title: Evening primrose oil or forskolin ameliorates celecoxib-enhanced upregulation of tissue factor expression in mice subjected to lipopolysaccharide-induced endotoxemia.
abstract: Celecoxib, a selective cyclooxygenase-2 inhibitor, produces thrombotic events in patients predisposed to cardiovascular risk factors. One theory reported an increase in endothelial expression of tissue factor (TF) as a predisposing factor. This work explored the effect of evening primrose oil (EPO), a source of prostaglandin E1, and forskolin (a cyclic adenosine monophosphate stimulator) against the prothrombotic effect of celecoxib in mice. Lipopolysaccharide mouse model of endotoxemia was used to induce an upregulation of TF activity. Male mice received celecoxib (25 mg/kg), celecoxib plus EPO, or celecoxib plus forskolin for 4 weeks and then subjected to a prothrombotic challenge in the form of an intraperitoneal injection of lipopolysaccharide. Results showed an increase in plasma TF activity, endothelial TF expression, and thrombin-antithrombin (TAT) but lower antithrombin III (ATIII) level in mice that received celecoxib in comparison to those that received the vehicle. Adding EPO or forskolin to celecoxib regimen significantly decreased the prothrombotic effect of celecoxib. A positive correlation (r = 0.8501) was found between TF activity and TAT. Co-administration of EPO or forskolin decreased the activity of TF and mitigated the prothrombotic effect of celecoxib. Therefore, these combinations may have the utility to abrogate the prothrombotic adverse effect of celecoxib in clinical setting.
authors.affiliation: Department of Pharmaceutical Inspection, Ministry of Health, Ismailia, 41111, Egypt.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Mosaad
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. Sawsan_zaytoon@pharm.suez.edu.eg.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk City, Kingdom of Saudi Arabia. Sawsan_zaytoon@pharm.suez.edu.eg.
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
authors.affiliation: Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.
authors.forename: Amal A M
authors.initials: AA
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt.
authors.forename: Dina M
authors.initials: DM
authors.lastname: Abo-Elmatty
authors.affiliation: Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt.
authors.forename: Amani A
authors.initials: AA
authors.lastname: El-Baz
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Moustafa
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D000068579:Celecoxib; D005576:Colforsin / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008041:Linoleic Acids / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D031665:Oenothera biennis; D010447:Peptide Hydrolases / Q000097:blood; D010938:Plant Oils / Q000494:pharmacology*; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D015854:Up-Regulation; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005343:Fibrinolytic Agents; D008041:Linoleic Acids; D008070:Lipopolysaccharides; D010938:Plant Oils; C046193:antithrombin III-protease complex; C440499:lipopolysaccharide, Escherichia coli O111 B4; D005576:Colforsin; C028498:evening primrose oil; D017965:gamma-Linolenic Acid; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D000068579:Celecoxib
keywords: Celecoxib; Evening primrose oil; Forskolin; Lipopolysaccharide; Thrombosis; Tissue factor