Involvement of Cu-containing amine oxidases in the development of lung pathology in ovalbumin-induced bronchial asthma in guinea pigs

Abstract

Bronchial asthma is developed as an immune response to allergen challenges accompanied by inflammation and fibrosis implicated in airway remodeling. To reveal the causative implication of Cu-containing amino oxidases semicarbazide-sensitive amine oxidase (SSAO), DAO and lysyl oxidase (LOX) in BA development we used their irreversible inhibitor semicarbazide and guinea pig model of BA induced by ovalbumin. Semicarbazide was introduced to asthmatic animals via drink or inhalation. At the 16th week after disease induction, the increase in the activity of pro-inflammatory SSAO and DAO in plasma (1.6 and 2 times, respectively) was observed. The introduction of semicarbazide to asthmatic animals via drink or inhalation significantly decreased activities of these enzymes compared to the untreated asthmatic animals. A considerable­ increase in IL-13 content and LOX activity in the lung tissue of asthmatic animals were observed that evidenced airway inflammation and pulmonary fibrosis development. The uptake of semicarbazide by guinea pigs with bronchial asthma led to normalization of LOX activity. Histological studies confirmed that semicarbazide attenuated morphopathological changes in the lungs of asthmatic animals. Thus, the data obtained indicate the direct participation of the studied enzymes in the progression of pathological processes in atopic bronchial asthma as well as the potential use of semicarbazide as a drug in complex anti-asthmatic therapy. Keywords: atopic bronchial asthma, histaminase/diamine oxidase, IL-13, lysyl oxidase, nitric oxide, semicarbazide, semicarbazide sensitive amine oxidase