Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies

Luh, Shi‐Ping; Chiang, Chiao–Hsi

doi:10.1631/jzus.2007.b0060

Cited by 80 publications

(61 citation statements)

References 97 publications

(82 reference statements)

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“…1,2 Since the first description of ALI/ARDS, in 1967, numerous studies have been conducted to better understand the pathogenesis. 3,4 Exposure to hazardous factors such as acid, lipopolysaccharide, hyperoxia, or overinflation generates excessive levels of reactive oxygen species (ROS) and recruitment of considerable amounts of neutrophils in lung tissue, thus resulting in proinflammatory processes and eventually cellular, and tissue dysfunction, which contributes to increased vascular permeability, leukocyte infiltration, plasma exudation and impaired arterial oxygenation.…”

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confidence: 99%

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Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Chen

Zheng

Liu

et al. 2015

Laboratory Investigation

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The role of endogenous sulfur dioxide (SO 2 ), an efficient gasotransmitter maintaining homeostasis, in the development of acute lung injury (ALI) remains unidentified. We aimed to investigate the role of endogenous SO 2 in the pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established. Endogenous SO 2 levels, lung injury, oxidative stress markers and apoptosis were examined. OA-induced ALI rats showed a markedly downregulated endogenous SO 2 /aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury. Chemical colorimetry assays demonstrated upregulated reactive oxygen species generation and downregulated antioxidant capacity in OA-induced ALI rats. However, SO 2 increased endogenous SO 2 levels, protected against oxidative stress and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar epithelial cells SO 2 downregulated O 2 À and OH À generation. In contrast, L-aspartic acid-b-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of endogenous SO 2 generating enzyme, promoted free radical generation, upregulated poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted cell apoptosis. Importantly, apoptosis could be inhibited by the free radical scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest that SO 2 /AAT1/AAT2 pathway might protect against the development of OA-induced ALI by inhibiting oxidative stress.

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confidence: 99%

“…1 Steroids are sometimes used in the treatment of ALI for its major effect of anti-inflammation, improving the lung injury. 55 However, the use of steroids is clinically controversial due to its side effects, eg, infection, etc.…”

mentioning

confidence: 99%

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Chen

Zheng

Liu

et al. 2015

Laboratory Investigation

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“…Acute lung injury (ALI) is characterized by damage to the alveolar epithelial and capillary endothelial cells (1). ALI can be induced by various factors, such as pulmonary alveolar hemorrhage, shock and transfusion, resulting in diffuse pulmonary interstitial and alveolar edema, refractory hypoxemia and respiratory distress (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Penehyclidine ameliorates acute lung injury by inhibiting Toll-like receptor 2/4 expression and nuclear factor-κB activation

Wang

Che

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the effect of penehyclidine (PHC) on endotoxin-induced acute lung injury (ALI), as well as to examine the mechanism underlying this effect. A total of 60 rats were randomly divided into five groups, including the control (saline), LPS and three LPS + PHC groups. ALI was induced in the rats by injection of 8 mg lipopolysaccharide (LPS)/kg body weight. The rats were then treated with or without PHC at 0.3, 1 or 3 mg/kg body weight 1 min following LPS injection. After 6 h, serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were determined by ELISA. In addition, the mRNA expression levels of toll-like receptor (TLR)2 and TLR4 were examined by reverse transcription-quantitative polymerase chain reaction in the lung tissue samples, and nuclear factor (NF)-κB p65 protein expression levels were examined by western blot analysis. The results demonstrated that lung injury was ameliorated by treatment with PHC (1 and 3 mg/kg body weight) as compared with treatment with LPS alone. Injection of LPS significantly increased the mRNA expression levels of TLR2 and TLR4, as well as the protein expression levels of NF-κB p65 in the lung tissue samples. Serum levels of TNF-α and IL-6 were also upregulated by LPS injection. Treatment of the rats with PHC following LPS injection suppressed the LPS-induced increase in TLR2/4 mRNA and NF-κB p65 protein expression levels. PHC also inhibited the increase in TNF-α and IL-6 serum levels. In addition, PHC reduced LPS-induced ALI and decreased the serum levels of TNF-α and IL-6, possibly by downregulating TLR2/4 mRNA expression and inhibiting NF-κB activity, and consequently alleviating the inflammatory response.

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“…A SDRA, embora possa ter início agudamente, pode persistir por dias e até semanas BHATIA e MOOCHHALA, 2004;LUH et al, 2007). O pulmão acometido por inflamação apresenta infiltrado neutrofílico, aumento da permeabilidade vascular, danos à barreira do epitélio alveolar e comprometimento das trocas gasosas.…”

Section: Discussionunclassified

“…O pulmão acometido por inflamação apresenta infiltrado neutrofílico, aumento da permeabilidade vascular, danos à barreira do epitélio alveolar e comprometimento das trocas gasosas. Por causa disso, dois aspectos acerca da SDRA tornam seu estudo relevante: a falta de terapia medicamentosa eficaz e a alta taxa de mortalidade (LUH et al, 2007;LEWANDOWSKI e LEWANDOWSKI, 2006). Além disso, baseados em estudos do nosso laboratório (CAVRIANI et al, 2005;CAVRIANI et al, 2007;COELHO et al, 2007;BREITHAUPT-FALOPPA et al, 2009) e naqueles descritos para eventos traumáticos associados ao choque hemorrágico (DEITCH et al, 2001;DAVIDSON et al, 2004), lançamos a hipótese de que o intestino, sob sofrimento isquêmico, pode ser considerado um potente gerador de mediadores inflamatórios, os quais, uma vez drenados pelo sistema linfático, atingem a circulação pulmonar, comprometem a sua homeostasia, causam recrutamento de neutrófilos, edema, contribuindo para a lesão tecidual e para a disfunção pulmonar frequentemente observada na SDRA.…”

Section: Discussionunclassified

Perfil temporal da inflamação pulmonar induzida pela isquemia/reperfusão intestinal em ratos. Estudo do papel do sistema linfático.

Vitoretti¹

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AgradecimentosEstudos clínicos e experimentais relatam a que a isquemia e reperfusão (I/R) intestinal induz lesão pulmonar aguda (LPA), que em casos mais graves evolui para a síndrome do desconforto respiratório agudo (SDRA). A LPA se caracteriza pela liberação de um amplo espectro de mediadores inflamatórios, infiltração de neutrófilos e aumento de permeabilidade vascular. Sabe-se que mediadores inflamatórios gerados no local da I/R intestinal são transportados pelo sistema linfático mesentérico e, ao atingirem o pulmão, contribuem para a LPA. Por outro lado, dados sobre os efeitos tardios da I/R intestinal e do papel do sistema linfático na LPA ainda são fragmentados. No presente estudo ratos machos Wistar anestesiados foram submetidos a 45 min de isquemia intestinal pela obstrução da artéria mesentérica superior e a 24 h, 72 h ou 120 h de reperfusão. Estudos onde o ducto linfático torácico superior foi bloqueado antes da I/R intestinal também foram conduzidos. Decorrido o tempo desejado de reperfusão intestinal quantificamos a atividade de mieloperoxidase (MPO), o extravasamento do corante azul de Evans (AE), mediadores inflamatórios na linfa e em explante de pulmão. Foram também quantificadas a expressão de moléculas de adesão e o efeito do tratamento dos animais com antibiótico de amplo espectro. A I/R intestinal causou aumento de atividade da MPO e de AE extravasado no pulmão 120 h após a reperfusão intestinal sendo que o bloqueio do fluxo linfático atenuou o AE extravasado. A linfa dos animais I/R intestinal revelou níveis elevados de IL-1, IL-6, VEGF e LTB 4 . No explante de pulmão detectamos aumento da concentração de VEGF e de IL-1e redução de IL-10 120 h após a reperfusão intestinal com o ducto linfático intacto ou bloqueado em relação aos outros períodos estudados. A I/R intestinal de 120 h aumentou o número de monócitos, de plaquetas circulantes e o hematócrito em relação aos demais períodos de reperfusão intestinal. Nossos dados também indicaram diminuição da expressão de vWf e aumento de integrina  1 , PECAM-1 e colágeno tipo I e IV no endotélio pulmonar dos animais 120 h após o início da reperfusão em relação aos demais períodos. O tratamento com antibiótico teve maior ou menor eficácia em reduzir a MPO e o AE extravasado no pulmão, 120h após a reperfusão, dependendo do período da isquemia ou da reperfusão em que o medicamento foi administrado. Concluindo, os dados apresentados indicam que o tempo de reperfusão intestinal medeia a inflamação pulmonar. Mediadores inflamatórios presentes na linfa e na circulação participam do desencadeamento/manutenção da inflamação pulmonar, alterando a integridade do endotélio pulmonar. É possível que a regulação do controle endógeno da inflamação seja alterada de maneira que uma infecção bacteriana possa contribuir para a inflamação pulmonar observada após 120 h de reperfusão intestinal. Experimental and clinical studies have reported that intestinal ischemia/reperfusion (I/R) induces acute lung inflammation (ALI), which can lead, in severe cases, to acute ...

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies

Cited by 80 publications

References 97 publications

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Penehyclidine ameliorates acute lung injury by inhibiting Toll-like receptor 2/4 expression and nuclear factor-κB activation

Perfil temporal da inflamação pulmonar induzida pela isquemia/reperfusão intestinal em ratos. Estudo do papel do sistema linfático.

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