NSAIDs induce both necrosis and apoptosis in guinea pig gastric mucosal cells in primary culture

A major clinical problem encountered with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is gastropathy. In this study, we examined, using guinea pig gastric mucosal cells in primary culture, how NSAIDs damage gastric mucosal cells. The short-term treatment of cells wi...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2001-10, Vol.281 (4), p.G1092-G1100
Main Authors: Tomisato, W, Tsutsumi, S, Rokutan, K, Tsuchiya, T, Mizushima, T
Format: Article
Language:English
Subjects:
Amino Acid Chloromethyl Ketones - pharmacology
Animals
Anti-Inflammatory Agents, Non-Steroidal - adverse effects
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Apoptosis - drug effects
Apoptosis - physiology
Aspirin - pharmacology
Caspase Inhibitors
Caspases - metabolism
Cell Survival - drug effects
Cells, Cultured
Cycloheximide - pharmacology
Cysteine Proteinase Inhibitors - metabolism
DNA Fragmentation
Gastric Mucosa - cytology
Gastric Mucosa - drug effects
Gastric Mucosa - pathology
Glucosamine - metabolism
Guinea Pigs
Indomethacin - pharmacology
Male
Microscopy, Fluorescence
Necrosis
Protein Synthesis Inhibitors - pharmacology
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A major clinical problem encountered with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is gastropathy. In this study, we examined, using guinea pig gastric mucosal cells in primary culture, how NSAIDs damage gastric mucosal cells. The short-term treatment of cells with high concentrations of indomethacin decreased cell viability in the absence of apoptotic DNA fragmentation, chromatin condensation, or caspase activation. Cells lost membrane integrity with this short-term indomethacin treatment, suggesting that indomethacin induced necrosis under these conditions. In contrast, the long-term treatment of cells with low concentrations of indomethacin decreased cell viability and was accompanied by apoptotic DNA fragmentation, chromatin condensation, and caspase activation. Pretreatment of cells with inhibitors of caspases or protein synthesis suppressed cell death caused by long-term indomethacin treatment, suggesting that apoptosis was induced when the inhibitors were not present. These results imply that NSAIDs cause gastric mucosal damage through both necrosis and apoptosis of gastric mucosal cells.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2001.281.4.g1092