Bakuchiol Protects Against Acute Lung Injury in Septic Mice
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ORIGINAL ARTICLE
Bakuchiol Protects Against Acute Lung Injury in Septic Mice Xinxin Zhang,1 Ning Chang,1 Yong Zhang,1 Mingxiang Ye,1 Zhiping Han,1 Jie Li,1 and Jian Zhang1,2
Abstract—Sepsis is a systemic inflammatory reaction that may lead to multiple organ damage and acute lung injury (ALI). Bakuchiol (Bak) has been reported to confer protection against inflammation and oxidative stress. However, its effect on sepsis-induced acute lung injury remains unclear. In the present study, male C57BL/6 mice were subjected to cecal ligation and puncture (CLP), and Bak (15, 30, 60 mg/ kg) was administered intragastrically after 0 and 3 h of surgery. Lung water content was detected. Pathologic changes in lung tissues were evaluated via hematoxylin and eosin (H&E) staining. The levels of myeloperoxidase (MPO), IL-1β, IL-6, and TNF-α were evaluated using ELISA. In addition, expression levels of phosphorylated (p)-IκB, ICAM-1, HMGB1, nitrotyrosine (3-NT), claudin-1, and VE-cadherin were detected using Western blot. Further, IL-1β expression was evaluated using immunofluorescence. SOD activity, contents of MDA, and 8-OHdG were detected to determine the level of oxidative stress. Our results suggested that Bak (60 mg/kg) treatment significantly attenuated pathologic changes and edema in lung tissues and attenuated inflammation and oxidative stress in the lung following sepsis. Additionally, Bak treatment alleviated sepsis-induced lung endothelial barrier disruption. In conclusion, Bak treatment attenuates ALI following sepsis by suppressing inflammation, oxidative stress, and endothelial barrier disruption. Our study indicates that Bak is a potential candidate to treat sepsis-induced ALI. KEY WORDS: sepsis; cecal ligation and puncture; acute lung injury; bakuchiol.
INTRODUCTION Sepsis is a severe inflammatory response to infection and may cause excessive organ damage and death in patients [3, 13, 25]. It has been suggested that various organ injuries are involved in sepsis, including brain, kidney, cardiac, and lung injuries [19, 29, 32, 41]. Sepsis-induced acute lung injury (ALI) is a critical syndrome consisting of
Xinxin Zhang, Ning Chang and Yong Zhang contributed equally to this work. 1
Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, #127 Changle West Road, Xi’an, 710032, People’s Republic of China 2 To whom correspondence should be addressed at Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, #127 Changle West Road, Xi’an, 710032, People’s Republic of China. E-mail: [email protected]
acute hypoxemic respiratory failure with bilateral pulmonary infiltrates, and results in 74,500 deaths and hospitalization of 3.6 million patients each year in the USA [31]. The pathological changes of ALI include impaired gas exchange, dramatic neutrophil infiltration, increased vascular permeability, and parenchymal damage [38]. Despite advances in management strategies, the prognosis of ALI in patients with sepsis is still poor. Sepsis is still the leading cau
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