Lathyrus sativus diamine oxidase reduces Clostridium difficile toxin A-induced toxicity in Caco-2 cells by rescuing RhoA-GTPase and inhibiting pp38-MAPK/NF-κB/HIF-1α activation.

Autor: Pietrangeli P; Department of Biochemical Sciences 'A. Rossi Fanelli', Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy., Corpetti C; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University of Rome, Rome, Italy., Seguella L; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University of Rome, Rome, Italy., Del Re A; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University of Rome, Rome, Italy., Pesce M; Department of Clinical Medicine and Surgery, section of Gastroenterology, University Federico II, Naples, Italy., Vincenzi M; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University of Rome, Rome, Italy., Lori C; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University of Rome, Rome, Italy., Annunziata G; Department of Pharmacy, University Federico II, Naples, Italy., Mateescu MA; Department of Chemistry and Centre CERMO-FC, Université du Québec à Montreal, CP8888 Branch A, Montreal (Québec), Montreal, Québec, Canada., Sarnelli G; Department of Clinical Medicine and Surgery, section of Gastroenterology, University Federico II, Naples, Italy., Esposito G; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University of Rome, Rome, Italy., Marcocci L; Department of Biochemical Sciences 'A. Rossi Fanelli', Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2021 Jan; Vol. 35 (1), pp. 415-423. Date of Electronic Publication: 2020 Sep 10.
DOI: 10.1002/ptr.6814
Abstrakt: Clostridium difficile toxin A (TcdA) impairs the intestinal epithelial barrier, increasing the mucosa permeability and triggering a robust inflammatory response. Lathyrus sativus diamino oxidase (LSAO) is a nutraceutical compound successfully used in various gastrointestinal dysfunctions. Here, we evaluated the LSAO (0.004-0.4 μM) ability to counter TcdA-induced (30 ng/mL) toxicity and damage in Caco-2 cells, investigating its possible mechanism of action. LSAO has improved the transepithelial electrical resistance (TEER) score and increased cell viability in TcdA-treated cells, significantly rescuing the protein expression of Ras homolog family members, A-GTPase (RhoA-GTPase), occludin, and zonula occludens-1 (ZO-1). LSAO has also exhibited an anti-apoptotic effect by inhibiting the TcdA-induced expression of Bcl-2-associated X protein (Bax), p50 nuclear factor-kappa-B (p50), p65nuclear factor-kappa-B (p65), and hypoxia-inducible transcription factor-1 alpha (HIF-1α), and the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) in the cell milieu. Our data showed that LSAO exerts a protective effect on TcdA-induced toxicity in Caco-2 cells, placing itself as an interesting nutraceutical to supplement the current treatment of the Clostridium difficile infections.
(© 2020 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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