title: Effect of evening primrose oil and ω-3 polyunsaturated fatty acids on the cardiovascular risk of celecoxib in rats.
abstract: Experimental data raised the specter of increased cardiovascular risk with selective cyclooxygenase-2 inhibitors. The study aimed to investigate the cardiovascular risk caused by celecoxib by studying its effect on blood pressure (BP) and thrombogenesis in rats. We tested the possible protective effects of evening primrose oil (EPO) or ω-3 polyunsaturated fatty acids (n-3 PUFAs). Male Wistar rats were assigned to the following groups: vehicle, celecoxib, celecoxib/n-3 PUFAs, celecoxib/EPO, n-3 PUFAs, and EPO. The rats were treated with celecoxib (20 mg·kg(-1)·d(-1)) by gastric gavage for 6 weeks. The mean BP was recorded, and blood samples were collected for testing prothrombin time and activated partial thromboplastin time. Platelet aggregation assay and collagen-induced platelet consumption test were used as models of thrombogenesis. Celecoxib increased the BP without affecting coagulation parameters and accelerated thrombogenesis by increasing platelet aggregation and collagen-induced thrombocytopenia. EPO and n-3 PUFAs decreased the celecoxib-induced elevation in BP. Although EPO significantly decreased platelet aggregation and collagen-induced thrombocytopenia, n-3 PUFAs did not. Celecoxib elevated BP and increased the risk of thrombogenesis in rats. A combination of celecoxib and the selected natural supplements is suggested as a novel approach to minimize cardiovascular risk caused by celecoxib.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Egypt. Sawsan_zaytoon@pharm.suez.edu.eg
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Moustafa
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Mosaad
authors.forename: Naglaa F
authors.initials: NF
authors.lastname: El-Orabi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D000068579:Celecoxib; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D008041:Linoleic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D031665:Oenothera biennis / Q000502:physiology*; D010938:Plant Oils / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D013449:Sulfonamides / Q000633:toxicity*; D013927:Thrombosis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D016896:Treatment Outcome; D017965:gamma-Linolenic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D008041:Linoleic Acids; D010938:Plant Oils; D011720:Pyrazoles; D013449:Sulfonamides; C028498:evening primrose oil; D017965:gamma-Linolenic Acid; D000068579:Celecoxib