Dexamethasone treatment attenuates early seawater instillation-induced acute lung injury in rabbits

Ding, Xiaohu; Duan, Yun-you; Chao-sheng, Peng; Feng, Hao; Zhou, Pingkun; Meng, Jiguang; Zhiqian, Xue; Xu, Qiong

doi:10.1016/j.phrs.2006.01.006

Cited by 38 publications

(36 citation statements)

References 34 publications

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“…The rabbit models of intratracheal instillation of seawater-induced lung injury were prepared using a modification of the method described by Xinmin et al [2]. Seawater was prepared according to the Standard of the Third Institute of Oceanography of the State Ocean Bureau [22].…”

Section: Animals and Methodsmentioning

confidence: 99%

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Urinary Trypsin Inhibitor Attenuates Seawater-Induced Acute Lung Injury by Influencing the Activities of Nuclear Factor-ĸB and Its Related Inflammatory Mediators

Meng

Duan²,

Zhang³

et al. 2011

Respiration

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Background: Few data are available on the role of neutrophil elastase (NE) and nuclear factor-ĸB (NF-ĸB) in the course of seawater drowning-induced acute lung injury (SWD-ALI), and there is no evidence on the value of giving urinary trypsin inhibitor (UTI) in the case of SWD-ALI. Objective: To investigate the role of NF-ĸB and NE in the pathogenesis of SWD-ALI and whether UTI treatment can attenuate SWD-ALI in rabbits. Methods: Rabbits were randomly assigned to control, seawater drowning, and UTI treatment groups. The rabbits in the control group only suffered from intubation, whereas the rabbits in the seawater drowning group and the UTI treatment group received arterial injection of normal saline without/with 50,000 U/kg body weight of UTI after instillation of seawater into an endotracheal catheter. The activities or contents of NF-ĸB, MPO, NE, TNF-α, and IL-10 in lung tissue were measured by nonradioactive EMSA, biochemical methods, and ELISA, respectively. Results: After the seawater challenge, all of the rabbits demonstrated immediate drops in arterial PaO₂/FiO₂ and pronounced pulmonary edema and inflammatory cell infiltration with evidence of an increase in the ratio of wet weight to dry weight, lung permeability index, lung injury scores, and the activities or contents of NF-ĸB, NE, MPO, TNF-α, and IL-10. UTI treatment markedly attenuated lung histopathological changes with evidence of a decrease in all of the parameters, except for upregulation of IL-10. Arterial PaO₂/FiO₂ was significantly improved after 6 h of UTI treatment. Conclusion: These results suggest that NF-ĸB and NE play an important role in SWD-ALI. UTI protects against SWD-ALI, at least partly, through inhibition of the enhanced local activity of NF-ĸB, contents of TNF-α and NE, and infiltration of neutrophils and promotion of the level of IL-10.

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Section: Animals and Methodsmentioning

confidence: 99%

“…Exposure of the lower respiratory tract to seawater can simulate ALI induced by seawater drowning (SWD-ALI) [2]. Seawater-related respiratory involvement can result from seawater-induced oxidant stress and tissue injury and/or from the local upregulation of inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

Urinary Trypsin Inhibitor Attenuates Seawater-Induced Acute Lung Injury by Influencing the Activities of Nuclear Factor-ĸB and Its Related Inflammatory Mediators

Meng

Duan²,

Zhang³

et al. 2011

Respiration

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“…Although the exact therapeutic role of steroids in pulmonary oedema is not yet clear, it is well documented that steroids significantly activate expression of a-ENaC [13,31,32]. a-ENaC, in addition to other therapeutic benefits that steroids may have, might promote clearance of lung oedema fluid, and its benefit in ALI has been shown in animal studies [33,34]. Compared with nonsmokers, smokers are generally less responsive to steroid treatment [18].…”

Section: Cigarette Smoke Inhibitsmentioning

confidence: 99%

Cigarette smoke condensate inhibits ENaC α-subunit expression in lung epithelial cells

Ferro²,

Chu³

2007

Eur Respir J

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Cigarette smoke has been associated with lung fluid accumulation and increased risk of acute respiratory distress syndrome. It was postulated that ENaC a-subunit, which plays a critical role in lung fluid absorption, is affected by cigarette smoke.Cigarette smoke condensate (CSC) was used to treat a human lung epithelial cell line. ENaC a-subunit expression was measured using immunoblotting, quantitative PCR and promoterreporter assays.The current authors found that CSC, without affecting cell survival, suppressed a-subunit expression at the transcriptional level in a dose-and time-dependent fashion. This suppression is neither related to nicotine nor due to an increase of hydrogen peroxide levels in CSC-treated cells. CSC also suppressed a-subunit core promoter activity. Dexamethasone, which activates the core promoter, was able to attenuate the inhibitory effect of CSC. However, in the presence of CSC, dexamethasone was unable to elicit a full-scale activation of a-subunit expression. This inhibition of dexamethasone was partially reversed by withdrawal of CSC.The present results demonstrate that cigarette smoke condensate inhibits ENaC a-subunit expression at the transcriptional level through its promoter. This inhibition could be reversed by dexamethasone. The results also suggest that higher doses of dexamethasone may be needed to activate a-subunit expression in smokers' lungs compared with nonsmokers' lungs, and that quitting smoking might improve the effectiveness of dexamethasone.

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“…In seawater aspiration-induced ALI animal models, the inflammatory cells which have infiltrated into alveolar spaces release several molecules, such as pro-inflammatory cytokines, reactive oxygen species, contributing to the pulmonary inflammatory process. In addition, lung edema is prominent in seawater induced ALI because high osmotic seawater pull water through vascular endothelial cells and alveolar epithelial cells [4], [5]. It has been reported that increased alveolar epithelial and pulmonary microvascular endothelial permeability trigger the transmigration of inflammatory cells such as neutrophils and the formation of edema fluid [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, whether calcitriol can inhibit inflammation and lung epithelial-endothelial barrier permeability in seawater aspiration-induced ALI remains unclear. Corticoids is a drug option in the clinical therapy of ALI/ARDS and dexamethasone treatment has been proved to have therapeutic effects in seawater aspiration-induced ALI [4]. Therefore, we choose dexamethasone as a positive control drug.…”

Section: Introductionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Ameliorates Seawater Aspiration-Induced Acute Lung Injury via NF-κB and RhoA/Rho Kinase Pathways

et al. 2014

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IntroductionInflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses inflammation, it has not been confirmed to be effective in seawater aspiration-induced ALI. Thus, we investigated the effect of calcitriol on seawater aspiration-induced ALI and explored the probable mechanism.MethodsMale SD rats receiving different doses of calcitriol or not, underwent seawater instillation. Then lung samples were collected at 4 h for analysis. In addition, A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not and then stimulated with 25% seawater for 40 min. After these treatments, cells samples were collected for analysis.ResultsResults from real-time PCR showed that seawater stimulation up-regulated the expression of vitamin D receptor in lung tissues, A549 cells and RPMVECs. Seawater stimulation also activates NF-κB and RhoA/Rho kinase pathways. However, we found that pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways. Meanwhile, treatment of calcitriol also improved lung histopathologic changes, reduced inflammation, lung edema and vascular leakage.ConclusionsThese results demonstrated that NF-κB and RhoA/Rho kinase pathways are critical in the development of lung inflammation and pulmonary edema and that treatment with calcitriol could ameliorate seawater aspiration-induced ALI, which was probably through the inhibition of NF-κB and RhoA/Rho kinase pathways.

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Dexamethasone treatment attenuates early seawater instillation-induced acute lung injury in rabbits

Cited by 38 publications

References 34 publications

Urinary Trypsin Inhibitor Attenuates Seawater-Induced Acute Lung Injury by Influencing the Activities of Nuclear Factor-ĸB and Its Related Inflammatory Mediators

Urinary Trypsin Inhibitor Attenuates Seawater-Induced Acute Lung Injury by Influencing the Activities of Nuclear Factor-ĸB and Its Related Inflammatory Mediators

Cigarette smoke condensate inhibits ENaC α-subunit expression in lung epithelial cells

1α,25-Dihydroxyvitamin D3 Ameliorates Seawater Aspiration-Induced Acute Lung Injury via NF-κB and RhoA/Rho Kinase Pathways

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