Organic carbon monoxide prodrug, BW-CO-111, in protection against chemically-induced gastric mucosal damage
| Autor: | Binghe Wang, Jakub Cieszkowski, Urszula Głowacka, Grzegorz Ginter, Zbigniew Śliwowski, Zhixiang Pan, Tomasz Brzozowski, Grzegorz Buszewicz, Dominik Bakalarz, Marcin Surmiak, Edyta Korbut, Dagmara Wojcik, Marcin Magierowski, Katarzyna Magierowska, Xiaoxiao Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
HMOX1
Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Oral administration Anti-inflammation medicine Gastric mucosa General Pharmacology Toxicology and Pharmaceutics Carbon monoxide Prodrug 030304 developmental biology 0303 health sciences Aspirin Ethanol Chemistry lcsh:RM1-950 Gastric mucosal damage NSAID Interleukin 10 medicine.anatomical_structure lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis Interleukin 12 Original Article Gastroprotection medicine.drug |
| Zdroj: | Acta Pharmaceutica Sinica B, Vol 11, Iss 2, Pp 456-475 (2021) Acta Pharmaceutica Sinica. B |
| ISSN: | 2211-3835 |
| Popis: | Metal-based carbon monoxide (CO)-releasing molecules have been shown to exert anti-inflammatory and anti-oxidative properties maintaining gastric mucosal integrity. We are interested in further development of metal-free CO-based therapeutics for oral administration. Thus, we examine the protective effect of representative CO prodrug, BW-CO-111, in rat models of gastric damage induced by necrotic ethanol or aspirin, a representative non-steroidal anti-inflammatory drug. Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry. Gastric mucosal mRNA and/or protein expressions of HMOX1, HMOX2, nuclear factor erythroid 2-related factor 2, COX1, COX2, iNos, Anxa1 and serum contents of TGFB1, TGFB2, IL1B, IL2, IL4, IL5, IL6, IL10, IL12, tumor necrosis factor α, interferon γ, and GM-CSF were determined. CO content in gastric mucosa was assessed by gas chromatography. Pretreatment with BW-CO-111 (0.1 mg/kg, i.g.) increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF. These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers. However, because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin, the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models. Graphical abstract Carbon monoxide (CO) is an endogenous molecule exerting anti-inflammatory activity. BW-CO-111 is an organic CO prodrug. BW-CO-111 exerts gastroprotective effect against ethanol- and aspirin-induced damage. The specific mechanism of the beneficial activity of CO released from BW-CO-111 depends on the type of gastric tissue injury.Image 1 |
| Databáze: | OpenAIRE |
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