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Updated: May 2, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine
M Sandoval1, X Liu, E E Mannick
1Department of Pediatrics, Louisiana State University School of Medicine, New Orleans 70112, USA.
Background & Aims:
Peroxynitrite (PN), a potent oxidant, has been implicated in the pathogenesis of gut inflammation and epithelial cell apoptosis. The aim of this study was to investigate mesalamine, a standard therapy for inflammatory bowel disease, to see if it attenuates PN-induced cytotoxicity in human intestinal epithelial cells and if mesalamine directly interacts with PN or its precursor, nitric oxide.
Methods:
T84 and HT29 cells were divided in several protocols: mesalamine was administered 2 hours before, simultaneously, or 30 minutes after PN. T84 cells, grown in filter chamber inserts, were used to determine if basolateral or apical administration of PN initiated apoptosis and epithelial barrier function. The effects of mesalamine on PN decomposition and NO half-life were determined.
Results:
Mesalamine resulted in a dose-dependent decrease in PN-induced apoptosis, whether mesalamine was administered before (>10 micromol/L; IC50, 16 micromol/L), simultaneously (25-200 micromol/L; IC50, 24 micromol/L), or 30 minutes (200 micromol/L) after PN exposure. Mesalamine protected the epithelial barrier function of T84 cells against PN. Mesalamine rapidly degraded PN, whereas the half-life of NO was not affected.
Conclusions:
The beneficial effects of mesalamine in the treatment of inflammatory bowel disease may involve an attenuation of PN-induced cell injury and apoptosis through direct and indirect mechanisms without affecting NO levels.
Insights
Mesalamine reduces cell damage and apoptosis caused by peroxynitrite (PN) in gut inflammation. This standard inflammatory bowel disease therapy directly degrades PN without affecting nitric oxide (NO) levels.
Area of Science:
- Gastroenterology
- Cell Biology
- Pharmacology
Background:
- Peroxynitrite (PN) is a key factor in inflammatory bowel disease (IBD) pathogenesis, causing gut inflammation and epithelial cell apoptosis.
- Mesalamine is a widely used treatment for IBD.
Purpose of the Study:
- To investigate if mesalamine mitigates PN-induced cytotoxicity in human intestinal epithelial cells.
- To determine if mesalamine interacts with PN or its precursor, nitric oxide (NO).
Main Methods:
- Human intestinal epithelial cell lines (T84 and HT29) were treated with mesalamine before, during, or after PN exposure.
- Apoptosis and epithelial barrier function were assessed in T84 cells.
- Mesalamine's effect on PN decomposition and NO half-life was measured.
Main Results:
- Mesalamine demonstrated a dose-dependent reduction in PN-induced apoptosis and protected epithelial barrier function.
- Mesalamine rapidly degraded PN.
- The half-life of NO remained unaffected by mesalamine treatment.
Conclusions:
- Mesalamine's therapeutic benefits in IBD may stem from its ability to attenuate PN-induced cell injury and apoptosis.
- These protective effects appear to involve direct and indirect mechanisms.
- Mesalamine's action does not influence NO levels.
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