PMID- 31293429
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for 
      NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis.
PG  - 731
LID - 10.3389/fphar.2019.00731 [doi]
LID - 731
AB  - Polyunsaturated fatty acids (PUFAs) including epoxide-modified omega-3 and omega-6 fatty 
      acids are made via oxidation to create highly polarized carbon-oxygen bonds 
      crucial to their function as signaling molecules. A critical PUFA, arachidonic 
      acid (ARA), is metabolized to a diverse set of lipids signaling molecules through 
      cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 epoxygenase, or 
      cytochrome P450 hydroxylase; however, the majority of ARA is metabolized into 
      anti-inflammatory epoxides via cytochrome P450 enzymes. These short-lived epoxide 
      lipids are rapidly metabolized or inactivated by the soluble epoxide hydrolase 
      (sEH) into diol-containing products. sEH inhibition or knockout has been a 
      practical approach to study the biology of the epoxide lipids, and has been shown 
      to effectively treat inflammatory conditions in the preclinical models including 
      gastrointestinal ulcers and colitis by shifting oxylipins to epoxide profiles, 
      inhibiting inflammatory cell infiltration and activation, and enhancing 
      epithelial cell defense via increased mucin production, thus providing further 
      evidence for the role of sEH as a pro-inflammatory protein. Non-steroidal 
      anti-inflammatory drugs (NSAIDs) with COX-inhibitor activity are among the most 
      commonly used analgesics and have demonstrated applications in the management of 
      cardiovascular disease and intriguingly cancer. Major side effects of NSAIDs 
      however are gastrointestinal ulcers which frequently precludes their long-term 
      application. In this review, we hope to bridge the gap between NSAID toxicity and 
      sEH-mediated metabolic pathways to focus on the role of epoxy fatty acid 
      metabolic pathway of PUFAs in NSAIDS-ulcer formation and healing as well as 
      inflammation-related carcinogenesis. Specifically we address the potential 
      application of sEH inhibition to enhance ulcer healing at the site of 
      inflammation via their activity on altered lipid signaling, mitochondrial 
      function, and diminished reactive oxygen species, and further discuss the 
      significance of dual COX and sEH inhibitor in anti-inflammation and 
      carcinogenesis.
FAU - Jones, Ryan D
AU  - Jones RD
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
FAU - Liao, Jie
AU  - Liao J
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
FAU - Tong, Xin
AU  - Tong X
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
FAU - Xu, Dandan
AU  - Xu D
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
FAU - Sun, Leyu
AU  - Sun L
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
FAU - Li, Haonan
AU  - Li H
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
FAU - Yang, Guang-Yu
AU  - Yang GY
AD  - Department of Pathology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, United States.
LA  - eng
GR  - R01 CA104741/CA/NCI NIH HHS/United States
GR  - R01 CA137467/CA/NCI NIH HHS/United States
GR  - R01 CA172431/CA/NCI NIH HHS/United States
GR  - R01 DK107767/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20190625
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6603234
OTO - NOTNLM
OT  - carcinogenesis
OT  - inflammation
OT  - non-steroidal anti-inflammatory drug
OT  - oxylipin
OT  - soluble epoxide hydrolase
EDAT- 2019/07/12 06:00
MHDA- 2019/07/12 06:01
PMCR- 2019/06/25
CRDT- 2019/07/12 06:00
PHST- 2018/12/18 00:00 [received]
PHST- 2019/06/05 00:00 [accepted]
PHST- 2019/07/12 06:00 [entrez]
PHST- 2019/07/12 06:00 [pubmed]
PHST- 2019/07/12 06:01 [medline]
PHST- 2019/06/25 00:00 [pmc-release]
AID - 10.3389/fphar.2019.00731 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Jun 25;10:731. doi: 10.3389/fphar.2019.00731. eCollection 
      2019.