Effects of hydrocortisone on activation of inflammation via interleukin-33 in ventilator-induced lung injury.

Despite mechanical ventilation being a very important life-saving intervention, ventilator-induced lung injury (VILI) is related with inflammatory effects and causes high mortality. Our previous study demonstrated that the interleukin-33 (IL-33) cytokine pathway is a biomarker of VILI. The purpose of this study was to further explore the effects of hydrocortisone sodium succinate (HC) on pro-inflammatory IL-33 activation by VILI. The rats were intubated and received ventilation at 20 cmH2O of inspiratory pressure (PC20) by a G5 ventilator for 4 h as a control group, and an intervention group received the same inspiratory pressure as well as treated with HC at 1 mg/kg at the third hour of ventilation (PC20+HC). The hemodynamic and respiratory data showed similar changes in the two groups that were exposed to VILI. The pathophysiological results showed that the HC treatment attenuated the VILI severity. Treatment of HC increased IL-33 expression in the bronchoalveolar lavage fluid (BALF). These results demonstrated that IL-33 is involved in VILI processing and HC treatment attenuated IL-33 involvement in inflammatory activation in VILI. In conclusion, IL-33 may play an important role in VILI.

Membrane translocation of IL-33 receptor in ventilator induced lung injury.

Ventilator-induced lung injury is associated with inflammatory mechanism and causes high mortality. The objective of this study was to discover the role of IL-33 and its ST2 receptor in acute lung injury induced by mechanical ventilator (ventilator-induced lung injury; VILI). Male Wistar rats were intubated after tracheostomy and received ventilation at 10 cm H2O of inspiratory pressure (PC10) by a G5 ventilator for 4 hours. The hemodynamic and respiratory parameters were collected and analyzed. The morphological changes of lung injury were also assessed by histological H&E stain. The dynamic changes of lung injury markers such as TNF-α and IL-1ß were measured in serum, bronchoalveolar lavage fluid (BALF), and lung tissue homogenization by ELISA assay. During VILI, the IL-33 profile change was detected in BALF, peripheral serum, and lung tissue by ELISA analysis. The Il-33 and ST2 expression were analyzed by immunohistochemistry staining and western blot analysis. The consequence of VILI by H&E stain showed inducing lung congestion and increasing the expression of pro-inflammatory cytokines such as TNF-α and IL-1ß in the lung tissue homogenization, serum, and BALF, respectively. In addition, rats with VILI also exhibited high expression of IL-33 in lung tissues. Interestingly, the data showed that ST2L (membrane form) was highly accumulated in the membrane fraction of lung tissue in the PC10 group, but the ST2L in cytosol was dramatically decreased in the PC10 group. Conversely, the sST2 (soluble form) was slightly decreased both in the membrane and cytosol fractions in the PC10 group compared to the control group. In conclusion, these results demonstrated that ST2L translocation from the cytosol to the cell membranes of lung tissue and the down-expression of sST2 in both fractions can function as new biomarkers of VILI. Moreover, IL-33/ST2 signaling activated by mechanically responsive lung injury may potentially serve as a new therapy target.

Hepatoprotective and anti-oxidant activities of Glossogyne tenuifolia against acetaminophen-induced hepatotoxicity in mice.

The present study investigated the anti-oxidative and hepatoprotective effects of Glossogyne tenuifolia (GT) Cassini, against acetaminophen-induced acute liver injury in BALB/c mice. The extracts of GT by various solvents (hot water, 50% ethanol and 95% ethanol) were compared for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, total phenolic content, and total anti-oxidant capacity. The results showed that hot water (HW) extracts of GT contained high levels of phenolics and exerted an excellent anti-oxidative capacity; thus, these were used in the animal experiment. The male BALB/c mice were randomly divided into control group, acetaminophen (APAP) group, positive control group and two GT groups at low (GT-L) and high (GT-H) dosages. The results showed that mice treated with GT had significantly decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). GT-H increased glutathione levels and the ratios of reduced glutathione and oxidized glutathione (GSH/GSSG) in the liver, and inhibited serum and lipid peroxidation. This experiment was the first to determine phenolic compounds, chlorogenic acid and luteolin-7-glucoside in HW extract of GT. In conclusion, HW extract of GT may have potential anti-oxidant capacity and show hepatoprotective capacities in APAP-induced liver damaged mice.