Inflammation is the body’s response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release inflammatory mediators such as pro-inflammatory cytokines, lipids and reactive oxygen species (ROS). Lung epithelial cells and phagocytes (monocytes, macrophages and neutrophils) produce ROS mainly by the NADPH oxidase NOX1 and NOX2, respectively. The aim of this study was to investigate the effects of two NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI), on lipopolysaccharide (LPS)-induced lung inflammation in rats. Our results showed that apocynin and DPI attenuated the LPS-induced morphological and histological alterations of the lung, reduced edema and decreased lung permeability. The evaluation of oxidative stress markers in lung homogenates showed that apocynin and DPI inhibited LPS-induced NADPH oxidase activity, and restored superoxide dismutase (SOD) and catalase activity in the lung resulting in the reduction in LPS-induced protein and lipid oxidation. Additionally, apocynin and DPI decreased LPS-induced MPO activity in bronchoalveolar liquid and lung homogenates, TNF-α and IL-1β in rat plasma. NADPH oxidase inhibition could be a new therapeutic strategy for the treatment of inflammatory lung diseases.

The peptidyl-prolyl cis/trans-isomerase, NIMA-interacting 1 (Pin1), is involved in several cellular functions by changing the conformation and activity of phosphorylated proteins. Its key role in cellular signalling makes Pin1 an appealing target for the development of pharmacological agents to treat diseases such as inflammation. Pulmonary inflammation is a major disease resulting from the activation of immune cells by microbes or pollutants. In this study, we examined the effects of two Pin1 inhibitors, PiB and juglone, on lipopolysaccharide (LPS)-induced pulmonary inflammation in rats. Our results demonstrate that the intraperitoneal (i.p.) administration of 3 mg/kg of PiB and juglone mitigates LPS-induced pulmonary inflammation by reducing haemorrhage, vascular injury, pulmonary oedema and immune cell accumulation in the airway region. Furthermore, these Pin1 inhibitors were found to protect rats against the overproduction of inflammatory markers by inhibiting myeloperoxidase (MPO) and lactate dehydrogenase (LDH) activities, as well as reducing plasma C-reactive protein (C-RP). Additionally, PiB and juglone protected the rats from nitric oxide synthase (NOS) hyperactivity, preventing oxidative stress by decreasing pro-oxidant markers and restoring the antioxidant enzymes such as catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). The use of juglone and PiB could therefore be an effective means of alleviating acute respiratory inflammation by modulating inflammatory and oxidant pathways and preserving lung microstructure.