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 language | English (US) |
|---|---|
| Pages (from-to) | 834-841 |
| Number of pages | 8 |
| Journal | Molecular Pharmacology |
| Volume | 94 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Celecoxib does not protect against fibrosis and inflammation in a carbon tetrachloride–induced model of liver injury
AU - Harris, Todd R.
AU - Kodani, Sean
AU - Rand, Amy A.
AU - Yang, Jun
AU - Imai, Denise
AU - Hwang, Sung Hee
AU - Hammock, Bruce D.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85049391316&partnerID=8YFLogxK
U2 - 10.1124/mol.118.111831
DO - 10.1124/mol.118.111831
M3 - Article
C2 - 29844231
AN - SCOPUS:85049391316
VL - 94
SP - 834
EP - 841
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 2
ER -