Celecoxib does not protect against fibrosis and inflammation in a carbon tetrachloride–induced model of liver injury

Todd R. Harris, Sean Kodani, Amy A. Rand, Jun Yang, Denise Imai, Sung Hee Hwang, Bruce D. Hammock

Research output: Contribution to journalArticle

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Abstract

The cyclooxygenase-2 (COX-2) selective inhibitor celecoxib is widely used in the treatment of pain and inflammation. Celecoxib has been explored as a possible treatment of liver fibrosis with contradictory results, depending on the model. The present study reports the effect of celecoxib in a 5-week carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. Celecoxib alone and in combination with inhibitors of the enzyme-soluble epoxide hydrolase (sEH), as well as a dual inhibitor that targets both COX-2 and sEH, were administered via osmotic minipump to mice receiving intraperitoneal injections of CCl4. Collagen deposition was elevated in the mice treated with both celecoxib and CCl4 compared with the control or CCl4-only groups, as assessed by trichrome staining. Histopathology revealed more extensive fibrosis and cell death in the animals treated with both celecoxib and CCl4 compared with all other experimental groups. Although some markers of fibrosis, such as matrix metalloprotease, were unchanged or lowered in the animals treated with both celecoxib and CCl4, overall, hepatic fibrosis was more severe in this group. Cotreatment with celecoxib and an inhibitor of sEH or treatment with a dual inhibitor of COX-2 and sEH decreased the elevated levels of fibrotic markers observed in the group that received both celecoxib and CCl4. Oxylipid analysis revealed that celecoxib reduced the level of prostaglandin E2 relative to the CCl4 only group. Overall, celecoxib treatment did not decrease liver fibrosis in CCl4-treated mice.

Original languageEnglish (US)
Pages (from-to)834-841
Number of pages8
JournalMolecular Pharmacology
Volume94
Issue number2
DOIs
StatePublished - Aug 1 2018

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Celecoxib
Fibrosis
Carbon
Inflammation
Liver
Wounds and Injuries
Epoxide Hydrolases
Liver Cirrhosis
Cyclooxygenase 2 Inhibitors

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Celecoxib does not protect against fibrosis and inflammation in a carbon tetrachloride–induced model of liver injury. / Harris, Todd R.; Kodani, Sean; Rand, Amy A.; Yang, Jun; Imai, Denise; Hwang, Sung Hee; Hammock, Bruce D.

In: Molecular Pharmacology, Vol. 94, No. 2, 01.08.2018, p. 834-841.

Research output: Contribution to journalArticle

Harris, Todd R. ; Kodani, Sean ; Rand, Amy A. ; Yang, Jun ; Imai, Denise ; Hwang, Sung Hee ; Hammock, Bruce D. / Celecoxib does not protect against fibrosis and inflammation in a carbon tetrachloride–induced model of liver injury. In: Molecular Pharmacology. 2018 ; Vol. 94, No. 2. pp. 834-841.
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