Role of Cyclooxygenase Enzymes in a Murine Model of Experimental Cholera

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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 E2 production, mucosal tissue injury, and markers of oxidative stress were measured. Celecoxib and rofecoxib given at 160 μg 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.

Original languageEnglish (US)
Pages (from-to)6234-6242
Number of pages9
JournalInfection and Immunity
Volume71
Issue number11
DOIs
StatePublished - Nov 2003

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Cholera
Cholera Toxin
Prostaglandin-Endoperoxide Synthases
Theoretical Models
Enzymes
Celecoxib
Cyclooxygenase 2
Fluids and Secretions
Cyclooxygenase 1
Oxidative Stress
Arachidonic Acid
Glutathione Disulfide
Cyclooxygenase 2 Inhibitors
Lipid Peroxides
Wounds and Injuries
Dinoprostone
Knockout Mice
Indomethacin
Small Intestine
Protein Isoforms

ASJC Scopus subject areas

  • Immunology

Cite this

Role of Cyclooxygenase Enzymes in a Murine Model of Experimental Cholera. / Gessell-Lee, Deborah L.; Popov, Vsevolod; Boldogh, Istvan; Olano, Juan; Peterson, Johnny.

In: Infection and Immunity, Vol. 71, No. 11, 11.2003, p. 6234-6242.

Research output: Contribution to journalArticle

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