TY - JOUR
T1 - Poloxamer 188 Attenuates Ischemia-Reperfusion-Induced Lung Injury by Maintaining Cell Membrane Integrity and Inhibiting Multiple Signaling Pathways
AU - Tang, Shih En
AU - Liao, Wen I.
AU - Pao, Hsin Ping
AU - Hsu, Chin Wang
AU - Wu, Shu Yu
AU - Huang, Kun Lun
AU - Chu, Shi Jye
N1 - Funding Information:
This study was supported, in part, by grants MOST 109-2314-B-016-028 from Ministry of Science and Technology, Taiwan, TSGH-2-C109-109-2314-B-016-028, TSGH-D-109078 and TSGH-C108-075 from Tri-Service General Hospital, and MAB-109-021, MAB-108-016, and MAB-107-011 from Ministry of National Defense-Medical Affairs Bureau, Taiwan.
Publisher Copyright:
© Copyright © 2021 Tang, Liao, Pao, Hsu, Wu, Huang and Chu.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Background: Poloxamer 188 (P188) possesses anti-inflammatory properties and can help to maintain plasma membrane function. P188 has been reported to exert beneficial effects in the treatment of various disorders. However, the effects of P188 in ischemia/reperfusion (IR)-induced acute lung injury have not been examined. Methods: We investigated the ability of P188 to attenuate IR-induced acute lung injury in rats and hypoxia/reoxygenation (HR) injury in murine epithelial cells. Isolated perfused rat lungs were exposed to 40 min ischemia followed by 60 min reperfusion to induce IR injury. Results: IR led to lung edema, increased pulmonary arterial pressure, promoted lung tissue inflammation and oxidative stress, and upregulated the levels of TNF-α, IL-6 and CINC-1, and increased Lactic dehydrogenase (LDH) activity in bronchoalveolar lavage fluid. IR also downregulated the levels of inhibitor of κB (IκB-α), upregulated nuclear factor (NF)-κB (NF-κB), and promoted apoptosis in lung tissues. P188 significantly suppressed all these effects. In vitro, P188 also exerted a similar effect in murine lung epithelial cells exposed to HR. Furthermore, P188 reduced the number of propidium iodide-positive cells, maintained cell membrane integrity, and enhanced cell membrane repair following HR. Conclusion: We conclude that P188 protects against lung IR injury by suppressing multiple signaling pathways and maintaining cell membrane integrity.
AB - Background: Poloxamer 188 (P188) possesses anti-inflammatory properties and can help to maintain plasma membrane function. P188 has been reported to exert beneficial effects in the treatment of various disorders. However, the effects of P188 in ischemia/reperfusion (IR)-induced acute lung injury have not been examined. Methods: We investigated the ability of P188 to attenuate IR-induced acute lung injury in rats and hypoxia/reoxygenation (HR) injury in murine epithelial cells. Isolated perfused rat lungs were exposed to 40 min ischemia followed by 60 min reperfusion to induce IR injury. Results: IR led to lung edema, increased pulmonary arterial pressure, promoted lung tissue inflammation and oxidative stress, and upregulated the levels of TNF-α, IL-6 and CINC-1, and increased Lactic dehydrogenase (LDH) activity in bronchoalveolar lavage fluid. IR also downregulated the levels of inhibitor of κB (IκB-α), upregulated nuclear factor (NF)-κB (NF-κB), and promoted apoptosis in lung tissues. P188 significantly suppressed all these effects. In vitro, P188 also exerted a similar effect in murine lung epithelial cells exposed to HR. Furthermore, P188 reduced the number of propidium iodide-positive cells, maintained cell membrane integrity, and enhanced cell membrane repair following HR. Conclusion: We conclude that P188 protects against lung IR injury by suppressing multiple signaling pathways and maintaining cell membrane integrity.
KW - acute lung injury
KW - hypoxia/reoxygenation
KW - ischemia-reperfusion
KW - membrane integrity
KW - poloxamer 188
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U2 - 10.3389/fphar.2021.650573
DO - 10.3389/fphar.2021.650573
M3 - Article
AN - SCOPUS:85111568777
SN - 1663-9812
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 650573
ER -