Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon Tetrachloride-Induced Model of Liver Injury

Mol Pharmacol. 2018 Aug;94(2):834-841. doi: 10.1124/mol.118.111831. Epub 2018 May 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carbon Tetrachloride / toxicity*
  • Celecoxib / administration & dosage*
  • Celecoxib / pharmacology
  • Collagen / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / pharmacology
  • Epoxide Hydrolases / antagonists & inhibitors
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / metabolism
  • Male
  • Mice
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / pharmacology
  • Piperidines / administration & dosage
  • Piperidines / pharmacology


  • 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Enzyme Inhibitors
  • Phenylurea Compounds
  • Piperidines
  • Collagen
  • Carbon Tetrachloride
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Epoxide Hydrolases
  • Ephx2 protein, mouse
  • Celecoxib
  • Dinoprostone