Obiekt
Tytuł: Molecular mechanisms of novel carbon monoxide and hydrogen sulfide donors activity enhancing physiological gastric mucosal integrity against acute drug-induced gastrotoxicity
Abstrakt:
Carbon monoxide (CO) and hydrogen sulfide (H2S) are important gaseous mediators produced endogenously in mammalian tissues. Both molecules exert multidirectional biological activity and participate in many physiological and pathological processes. The aim of this study was to evaluate the molecular mechanism of action of a novel group of CO- or EbS-releasing prodrugs, BW-HS-101 andBW-CO-111 inthe maintenance of the physiological gastric mucosal integrity determining the reduction of gastrotoxicity induced by i.g. administration of acetylsalicylic acid (ASA) as a representative NSAID or comparatively, by ethanol as necrotizing Chemical agent. H2S and CO released from novel prodrugs administered i.g. enhance the physiological protective mucosal barrier within upper GI tract. Thus, these gaseous mediatorsreleasing compounds exert gastroprotective effects against acute gastric mucosal damage induced by direct exposure to ethanol as the Chemical agent and importantly to reduce gastric toxicity induced by the administration of representative drug from the NSAIDs group. Molecular mechanism of the gastroprotective action of BW-HS-101-derived H2S is dependent on endogenous NO biosynthesis and the modulation of the activity of the antiinflammatory SOCS3 signalling, possibly mediated at least in part by the CO/HMOX-1 pathway. The molecular mechanism of BW-CO-lll-mediated gastro ; protection may involve the co-activity of the TGF-β and ANXA1 pathways. The protective effect of BW-CO-lll-derived CO on the gastric mucosa in part due to the maintenance of protective PGE2 level. Both prodrugs, BW-HS-101 and BW-CO-111 showed anti-inflammatory effects at the systemie level and directly within the gastric mucosa.
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Promotor:
Magierowski, Marcin ; Korbut, Edyta
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Data ostatniej modyfikacji:
20 mar 2024
Data dodania obiektu:
3 mar 2023
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http://dl.cm-uj.krakow.pl:8080/publication/4967
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| Nazwa wydania | Data |
|---|---|
| ZB-135928 | 20 mar 2024 |
