Cepharanthine mitigates pro-inflammatory cytokine response in lung injury induced by hemorrhagic shock/resuscitation in rats

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2015-12, Vol.76 (2), p.442-448
• Main Authors: Kao, Ming-Chang, Yang, Chen-Hsien, Sheu, Joen-Rong, Huang, Chun-Jen
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Benzylisoquinolines - pharmacology; Cytokines - metabolism; Heme Oxygenase (Decyclizing) - metabolism; Heme oxygenase-1; Inflammation Mediators - metabolism; Interleukin; Lung - pathology; Male; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic - metabolism; Tin protoporphyrin; Tumor necrosis factor-α
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2015.09.008

•Hemorrhagic shock/resuscitation increases pulmonary pro-inflammatory cytokines.•Increased pulmonary pro-inflammatory cytokines corresponded to acute lung injury.•Cepharanthine suppressed the pro-inflammatory cytokines and decreased lung injury.•Cepharanthine mitigated pro-inflammatory cytokines via HO-1 dependent pathway. Cepharanthine possesses strong anti-inflammation capacity. We sought to clarify whether cepharanthine could mitigate pro-inflammatory cytokine production in acute lung injury induced by hemorrhagic shock/resuscitation (HS/RES). The involvement of heme oxygenase-1 (HO-1) was also investigated. Male Sprague Dawley rats were allocated to receive HS/RES, HS/RES plus iv cepharanthine or HS/RES plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP) and denoted as the HS/RES, HS/RES+CEP, and HS/RES+CEP+SnPP group, respectively. HS/RES was achieved by blood drawing to lower mean arterial pressure (40–45mmHg for 60min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5h before sacrifice. Arterial blood gas, lung permeability and histologic assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced significant lung injury. Significant increases in pulmonary levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, prostaglandin E2 and cyclooxygenase-2 confirmed that HS/RES induced a significant inflammatory response in the lungs. Cepharanthine significantly attenuated the pulmonary pro-inflammatory cytokine production and lung injury induced by HS/RES. However, the protective effects of cepharanthine were blocked by SnPP, the potent HO-1 activity inhibitor. Cepharanthine significantly mitigates pro-inflammatory cytokine response in acute lung injury induced by HS/RES in rats. The mechanism may involve the HO-1 pathway.