title: Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock.
abstract: Objectives. The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARγ plays an important role in maraviroc-mediated lung protection following trauma-hemorrhage. Methods. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγ inhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n = 8 rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey's testing were used for statistical analysis. Results. Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1β levels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury. Conclusion. These results suggest that PPARγ might play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Huang-Ping
authors.identifier: 0000-0002-3030-0560
authors.initials: HP
authors.lastname: Yu
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D003510:Cyclohexanes / Q000494:pharmacology*; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D000077592:Maraviroc; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc