Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1

Abstract

Acute respiratory distress syndrome is a life-threatening disease associated with high mortality. The adenosine receptor A2B (Adora2b) provides anti-inflammatory effects, which are also associated with the intracellular enzyme heme oxygenase-1 (HO-1). Our study determined the mechanism of sevoflurane’s protective properties and investigated the link between sevoflurane and the impact of a functional Adora2b via HO-1 modulation during lipopolysaccharide (LPS)-induced lung injury. We examined the LPS-induced infiltration of polymorphonuclear neutrophils (PMNs) into the lung tissue and protein extravasation in wild-type and Adora2b−/− animals. We generated chimeric animals, to identify the impact of sevoflurane on Adora2b of hematopoietic and non-hematopoietic cells. Sevoflurane decreased the LPS-induced PMN-infiltration and diminished the edema formation in wild-type mice. Reduced PMN counts after sevoflurane treatment were detected only in chimeric mice, which expressed Adora2b exclusively on leukocytes. The Adora2b on hematopoietic and non-hematopoietic cells was required to improve the permeability after sevoflurane inhalation. Further, sevoflurane increased the protective effects of HO-1 modulation on PMN migration and microvascular permeability. These protective effects were abrogated by specific HO-1 inhibition. In conclusion, our data revealed new insights into the protective mechanisms of sevoflurane application during acute pulmonary inflammation and the link between sevoflurane and Adora2b, and HO-1 signaling, respectively.

Role of ferroptosis in effects of anesthetics on multiple organ diseases: A literature review

“…HO-1 breaks down heme into nitric oxide, biliverdin, and iron to provide an effective antioxidant defense against cellular stress, which is related to ferroptosis [ 20 ]. Pre-and post-conditioning with sevoflurane might protect against ALI by upregulating HO-1 expression [ 21 , 22 ]. Taken together, these results showed that ferroptosis contributes to the prognosis of ALI, and sevoflurane inhibits ferroptosis by upregulating HO-1 expression to ameliorate LPS-induced ALI, which provides novel insights for the clinical application of sevoflurane in ALI therapy.…”

Pharmacology of Adenosine Receptors: Recent Advancements

“…Sevoflurane reduced LPS-induced polymorphonuclear neutrophil (PMN) infiltration and edema in WT mice. Chimeric mice expressing A 2B ARs exclusively on leukocytes showed decreased PMN counts after sevoflurane treatment [ 158 ]. Recent research demonstrated that A 2B AR activation by adenosine is the mechanism by which cupping, a traditional Chinese alternative therapy, attenuates LPS-induced lung inflammation [ 159 ].…”