title: Use of a balanced dual cyclooxygenase-1/2 and 5-lypoxygenase inhibitor in experimental colitis.
abstract: 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-α serum levels. Flavocoxid and celecoxib also reduced malondialdheyde, 6-keto PGF1α 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pallio
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pizzino
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Galfo
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arcoraci
authors.affiliation: Department of Human Pathology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Squadrito
authors.affiliation: Department of Human Pathology University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macrì
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology University of Messina, via Consolare Valeria 1 Messina, Italy. Electronic address: Francesco.Squadrito@unime.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.affiliation: Department of of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria 1 Messina, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D017252:CD3 Complex / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology* / Q000627:therapeutic use; D000068579:Celecoxib / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004338:Drug Combinations; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C544478:flavocoxid; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D002392:Catechin; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone; C063449:zileuton; D006918:Hydroxyurea
keywords: Apoptosis; Baicalin; Catechin; LTB-4; PGE-2