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ORIGINAL ARTICLE  BIOTECHNOLOGICAL AND PHARMACOLOGICAL DEVELOPMENTS IN THE MODIFICATION OF CHRONIC INFLAMMATION-INDUCED DISEASES 

Minerva Biotechnology and Biomolecular Research 2021 June;33(2):117-24

DOI: 10.23736/S2724-542X.21.02758-9

Copyright © 2021 EDIZIONI MINERVA MEDICA

language: English

Anti-inflammatory hydrogen sulfide-releasing agents with reduced gastro- and enterotoxicity on the stress model in rats

Iryna FOMENKO 1 , Iryna LOZYNSKA 1, Tetyana BONDARCHUK 1, Natalia DENYSENKO 1, Roman LESYK 2, Alexander SKLYAROV 1

1 Department of Biochemistry, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine; 2 Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine



BACKGROUND: The new approaches of modern anti-inflammatory therapy are based on the synthesis of hydrogen sulfide-releasing hybrids of anti-inflammatory drugs or on the inhibition of the main pro-inflammatory enzymes. The aim of this study was to explore effects of novel thiazolidinone-based derivatives that possess dual cyclooxygenase and lipoxygenase inhibitory activity as a novel donors of hydrogen sulfide in promoting the resolution of inflammation in gastro-intestinal tract of rats under condition of stress.
METHODS: Water restraint stress was used to induce lesions in gastrointestinal tract of rats, three types of novel thiazolidine-based derivatives which inhibit cyclooxygenase and lipoxygenase were administered 30 minutes prior to stress. In the gastric, small and large intestinal mucosa were determined: alterations in hydrogen sulfide and nitric oxide concentrations, changes in activity of myeloperoxidase, nitric oxide synthases, arginase, catalase and superoxide dismutase.
RESULTS: Increased activity of myeloperoxidase, inducible nitric oxide synthase, intensification of lipid peroxidation and drop in hydrogen sulfide production in gastrointestinal mucosa of rats subjected to water restraint stress were observed. Compound 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxothiazolidin-4-one demonstrated significant beneficial effects, manifested by normalization of parameters of nitric oxide system and oxidative stress.
CONCLUSIONS: 5-(3,5-di-tert-butyl-4- hydroxybenzylidene)-2-thioxothiazolidin-4-one possess reduced gastro- and enterotoxicity in gastrointestinal tract of rats under condition of stress what can explained by the release of hydrogen sulfide in gastrointestinal tract and dual inhibition of cyclooxygenase and lipoxygenase.


KEY WORDS: Inflammation; Stress disorders, traumatic, acute; Hydrogen sulfide; Gastrointestinal tract

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