Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats

Abstract

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.

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

“…Taking into account all of the above, Cu-AOs should play a significant role in the development of BA, since they catalyze the formation of three dangerous products during the reaction of oxidative deamination of biogenic amines: ROS, reactive aldehydes (or reactive carbonyl species, RCS), and ammonia, which is a precursor in the synthesis of RNS [11]. Thus, the aim of this work was to prove the correctness of our assumption about the participation of Cu-AOs in the development of BA features by using the ovalbumin(OVA)-induced model of BA in guinea pigs and semicarbazide (SC), an irreversible inhibitor of these enzymes [12].…”

“…All further steps were carried out at 0-4°C. Frozen guinea pig lungs were used to prepare samples for LOX activity as described previously [12].…”

“…AOs activities. Determination of AOs activities (SSAO, DAO, and LOX) was carried out by the fluorometric method according to [12].…”