Levobupivacaine attenuates lipopolysaccharide-induced acute lung injury.

Levobupivacaine (LB), a kind of local anesthetic, possesses anti-inflammatory properties. High-mobility group box 1 (HMGB1), a nuclear DNA-binding protein, plays a key role in the development of acute lung injury (ALI). The aim of this study was to investigate whether LB attenuates ALI by the inhibition of HMGB1 expression and to investigate the molecular mechanisms. ALI in male rats was induced by an intratracheal instillation of LPS (5 mg/kg), and male rats received mini-osmotic pumps containing LB 30 min after LPS exposure. A549 alveolar epithelial cells were incubated with LPS in the presence or absence of LB. An enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blotting was used to detect the changes in the expression of toll-like receptor 2/4 (TLR2/4) and the activation of NF-κB. The results showed that LB significantly protected animals from LPS-induced ALI as evidenced by a decrease in the ratio of lung wet to dry weight, total cells, neutrophils, macrophages, and myeloperoxidase activity, associated with a reduced lung histological damage. We also found that LB post-treatment markedly inhibited the release of HMGB1 and other pro-inflammatory cytokines. Furthermore, LB significantly inhibited LPS-induced TLR2/4 protein overexpression and NF-κB activation in the lung tissues and in LPS-stimulated A549 alveolar epithelial cells in vitro. These data indicate that LB attenuated LPS-induced ALI by the inhibition of HMGB1 expression in rats. These benefits were associated with the inhibition of TLR2/4-NF-κB pathway by LB.

Guo D ，Li K ，Yang M ，Zhang H ，Miao Y ... -  《-》

Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells.

Luo Y ，Che W ，Zhao M 《-》

Daidzein attenuates lipopolysaccharide-induced acute lung injury via toll-like receptor 4/NF-kappaB pathway.

Daidzein, a diphenolic isoflavone from many plants and herbs, has been reported to have anti-inflammatory properties. However, the effects of daidzein on lipopolysaccharide (LPS)-induced acute lung injury have not been determined. The aim of this study was to detect the effects of daidzein on LPS-induced acute lung injury and investigate the molecular mechanisms. Daidzein was intraperitoneally injected (2, 4, 8 mg/kg) 30 min after intratracheal instillation of LPS (5 mg/kg) in rats. The results showed that daidzein treatment remarkably improved the pulmonary histology and decreased the lung wet/dry weight ratios. We also found that daidzein significantly inhibited LPS-induced increases of macrophages and neutrophils infiltration of lung tissues, as well as markedly attenuated MPO activity. Moreover, daidzein effectively reduced the inflammatory cytokines release and total protein in bronchoalveolar lavage fluids (BALF). Furthermore, daidzein significantly inhibited LPS-induced toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein up-expressions and NF-κB activation in lung tissues. In vitro, daidzein obviously inhibited the expressions of TLR4 and MyD88 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. In conclusion, these data indicate that the anti-inflammatory effects of daidzein against LPS-induced ALI may be due to its ability to inhibit TLR4-MyD88-NF-κB pathway and daidzein may be a potential therapeutic agent for LPS-induced ALI.

Feng G ，Sun B ，Li TZ 《-》

Ulinastatin Protects Against LPS-Induced Acute Lung Injury By Attenuating TLR4/NF-κB Pathway Activation and Reducing Inflammatory Mediators.

Cao C ，Yin C ，Shou S ，Wang J ，Yu L ，Li X ，Chai Y ... -  《-》

Levobupivacaine inhibits lipopolysaccharide-induced high mobility group box 1 release in vitro and in vivo.

The aim of the study was to investigate whether levobupivacaine (LB) suppressed lipopolysaccharide (LPS)-induced high mobility group box 1 (HMGB1) release in vitro and in vivo, and to determin its molecular mechanisms of action. RAW264.7 cells were treated with LPS and LB for 24 h. Levels of HMGB1, nuclear factor-kappa B (NF-κB) and phosphorylated p38 mitogen-activated protein kinase (MAPK) were measured by Enzyme-linked immunosorbent assay and Western blotting; the levels of HMGB1 messenger RNA were measured by real-time polymerase chain reaction. In addition, cecal ligation and puncture-induced septic C57BL/6 received LB infusion, and the levels of HMGB1 and functional parameters of multiple organs determined using several detection kits. LB inhibited HMGB1 release in vitro and in vivo. Furthermore, LB inhibited the translocation of NF-κB and phosphorylation of p38 MAPK in vitro. Mice treated with LB infusion improved survival in mice and significantly reduced cecal ligation and puncture-induced dysfunction of organs. LB suppresses LPS-induced HMGB1 release in vitro and in vivo by partially inhibiting NF-κB/p38 MAPK pathways. LB can rescue mice from sepsis and protect against organ dysfunction in septic mice.

Ge Y ，Hu S ，Zhang Y ，Wang W ，Xu Q ，Zhou L ，Mao H ... -  《-》