Mechanical ventilation with high tidal volume increased the generation of reactive oxygen stress (ROS), cytokine responses, and the activation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-jB associated with lung injury [71] . In an isolated, perfused rat model, the administration of apocynin, a strong oxidative inhibitor known to block nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in neutrophils, macrophages, and endothelium [72] [73] [74] , depressed oxidative stress, attenuated inflammatory responses, and reduced ventilatorinduced lung injury (VILI) [71] .