title: COX-2 inhibitors are contraindicated for treatment of combined injury.
abstract: Casualties of radiation dispersal devices, nuclear detonation or major ionizing radiation accidents, in addition to radiation exposure, may sustain physical and/or thermal trauma. Radiation exposure plus additional tissue trauma is known as combined injury. There are no definitive therapeutic agents. Cyclooxygenase-2 (COX-2), an inducible enzyme expressed in pathological disorders and radiation injury, plays an important role in inflammation and the production of cytokines and prostaglandin E(2) (PGE(2)) and could therefore affect the outcome for victims of combined injury. The COX-2 inhibitors celecoxib and meloxicam were evaluated for their therapeutic value against combined injury in mice. In survival studies, the COX-2 inhibitors had no beneficial effect on 30-day survival, wound healing or body weight gain after radiation injury alone or after combined injury. Meloxicam accelerated death in both wounded and combined injury mice. These drugs also induced severe hepatic toxicity, exaggerated inflammatory processes, and did not enhance hematopoietic cell regeneration. This study points to potential contraindications for use of COX-2 inhibitors in patients undergoing therapy for radiation injury and combined injury.
authors.affiliation: Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, Maryland 20889-5603, USA.
authors.forename: W
authors.initials: W
authors.lastname: Jiao
authors.forename: J G
authors.initials: JG
authors.lastname: Kiang
authors.forename: L
authors.initials: L
authors.lastname: Cary
authors.forename: T B
authors.initials: TB
authors.lastname: Elliott
authors.forename: T C
authors.initials: TC
authors.lastname: Pellmar
authors.forename: G D
authors.initials: GD
authors.lastname: Ledney
mesh_terms: D000818:Animals; D001835:Body Weight; D000068579:Celecoxib; D000075202:Contraindications; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D005260:Female; D051379:Mice; D011720:Pyrazoles / Q000627:therapeutic use; D011832:Radiation Injuries / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone