Nitazoxanide ameliorates OVA-induced airway inflammation in asthmatic mice via p38-MAPK/NFkB and AMPK/STAT3 pathways

Abstract

AbstractNitazoxanide has an anti-inflammatory effect, we clarified the ameliorative effect of nitazoxanide on asthmatic airway inflammation by conducting in vitro and in vivo experiments. In vitro, we assessed the effect of nitazoxanide on cytokine production by lipopolysaccharide-stimulated RAW 264.7 cells, as well as the diastolic effect of nitazoxanide on isolated rat airways. Nitazoxanide was found to have a diastolic effect on isolated tracheal spasms caused by spasmogenic substances, and to inhibit IL-6 and IL-1β production by RAW 264.7 cells. Meanwhile, nitazoxanide can inhibit the proliferation and migration of human bronchial smooth muscle cells (HBSMCs). In vivo, an ovalbumin (OVA)-induced asthma model was established in mice, and the airway resistance was measured by Whole Body Plethysmography (WBP) after inhalation of acetylcholine in mice, and the levels of IL-4, IL-6, IL-12, and IL-17 were detected in bronchoalveolar lavage fluid (BALF) of mice by ELISA and the inflammatory cells were counted. H&E staining was used to observe the changes in lung histopathology, and the expression of NFkB, MAPK, AMPK, and STAT3 in lung tissues was quantified using Western-blot. Nitazoxanide reduced inflammatory cell infiltration and goblet cell proliferation in the lungs of asthmatic mice. Moreover, the expression of IL-4, IL-5, and IL-6 in BALF was down-regulated in asthmatic mice. In addition, nitazoxanide could inhibit the expression of NFkB, MAPK, STAT 3 proteins and ascend the expression of AMPK in lung tissues. In conclusion, nitazoxanide could diastole airway smooth muscle and ameliorate OVA-induced airway inflammation in asthmatic mice via NFkB/MAPK and AMPK/STAT3 pathways.