PMID- 35447388
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220602
IS  - 1532-2661 (Electronic)
IS  - 0034-5288 (Linking)
VI  - 147
DP  - 2022 Oct
TI  - Effects of cyclooxygenase and soluble epoxide hydrolase inhibitors on apoptosis 
      of cultured primary equine chondrocytes.
PG  - 44-49
LID - S0034-5288(22)00103-5 [pii]
LID - 10.1016/j.rvsc.2022.04.002 [doi]
AB  - BACKGROUND: Apoptosis is an important mechanism underlying chondrocyte loss in 
      osteoarthritis that could be affected by modulation of lipid signaling via 
      inhibition of cyclooxygenases (COX) and soluble epoxide hydrolase (sEH). 
      OBJECTIVE: To determine the impact of inhibiting COX and sEH alone or in 
      combination on apoptosis of equine chondrocytes. METHODS: Cultured primary equine 
      chondrocytes were subjected to serum deprivation or incubation with 1 mug/ml 
      tunicamycin for 24 h to induce apoptosis via caspase activation and endoplasmic 
      reticulum (ER) stress, respectively. Cells were treated with the non-selective 
      COX inhibitor phenylbutazone, the COX-2 selective inhibitor firocoxib and the sEH 
      inhibitor t-TUCB alone or in combination. The inhibitors were used at 
      half-maximal (IC(50)), 80% of maximal (IC(80)) and 10-fold the 80% inhibitory 
      concentration (10xIC(80)) for the equine enzymes. Apoptosis was quantified via 
      ELISA technique. Data were analyzed with unpaired two-tailed t-test or one-way 
      ANOVA followed by Bonferroni's post-hoc while correcting for multiple comparisons 
      via statistical hypothesis testing. P < 0.05 was considered significant. RESULTS: 
      In the caspase model, 10xIC(80)t-TUCB significantly decreased whereas 10xIC(80) 
      phenylbutazone significantly enhanced apoptosis. Apoptosis enhancement by 
      phenylbutazone was significantly attenuated by concurrent 10xIC(80)t-TUCB. The 
      remaining treatments and concentrations had no effect on apoptosis development. 
      In the ER stress model, IC(50) and IC(80) phenylbutazone and firocoxib 
      significantly enhanced apoptosis, which was fully prevented by concurrent 
      10xIC(80)t-TUCB. MAIN LIMITATIONS: In vitro findings that will need to be 
      verified in vivo. CONCLUSIONS: Chondrocyte apoptosis caused by ER stress can be 
      enhanced by COX inhibition but prevented by concurrent inhibition of sEH.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Walters, B
AU  - Walters B
AD  - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, 
      University of Minnesota, Saint Paul, MN 55108, USA.
FAU - Trumble, T N
AU  - Trumble TN
AD  - Department of Veterinary Population Medicine, College of Veterinary Medicine, 
      University of Minnesota, Saint Paul, MN 55108, USA.
FAU - Wendt-Hornickle, E
AU  - Wendt-Hornickle E
AD  - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, 
      University of Minnesota, Saint Paul, MN 55108, USA.
FAU - Kennedy, M
AU  - Kennedy M
AD  - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, 
      University of Minnesota, Saint Paul, MN 55108, USA.
FAU - Guedes, Agp
AU  - Guedes A
AD  - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, 
      University of Minnesota, Saint Paul, MN 55108, USA. Electronic address: 
      guede003@umn.edu.
LA  - eng
PT  - Journal Article
DEP - 20220412
PL  - England
TA  - Res Vet Sci
JT  - Research in veterinary science
JID - 0401300
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.4.22.- (Caspases)
RN  - GN5P7K3T8S (Phenylbutazone)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Caspases
MH  - *Chondrocytes
MH  - Cyclooxygenase 2
MH  - *Epoxide Hydrolases
MH  - Horses
MH  - Phenylbutazone
OTO - NOTNLM
OT  - Apoptosis
OT  - COX-inhibitors
OT  - Chondrocyte
OT  - Horse
OT  - Osteoarthritis
EDAT- 2022/04/22 06:00
MHDA- 2022/06/03 06:00
CRDT- 2022/04/21 20:12
PHST- 2021/11/11 00:00 [received]
PHST- 2022/02/24 00:00 [revised]
PHST- 2022/04/08 00:00 [accepted]
PHST- 2022/04/22 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/04/21 20:12 [entrez]
AID - S0034-5288(22)00103-5 [pii]
AID - 10.1016/j.rvsc.2022.04.002 [doi]
PST - ppublish
SO  - Res Vet Sci. 2022 Oct;147:44-49. doi: 10.1016/j.rvsc.2022.04.002. Epub 2022 Apr 
      12.