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

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 semica...

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Main Authors: O. O. Hudkova, I. P. Krysiuk, T. O. Kishko, N. M. Popova, L. B. Drobot, N. V. Latyshko
Format: Article
Language:English
Published: National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 2021-10-01
Series:The Ukrainian Biochemical Journal
Subjects:
Online Access:http://ukrbiochemjournal.org/wp-content/uploads/2021/10/Hudkova_5_21.pdf
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author O. O. Hudkova
I. P. Krysiuk
T. O. Kishko
N. M. Popova
L. B. Drobot
N. V. Latyshko
author_facet O. O. Hudkova
I. P. Krysiuk
T. O. Kishko
N. M. Popova
L. B. Drobot
N. V. Latyshko
author_sort O. O. Hudkova
collection DOAJ
description 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.
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spelling doaj.art-621ee24ca556462c8eb2757b2cc2b3312023-12-02T14:35:56ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032021-10-01935728110.15407/ubj93.05.072Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in ratsO. O. Hudkova0https://orcid.org/0000-0002-0186-4519I. P. Krysiuk1https://orcid.org/0000-0002-8506-0242T. O. Kishko2N. M. Popova3L. B. Drobot4N. V. Latyshko5Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivThe 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.http://ukrbiochemjournal.org/wp-content/uploads/2021/10/Hudkova_5_21.pdfamine oxidasesantioxidant enzymesbleomycinpulmonary fibrosisredox statesemicarbazide
spellingShingle O. O. Hudkova
I. P. Krysiuk
T. O. Kishko
N. M. Popova
L. B. Drobot
N. V. Latyshko
Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
The Ukrainian Biochemical Journal
amine oxidases
antioxidant enzymes
bleomycin
pulmonary fibrosis
redox state
semicarbazide
title Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
title_full Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
title_fullStr Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
title_full_unstemmed Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
title_short Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
title_sort semicarbazide diminishes the signs of bleomycin induced pulmonary fibrosis in rats
topic amine oxidases
antioxidant enzymes
bleomycin
pulmonary fibrosis
redox state
semicarbazide
url http://ukrbiochemjournal.org/wp-content/uploads/2021/10/Hudkova_5_21.pdf
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AT tokishko semicarbazidediminishesthesignsofbleomycininducedpulmonaryfibrosisinrats
AT nmpopova semicarbazidediminishesthesignsofbleomycininducedpulmonaryfibrosisinrats
AT lbdrobot semicarbazidediminishesthesignsofbleomycininducedpulmonaryfibrosisinrats
AT nvlatyshko semicarbazidediminishesthesignsofbleomycininducedpulmonaryfibrosisinrats