Targeting reactive oxygen species by edaravone inhalation in a rat hyperoxic lung injury model: role of inflammasome

• Published in: Undersea & hyperbaric medicine Vol. 40; no. 6; p. 505
• Main Authors: Wang, Chen, Ye, Zhouheng, Zheng, Juan, Liu, Kan, Sun, Xuejun, Tao, Hengyi, Liu, Wenwu
• Format: Journal Article
• Language: English
• Published: United States 01-11-2013
• Subjects: Animals; Antioxidants - metabolism; Antipyrine - administration & dosage; Antipyrine - analogs & derivatives; Apoptosis; Body Water; Bronchoalveolar Lavage Fluid - chemistry; Carrier Proteins; Caspase 1 - analysis; Disease Models, Animal; Free Radical Scavengers - administration & dosage; Hyperbaric Oxygenation - adverse effects; Hyperoxia - complications; Interleukin-18 - analysis; Interleukin-1beta - analysis; Lung - chemistry; Lung - pathology; Lung Injury - etiology; Lung Injury - metabolism; Lung Injury - pathology; Lung Injury - prevention & control; Male; Malondialdehyde - analysis; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Cytoplasmic and Nuclear - metabolism
• ISSN: 1066-2936

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.