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Updated: Aug 30, 2026
Determination of Tolerable Fatty Acids and Cholera Toxin Concentrations Using Human Intestinal Epithelial Cells and BALB/c Mouse Macrophages
Published on: May 30, 2013
Role of cyclooxygenase enzymes in a murine model of experimental cholera
Deborah L Gessell-Lee1, Vsevolod L Popov, Istvan Boldogh
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA. dlgessel@utmb.edu
Abstract:
Nonsteroidal anti-inflammatory drugs (e.g., indomethacin) inhibit and reduce the fluid secretion responses elicited by cholera toxin (CT), but it has not been conclusively determined which cyclooxygenase (COX) isoform is involved in CT's action. This study evaluated the role of the COX enzymes and their arachidonic acid metabolites in experimental cholera. Swiss-Webster mice were dosed with celecoxib and rofecoxib and challenged with CT in ligated small intestinal loops, and intestinal segments from mice deficient in COX-1 and COX-2 were challenged with CT. The effects of CT on fluid accumulation, prostaglandin E(2) production, mucosal tissue injury, and markers of oxidative stress were measured. Celecoxib and rofecoxib given at 160 micro g per mouse inhibited CT-induced fluid accumulation by 48% and 31%, respectively, but there was no significant difference among cox-1(-/-) and cox-2(-/-) mice in response to CT compared to wild-type controls. CT elevated tissue levels of oxidized glutathione and lipid peroxides and elicited small intestinal tissue injury in two of five cox-1(-/-) and four of five cox-2(-/-) mice. A role for COX-2 in CT's mechanism of action has previously been suggested by the effectiveness of COX-2 inhibitors in reducing CT-induced fluid secretion, but CT challenge of COX-1 and COX-2 knockout mice did not corroborate the pharmacological data. The results of this study show that CT induced oxidative stress in COX-deficient mice and suggest a tissue-protective role for arachidonic acid metabolites in the small intestine against oxidative stress.
Insights
Cyclooxygenase (COX) inhibitors reduce cholera toxin (CT)-induced fluid secretion, but this study found no significant difference in CT response in COX-deficient mice. CT induced oxidative stress in these mice, suggesting a protective role for arachidonic acid metabolites.
Area of Science:
- Gastroenterology
- Pharmacology
- Molecular Biology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit fluid secretion induced by cholera toxin (CT).
- The specific cyclooxygenase (COX) isoform mediating this response to CT has not been definitively identified.
- Arachidonic acid metabolites are implicated in intestinal inflammatory processes.
Purpose of the Study:
- To investigate the roles of COX-1 and COX-2 enzymes in experimental cholera.
- To determine the involvement of arachidonic acid metabolites in CT-induced intestinal responses.
- To assess the impact of CT on fluid accumulation, prostaglandin E(2) production, tissue injury, and oxidative stress in COX-deficient mice.
Main Methods:
- Administration of selective COX-2 inhibitors (celecoxib, rofecoxib) to Swiss-Webster mice challenged with CT.
- Challenging ligated intestinal loops from COX-1 knockout (cox-1(-/-)) and COX-2 knockout (cox-2(-/-)) mice with CT.
- Measurement of fluid accumulation, prostaglandin E(2) levels, mucosal injury, and oxidative stress markers (oxidized glutathione, lipid peroxides).
Main Results:
- Celecoxib and rofecoxib partially inhibited CT-induced fluid accumulation.
- No significant difference in CT response was observed between COX-deficient mice and wild-type controls.
- CT challenge led to increased oxidative stress markers and intestinal injury in COX-deficient mice.
Conclusions:
- Pharmacological data suggesting a role for COX-2 in CT action were not corroborated by experiments with COX-deficient mice.
- Cholera toxin induces oxidative stress in the small intestine, even in the absence of functional COX enzymes.
- Arachidonic acid metabolites may play a tissue-protective role against CT-induced oxidative stress in the small intestine.
