EFFECT OF THE NADPH OXIDASE INHIBITOR APOCYNIN ON SEPTIC LUNG INJURY IN GUINEA-PIGS

Reactive oxygen species (ROS) produced by NADPH oxidase activation in neutrophils play a major role in mediating sepsis-induced acute lung i njury. To provide insight into whether the NADPH oxidase inhibitor apo cynin might attenuate oxidant-induced lung injury, we examined the eff ect of apocynin on (1) sepsis-induced lung injury in guinea pigs, (2) ROS generation by LPS-stimulated neutrophils measured by chemiluminesc ence (CL), and (3) LPS-stimulated neutrophil-mediated human umbilical vein endothelial cell (HUVEC) injury assessed by Cr-51 release. Sepsis -induced lung injury in guinea pigs was assessed by comparing I-125-la beled albumin concentrations in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (UP and BAL/P), lung wet-to-dry weight ratios, and the number of neutrophils in BAL fluid. The lung wet-to-d ry weight ratio, L/P, and the number of neutrophils in BAL fluid decre ased after pretreatment and post-treatment with apocynin. BAL/P decrea sed upon pretreatment but not upon post-treatment with apocynin. Apocy nin at concentrations from 10 to 100 mu g/ml significantly reduced LPS -stimulated neutrophil CL and neutrophil-mediated HUVEC Cr-51 release. We conclude that the NADPH oxidase inhibitor apocynin attenuates (1) sepsis-induced lung injury in guinea pigs, (2) neutrophil ROS generati on measured by CL, and (3) neutrophil-mediated HUVEC injury assessed b y Cr-51 release.