Thioredoxin-1 attenuates indomethacin-induced gastric mucosal injury in mice.

Abstract

Indomethacin is one of non-steroidal anti-inflammatory drugs that are commonly used clinically and often cause gastric mucosal injury as a side effect. Generation of reactive oxygen species (ROS) and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric mucosal injury. Thioredoxin-1 (Trx-1) is a small redox-active protein with anti-oxidative activity and redox-regulating functions. The aim of this study was to investigate the protective effect of Trx-1 against indomethacin-induced gastric mucosal injury. Trx-1 transgenic mice displayed less gastric mucosal damage than wild type (WT) C57BL/6 mice after intraperitoneal administration of indomethacin. Administration of recombinant human Trx-1 (rhTrx-1) or transfection of the Trx-1 gene reduced indomethacin-induced cytotoxicity in rat gastric epithelial RGM-1 cells. Pretreatment with rhTrx-1 suppressed indomethacininduced ROS production and downregulation of phosphorylated Akt in RGM-1 cells. Survivin, a member of inhibitors of apoptosis proteins family, was downregulated by indomethacin, which was suppressed in Trx-1 transgenic mice or by administration of rhTrx-1 in RGM-1 cells. Trx-1 inhibits indomethacin-induced apoptotic signaling and gastric ulcer formation, suggesting that it may have a preventive and therapeutic potential against indomethacin-induced gastric injury.

• Authors: Aiguo Tan, Hajime Nakamura, Norihiko Kondo, Masaki Tanito, Yong-Won Kwon, M Kaimul Ahsan, Hirofumi Matsui, Makiko Narita, Junji Yodoi
• Journal: Free radical research (Free Radic Res) Vol. 41 Issue 8 Pg. 861-9 (Aug 2007) ISSN: 1071-5762 [Print] England
• PMID: 17654042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Reactive Oxygen Species
• Recombinant Proteins
• Txn1 protein, mouse
• Thioredoxins
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (antagonists & inhibitors, toxicity)
• Apoptosis (drug effects, genetics)
• Cell Line
• Gastric Mucosa (drug effects, metabolism)
• Indomethacin (antagonists & inhibitors, toxicity)
• Mice
• Mice, Transgenic
• Rats
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Recombinant Proteins (genetics, pharmacology)
• Thioredoxins (genetics, metabolism, pharmacology)