PMID- 29844231
OWN - NLM
STAT- MEDLINE
DCOM- 20190322
LR  - 20200229
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 94
IP  - 2
DP  - 2018 Aug
TI  - Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon 
      Tetrachloride-Induced Model of Liver Injury.
PG  - 834-841
LID - 10.1124/mol.118.111831 [doi]
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 (CCl(4))-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 CCl(4) Collagen 
      deposition was elevated in the mice treated with both celecoxib and CCl(4) 
      compared with the control or CCl(4)-only groups, as assessed by trichrome 
      staining. Histopathology revealed more extensive fibrosis and cell death in the 
      animals treated with both celecoxib and CCl(4) 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 CCl(4), 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 CCl(4) Oxylipid analysis 
      revealed that celecoxib reduced the level of prostaglandin E(2) relative to the 
      CCl(4) only group. Overall, celecoxib treatment did not decrease liver fibrosis 
      in CCl(4)-treated mice.
CI  - Copyright (c) 2018 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Harris, Todd R
AU  - Harris TR
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California.
FAU - Kodani, Sean
AU  - Kodani S
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California.
FAU - Rand, Amy A
AU  - Rand AA
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California.
FAU - Imai, Denise M
AU  - Imai DM
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California.
FAU - Hwang, Sung Hee
AU  - Hwang SH
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California.
FAU - Hammock, Bruce D
AU  - Hammock BD
AD  - Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center 
      (T.R.H., S.K., A.A.R., J.Y., S.H.H., B.D.H.), and Comparative Pathology 
      Laboratory, School of Veterinary Medicine (D.M.I.), University of California, 
      Davis, California bdhammock@ucdavis.edu.
LA  - eng
GR  - T32 GM067795/GM/NIGMS NIH HHS/United States
GR  - T32 HL086350/HL/NHLBI NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - T32 CA108459/CA/NCI NIH HHS/United States
GR  - U24 DK097154/DK/NIDDK NIH HHS/United States
GR  - R01 DK103616/DK/NIDDK NIH HHS/United States
GR  - R37 ES002710/ES/NIEHS NIH HHS/United States
GR  - T32 GM099608/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180529
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Piperidines)
RN  - 9007-34-5 (Collagen)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.3.2.10 (Ephx2 protein, mouse)
RN  - JCX84Q7J1L (Celecoxib)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/pharmacology
MH  - Carbon Tetrachloride/*toxicity
MH  - Celecoxib/*administration & dosage/pharmacology
MH  - Collagen/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Cyclooxygenase 2 Inhibitors/administration & dosage/pharmacology
MH  - Dinoprostone/metabolism
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/*administration & dosage/pharmacology
MH  - Epoxide Hydrolases/antagonists & inhibitors
MH  - Liver Cirrhosis/*chemically induced/metabolism
MH  - Male
MH  - Mice
MH  - Phenylurea Compounds/administration & dosage/pharmacology
MH  - Piperidines/administration & dosage/pharmacology
PMC - PMC6022802
EDAT- 2018/05/31 06:00
MHDA- 2019/03/23 06:00
PMCR- 2019/08/01
CRDT- 2018/05/31 06:00
PHST- 2018/01/18 00:00 [received]
PHST- 2018/05/18 00:00 [accepted]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2019/03/23 06:00 [medline]
PHST- 2018/05/31 06:00 [entrez]
PHST- 2019/08/01 00:00 [pmc-release]
AID - mol.118.111831 [pii]
AID - MOL_111831 [pii]
AID - 10.1124/mol.118.111831 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2018 Aug;94(2):834-841. doi: 10.1124/mol.118.111831. Epub 2018 May 
      29.