The pathogenesis of pulmonary fibrosis (PF) is accompanied by extracellular matrix (ECM) deposition, oxidative stress, and inflammation progression, as well as hyperactivation of amine oxidases (AOs), which contribute to disease manifestation. The present study aims to elucidate the effect of semicarbazide (SC), an inhibitor of Cu-containing AOs: lysyl oxidase (LOX), semicarbazide sensitive amine oxidase (SSAO), diamine oxidase (DAO), on PF induced in rats by bleomycin (BLM). Eighteen male Wistar rats were randomly divided into four groups: Control, rats of BLM group received BLM (5 mg/kg, intratracheally once), BLM+SC group obtained 0.005% solution of SC (about 50 µg per capita per day) for three weeks starting immediately after BLM injection, and the Control+SC group drank the same solution as BLM+SC group. The content of cross-linked collagen in total bronchi and free radicals in lung, activities of LOX, SSAO, DAO, polyamine oxidase (PAO), Cu, Zn-superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPx) in lung and blood were measured. BLM injection induced PF that was confirmed histologically and morphometrically as well as by the elevation of the content of cross-linked collagen and free radicals. The activities of LOX and SSAO involved in post-translational modification of ECM and inflammation were significantly increased (P < 0.05). The activities of DAO, and PAO that control polyamine metabolism were also essentially raised. Among antioxidant enzymes, only GPx was activated in the BLM group as compared to control. These changes were absent in the BLM+SC group. SC intake promoted the fact that the histology and morphometric parameters of lung tissue, the content of cross-linked collagen in the bronchi and free radicals in the lung, as well as the activity of the studied enzymes remained at the control level. Our data suggest that SC suppresses the development of BLM-induced PF by inhibiting AOs activities. K e y w o r d s: pulmonary fibrosis, bleomycin, amine oxidases, redox state, antioxidant enzymes, semicarbazide.

amine oxidases are involved in the progression of many diseases and their complications, including renal failure, due to the generation of the three toxic metabolites (H 2 O 2 , aldehydes, and ammonia) in the course of biogenic amines oxidative deamination. The participation of the first two products in kidney pathogenesis was confirmed, whereas the role of ammonia as a potential inducer of the nitrozative stress is not yet understood. The aim of the present study was to test how further intensification of oxidative stress would affect diabetes-mediated metabolic changes. For this purpose, a rat model of glycerol-induced rhabdomyolysis, as a source of powerful oxidative stress due to the release of labile Fe 3+ from ruptured myocytes, on the background of streptozotocin-induced diabetes was used. The experimental animal groups were as follows: group 1 -'Control', group 2 -'diabetes', group 3 -'diabetes + rhabdomyolysis'. a multifold increase in semicarbazide sensitive amine oxidase (SSAO) activity in the kidney and blood, free radicals (FR), MetHb and 3-nitrotyrosine (3-NT) levels in the blood, as well as the emergence of HbNO in plasma and dinitrosyl iron complexes (DNICs) in the liver of animals in group 2 as compared to control were revealed. An additional increase in FR, HbNO levels in the blood, and DNICs in the liver of animals in the diabetes + rhabdomyolysis group as compared to the diabetes group, which correlated with the appearance of a large amount of Fe 3+ in the blood of group 3 animals, was detected. Unexpectedly, we observed the positive regulatory effects in animals of the diabetes + rhabdomyolysis group, in particular, a decreased SSaO activity in the kidney and 3-NT level in plasma, as well as the normalization of activity of pro-and antioxidant enzymes in the blood and liver compared to animals of diabetes group. these consequences mediated by rhabdomyolysis may be the result of NO exclusion from the circulation due to the excessive formation of NO stable complexes in the blood and liver. The data obtained allow us to consider SSAO activity as a marker of renal failure in diabetes mellitus. In addition, we suggest a significant role of nitrosative stress in the development of pathology, and, therefore, recommend NO-traps in the complex treatment of diabetic complications.

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