TY - JOUR
T1 - Cepharanthine mitigates pro-inflammatory cytokine response in lung injury induced by hemorrhagic shock/resuscitation in rats
AU - Kao, Ming Chang
AU - Yang, Chen Hsien
AU - Sheu, Joen Rong
AU - Huang, Chun Jen
N1 - Funding Information:
This work was supported by a grant from the Taipei Tzu Chi Hospital (TCRD-TPE-101-37) awarded to MCK.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background: 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. Methods: 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 (40-45 mmHg for 60 min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5. h before sacrifice. Results: 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. Conclusion: 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.
AB - Background: 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. Methods: 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 (40-45 mmHg for 60 min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5. h before sacrifice. Results: 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. Conclusion: 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.
KW - Anti-inflammatory
KW - Heme oxygenase-1
KW - Interleukin
KW - Tin protoporphyrin
KW - Tumor necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=84943813435&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943813435&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2015.09.008
DO - 10.1016/j.cyto.2015.09.008
M3 - Article
C2 - 26375521
AN - SCOPUS:84943813435
SN - 1043-4666
VL - 76
SP - 442
EP - 448
JO - Cytokine
JF - Cytokine
IS - 2
ER -