title: A novel platelet activating factor antagonist, SM-12502, attenuates endotoxin-induced disseminated intravascular coagulation and acute pulmonary vascular injury by inhibiting TNF production in rats.
abstract: Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-alpha by ET-stimulated monocytes in vitro. These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production.
authors.affiliation: Department of Medicine, Kumamoto University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Okajima
authors.forename: M
authors.initials: M
authors.lastname: Uchiba
authors.forename: M
authors.initials: M
authors.lastname: Johno
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: K
authors.initials: K
authors.lastname: Takatsuki
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011651:Pulmonary Artery / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012127:Respiratory Distress Syndrome, Newborn / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D013844:Thiazoles / Q000008:administration & dosage*; D053778:Thiazolidines
chemical_list: D004731:Endotoxins; D010972:Platelet Activating Factor; D013844:Thiazoles; D053778:Thiazolidines; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one