Melatonin attenuates chronic cough mediated by oxidative stress via transient receptor potential melastatin-2 in guinea pigs exposed to particulate matter 2.5.

摘要

The aim of this study was to investigate the effects of melatoninon oxidative stress, the expression of transient receptor potentialmelastatin-2 (TRPM2) in guinea pig brains, and the influence ofmelatonin on oxidative stress in lungs and airway inflammationinduced by particulate matter 2.5 (PM2.5). A particle suspension(0.1 g/ml) was nasally administered to the guinea pigs to preparea PM2.5 exposure model. Cough frequency and cough incubationperiod were determined through RM6240B biological signalcollection and disposal system. Oxidative stress markers,including malondialdehyde (MDA), total antioxidant capacity(T-AOC), total superoxide dismutase (T-SOD), and glutathioneperoxidase (GSH-Px), in the medulla oblongata were examinedthrough spectrophotometer. Reactive oxygen species (ROS) weredetected in the hypoglossal nucleus, cuneate nucleus, Botzingercomplex, dorsal vagal complex, and airway throughdihydroethidium fluorescence. Hematoxylin-eosin (HE) stainingand substance P expression via immunohistochemistry revealedthe inflammatory levels in the airway. TRPM2 was observed inthe medulla oblongata through immunofluorescence and Westernblot. The ultrastructure of the blood-brain barrier and neuronalmitochondria was determined by using a transmission electronmicroscope. Our study suggests that melatonin treatmentdecreased PM2.5-induced oxidative stress level in the brains andlungs and relieved airway inflammation and chronic cough.TRPM2 might participate in oxidative stress in the cough centerby regulating cough.