The NADPH oxidase NOX2 mediates isoflurane-induced lung cell injury in vitro and in vivo.

Background: Isoflurane is a widely used inhaled anesthetic, but its administration has been linked to increased reactive oxygen species (ROS) and pro-inflammatory cytokines. NADPH oxidases are suggested as the primary ROS source. This study aimed to evaluate the mechanisms by which isoflurane induces ROS and reactive nitrogen species (RNS) in vitro in human and murine cells and in vivo using wild-type (WT) and NOX2 knockout (NOX2^-/-) mice.

Methods: J774A.1 macrophages and MRC-5 fibroblast were exposed to 2 % isoflurane or ambient air for 3 or 6 h. In vivo, 28 mice (WT and NOX2^-/-) were divided into four groups (n = 7/group) and exposed to 2 % isoflurane for 3 h.

Results: Isoflurane significantly altered cell metabolism and increased ROS production. In vivo, ISOWT (12.42 ± 4.44); (10.19 ± 3.44) mice showed greater leukocyte and macrophage influx in bronchoalveolar lavage fluid (BALF) than WT controls (p < 0.05). Superoxide dismutase, catalase activity, and the expression of iNOS, IL-1β, NF-κB, and Nrf2 were significantly elevated in ISOWT mice compared to the control (p < 0.0411). Levels of CCL2, IL-1β, and IL-6 also increased in ISOWT compared to WT (p < 0.0391). However, no significant differences were found between NOX2^-/-isoflurane-exposed mice and their controls.

Conclusion: These findings demonstrate that the NADPH oxidase NOX2 plays a key role in oxidative stress and inflammation in the lungs of healthy mice exposed to isoflurane.