PMID- 27450484
OWN - NLM
STAT- MEDLINE
DCOM- 20170306
LR  - 20171116
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 789
DP  - 2016 Oct 15
TI  - Use of a balanced dual cyclooxygenase-1/2 and 5-lypoxygenase inhibitor in 
      experimental colitis.
PG  - 152-162
LID - S0014-2999(16)30473-3 [pii]
LID - 10.1016/j.ejphar.2016.07.033 [doi]
AB  - Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) play an important role in 
      inflammatory bowel diseases (IBDs). We investigated the effects of flavocoxid, a 
      dual COX/LOX inhibitor, in experimental colitis induced with either 
      dinitrobenzenesulfonic acid (DNBS) or dextrane sulphate sodium (DSS) In the first 
      model, colitis was induced in rats by a single intra-colonic instillation (25mg 
      in 0.8ml 50% ethanol) of DNBS; after 24h animals were randomized to receive 
      orally twice a day, flavocoxid (10mg/kg), zileuton (50mg/kg), or celecoxib 
      (5mg/kg). Sham animals received 0.8ml of saline by a single intra-colonic 
      instillation. Rats were killed 4 days after induction and samples were collected 
      for analysis. In the second model, colitis was induced in rats by the 
      administration of 8% DSS dissolved in drinking water; after 24h animals were 
      randomized to the same above reported treatments. Sham animals received standard 
      drinking water. Rats were killed 5 days after induction and samples were 
      collected for analysis. Flavocoxid, zileuton and celecoxib improved weight loss, 
      reduced colonic myeloperoxydase activity, macroscopic and microscopic damage, and 
      TNF-alpha serum levels. Flavocoxid and celecoxib also reduced malondialdheyde, 6-keto 
      PGF1alpha and PGE-2 levels while flavocoxid and zileuton decreased LTB-4 levels. In 
      addition, flavocoxid treatment improved histological features and apoptosis as 
      compared to zileuton and celecoxib; moreover only flavocoxid reduced TXB2, thus 
      avoiding an imbalance in eicosanoids production. Our results show that flavocoxid 
      has protective effect in IBDs and may represents a future safe treatment for 
      inflammatory bowel diseases.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Pallio, Giovanni
AU  - Pallio G
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Bitto, Alessandra
AU  - Bitto A
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Pizzino, Gabriele
AU  - Pizzino G
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Galfo, Federica
AU  - Galfo F
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Irrera, Natasha
AU  - Irrera N
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Minutoli, Letteria
AU  - Minutoli L
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Arcoraci, Vincenzo
AU  - Arcoraci V
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
FAU - Squadrito, Giovanni
AU  - Squadrito G
AD  - Department of Human Pathology University of Messina, via Consolare Valeria 1 
      Messina, Italy.
FAU - Macri, Antonio
AU  - Macri A
AD  - Department of Human Pathology University of Messina, via Consolare Valeria 1 
      Messina, Italy.
FAU - Squadrito, Francesco
AU  - Squadrito F
AD  - Department of Clinical and Experimental Medicine, Section of Pharmacology 
      University of Messina, via Consolare Valeria 1 Messina, Italy. Electronic 
      address: Francesco.Squadrito@unime.it.
FAU - Altavilla, Domenica
AU  - Altavilla D
AD  - Department of of Biomedical and Dental Sciences and Morphofunctional Imaging, 
      University of Messina, via Consolare Valeria 1 Messina, Italy.
LA  - eng
PT  - Journal Article
DEP - 20160721
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (CD3 Complex)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Drug Combinations)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (flavocoxid)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 58962-34-8 (6-Ketoprostaglandin F1 alpha)
RN  - 8R1V1STN48 (Catechin)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - JCX84Q7J1L (Celecoxib)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - V1L22WVE2S (zileuton)
RN  - X6Q56QN5QC (Hydroxyurea)
SB  - IM
MH  - 6-Ketoprostaglandin F1 alpha/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Arachidonate 5-Lipoxygenase/*metabolism
MH  - Body Weight/drug effects
MH  - CD3 Complex/metabolism
MH  - Catechin/*pharmacology/therapeutic use
MH  - Celecoxib/*pharmacology/therapeutic use
MH  - Colitis/*drug therapy/immunology/metabolism/pathology
MH  - Cyclooxygenase 1/*metabolism
MH  - Cyclooxygenase 2/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/pharmacology/therapeutic use
MH  - Dinoprostone/metabolism
MH  - Drug Combinations
MH  - Eating/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Hydroxyurea/*analogs & derivatives/pharmacology/therapeutic use
MH  - Leukotriene B4/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Lipoxygenase Inhibitors/pharmacology/therapeutic use
MH  - Male
MH  - Neutrophil Infiltration/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thromboxane B2/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Baicalin
OT  - Catechin
OT  - LTB-4
OT  - PGE-2
EDAT- 2016/07/28 06:00
MHDA- 2017/03/07 06:00
CRDT- 2016/07/25 06:00
PHST- 2016/06/08 00:00 [received]
PHST- 2016/07/18 00:00 [revised]
PHST- 2016/07/20 00:00 [accepted]
PHST- 2016/07/25 06:00 [entrez]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2017/03/07 06:00 [medline]
AID - S0014-2999(16)30473-3 [pii]
AID - 10.1016/j.ejphar.2016.07.033 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2016 Oct 15;789:152-162. doi: 10.1016/j.ejphar.2016.07.033. Epub 
      2016 Jul 21.