreated RGM1 cells with the acidic solutions for 0.5 h and after that treated them with each NSAID for 15 h and found that the exposure to acid and NSAIDs indeed induced cellular injury. We hypothesized that gastric acid and NSAID treatment synergistically induce mitochondrial superoxide production, which induces gastric cellular injury.
authors.affiliation: The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nagano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimokawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells; D005744:Gastric Acid; D005753:Gastric Mucosa / Q000187:drug effects* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013481:Superoxides