Apocynin alleviates lung injury by suppressing NLRP3 inflammasome activation and NF-κB signaling in acute pancreatitis

Mounting evidence has demonstrated that acute pancreatitis (AP) is one of the causes of multiple organ damage. NADPH (nicotinamide adenine dinucleotide phosphate) act as a substrate of NADPH oxidase (NOX) to generate reactive oxygen species (ROS), but the role NADPH oxidase signaling pathway plays in AP-induced acute lung injury remains unclear. Apocynin, an inhibitor of NOX, is highly effective in suppressing the production of ROS. Here, we used rat model of severe acute pancreatitis (SAP) to explore whether the NOX inhibitor apocynin produced protective effects in against SAP-induced lung injury via inhibition of inflammation and oxidation. We observed that apocynin significantly attenuated severe acute pancreatitis-induced increase of NOX2, NOX4 and ROS expressions in lung tissues. In addition, the phosphorylation and degradation of I kappa B alpha, and the nuclear localization of NF-kappa B p65 in SAP-induced lung injury were also inhibited after using apocynin. Simultaneously, down-regulation of NOX suppressed the levels of inflammasome proteins including NLRP3, ASC, pro-Caspase-1 and cleaved-Caspase-1 in the lung. Serum levels of TNF-alpha, interleukin (IL)-1 beta and IL-6 were also reduced. Our findings suggest that beyond anti-oxidative effects, apocynin may also have anti-inflammatory effects by suppressing NLRP3 inflammasome activation and NF-kappa B signaling in acute pancreatitis. Therefore, apocynin may have therapeutic potential in the treatment of SAP and SAP-induced lung injury.