Tag Archives: semicarbazide
Involvement of Cu-containing amine oxidases in the development of lung pathology in ovalbumin-induced bronchial asthma in guinea pigs
O. Hudkova1*, S. Luhovskyi2, L. Drobot1, N. Latyshko1
1Palladin Institute of Biochemistry, National Academy of Sсiences of Ukraine, Kyiv;
2Dmitry F. Chebotarev Institute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv;
*e-mail: ogudkova@biochem.kiev.ua
Received: 03 August 2022; Revised: 15 September 2022;
Accepted: 29 September 2022; Available on-line: 06 October 2022
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 amine oxidases, semicarbazide-sensitive amine oxidase (SSAO), diamine oxidase (DAO), and lysyl oxidase (LOX), in bronchial asthma development we used their irreversible inhibitor, semicarbazide, and ovalbumin-induced pathology in guinea pigs. 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.
Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
O. O. Hudkova*, I. P. Krysiuk, T. O. Kishko,
N. M. Popova, L. B. Drobot, N. V. Latyshko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ogudkova@biochem.kiev.ua
Received: 16 July 2021; Accepted: 22 September 2021
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.
Method for endogenous formaldehyde evaluation in animal organism
S. G. Shandrenko, M. M. Savchyk, M. P. Dmytrenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: shandrenko@biochem.kiev.ua
A method for endogenous formaldehyde (FA) level evaluation has been worked out. The method involves the administration of dimedone, which forms the stable complex with FA, and the determination of formaldimedone concentration in biological samples by the fluorescence approach. The method was tested on rat’s models of FA metabolism modulation. Animals received FA (10 mg/kg); or methylamine – substrate of FA-generating enzyme SSAO, (250 mg/kg); or semicarbazide – SSAO inhibitor, (200mg/kg). Concentration of FA bound with dimedone in the liver tissue were, correspondingly: 7.5 ± 1.5 mkg/kg; 5.4 ± 0.9 mkg/kg; 2.4 ± 0.7 mkg/kg; control – 4.2 ± 1.4 mkg/kg. Obtained data indicate, that the elaborated method gives reliable information about FA level.
Influence of semicarbazide on the peroxidation processes and Lewis carcinoma growth in mice
L. M. Petrun
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: petrun@biochem.kiev.ua
Effects of various doses of semicarbazide on Lewis carcinoma metastasing and peroxidation processes in С57В1 mice have been investigated. In the animals with inoculated Lewis carcinoma, the semicarbazide in the dose of 1/120 LD50 had practical influence on the tumour growth and inhibited the metastasing into mice lungs (P < 0.05). Importantly, this dose significantly inhibited the formation of free radicals and active forms of oxygen against the background of decrease of the aldehydes level that was related to the acceptor properties of the drug.