Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Abstract

Background: Mechanical ventilation has been documented to paradoxically cause lung injury. As a commonly used volatile anesthetic, sevoflurane has been proven to possess antiinflammatory and antioxidative properties. This study aims to investigate the protective effects of sevoflurane on inflammation and ventilator-induced lung injury during mechanical ventilation in healthy mice. Methods: The adult healthy mice were divided into four groups, each consisting of ten subjects: mice in group Con-L VT and group Sev-L VT were ventilated with tidal volumes of 8 mL/kg for 4 hours, while those in group Con-H VT and group Sev-H VT were ventilated with tidal volumes of 16 mL/kg instead. Control mice (group Con-L VT and Con-H VT ) were subjected to fresh air, while sevoflurane-treated mice (groups Sev-L VT and Sev-H VT ) were subjected to air mixed with 1 vol% sevoflurane. After 4 hours of ventilation, the bronchoalveolar lavage (BAL) fluid was collected and analyzed for the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10. Lung homogenates were harvested to detect the expression of nuclear factorkappa B (NF-κB) and heme oxygenase (HO)-1 mRNA by reverse transcription-polymerase chain reaction method. Lung damage was evaluated using the modified Ventilator-Induced Lung Injury histological scoring system. Results: Compared to group Con-L VT , the levels of TNF-α, IL-1β, IL-6, and IL-10 in BAL fluid, mRNA expressions of NF-κB and HO-1 in lung tissue, and lung injury scores were significantly increased in group Con-H VT ; compared to group Con-H VT , group Sev-H VT BAL samples showed decreased levels of TNF-α, IL-1β, and IL-6; they also showed increased levels of IL-10, the downregulation of NF-κB mRNA, and HO-1 mRNA upregulation; the lung injury scores were significantly lower in group Sev-H VT than group Con-H VT . Conclusion: Mechanical ventilation with high tidal volume might lead to lung injury, which could be significantly, but not completely, attenuated by sevoflurane inhalation by inhibiting the NF-κB-mediated proinflammatory cytokine generation and upregulating HO-1 expression.

Improvement of ventilation-induced lung injury in a rodent model by inhibition of inhibitory κB kinase

“…26 Our results showed that the IL-10 production was increased in the HVT + vehicle group; this effect may be an endogenous protective mechanism. 22 The IKK 16 administration further elevated IL-10 levels, and this was accompanied by a decreased IL-6 concentration. It is suggested that a reduced IL-10 production is thought to be mediated via the activation of IL-6 suppressor of cytokine signaling 3 signaling pathway in a fetal Type II epithelial cell exposed to mechanical stretch.…”

“…2 An administration of drugs with anti-inflammatory features has shown a decrease in VILI. 3,22 Lung inflammation triggered by excessive lung stretch in VILI is thought to be partially modulated by autophagy, an intracellular proteolytic system, via the activation of the NF-JB pathway. 8 NF-JB is an essential transcription factor that regulates the gene expression of various proinflammatory mediators, such as TNF-> and IL-6, which have been shown to play a key role in neutrophil activation and migration into the lung.…”

Sevoflurane preconditioning protects from posttransplant injury in mouse lung transplantation

“…3 PGD and AR are not only responsible for early transplant morbidity and mortality, 4 but these two pathologic entities predominantly contribute to the development of chronic lung allograft dysfunction, the major impediment to long-term survival of lung transplanted patients. 5 Preconditioning by sevoflurane (Sevo), a clinically frequently used volatile anesthetic, has been shown to attenuate ischemiaereperfusion (I/R) injury and also AR in several organs, such as liver, kidney, heart, and lung [6][7][8][9] through reducing inflammatory cytokines, 10,11 chemokines, 12 and adhesion molecules. 13 A possible mechanism responsible for this beneficial effect has been attributed to the homeostasis of adenosine triphosphate in mitochondria with slower calcium influx 14 and antioxidant activity.…”

Alveolar formation is dysregulated by restricted nutrition but not excess sedation in preterm lambs managed by noninvasive support

“…Postnatal sedation may reduce postnatal nutrition and growth via effects on gastrointestinal motility, absorption, and blood flow (18–21). In the developing lung, sedation may also directly affect alveolar formation by disruption of lung cell-signaling pathways (22–24). …”