title: Targeting reactive oxygen species by edaravone inhalation in a rat hyperoxic lung injury model: role of inflammasome.
abstract: This study was undertaken to investigate the effect of edaravone inhalation on inflammasome activation in a rat hyperoxia-induced lung injury (HILI) model. Sprague Dawley rats (n = 61) were randomly assigned into three groups: Control group, HILI group and Edaravone (Eda) group. Rats in the Control group breathed room air, but those in the HILI group and Eda group were exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) for six hours. Immediately after HILI, rats in the Eda group received inhalation of aerosol edaravone at 0.5 mg/ml for 30 minutes. Twenty-four hours later, rats were sacrificed. The bronchoalveolar lavage fluid (BALF) and lungs were obtained for detection of oxidative stress, IL-1beta, IL-18 and caspase-1; the lungs were collected for HE staining and TUNEL staining. The pathological features of the lungs of rats in the Eda group were significantly improved when compared with the HILI group, accompanied by reduction in apoptotic cells. In addition, in the Eda group, the malonyldialdehyde (MDA) was reduced and total antioxidant capacity (T-AOC) was increased significantly in the lung and BALF when compared with the HILI group (P < 0.05 for both). Moreover, the contents of IL-1beta, IL-18 and caspase-1 in the lung and BALF, downstream factors of inflammasome, were also dramatically lower in the Eda group than in the HILI group (P < 0.05 for all). These findings suggest that edaravone may inhibit inflammasome activation due to its anti-oxidative capacity exerting a protective effect on HILI.
authors.affiliation: Division of Magnetic Resonance Imaging, Department of Radiology, Affiliated Huadong Hospital of Fudan University, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Diving Medicine, Second Military Medical University, Yangpu District, Shanghai, PR China.
authors.forename: Zhouheng
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Diving Medicine, Second Military Medical University, Yangpu District, Shanghai, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Diving Medicine, Second Military Medical University, Yangpu District, Shanghai, PR China.
authors.forename: Kan
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Diving Medicine, Second Military Medical University, Yangpu District, Shanghai, PR China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Diving Medicine, Second Military Medical University, Yangpu District, Shanghai, PR China.
authors.forename: Hengyi
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Diving Medicine, Second Military Medical University, Yangpu District, Shanghai, PR China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017209:Apoptosis; D001834:Body Water; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002352:Carrier Proteins; D020170:Caspase 1 / Q000032:analysis; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006931:Hyperbaric Oxygenation / Q000009:adverse effects; D018496:Hyperoxia / Q000150:complications*; D020382:Interleukin-18 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D016166:Free Radical Scavengers; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D008315:Malondialdehyde; D020170:Caspase 1; D000077553:Edaravone; D000983:Antipyrine