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H2S confers colonoprotection against TNBS-induced colitis by HO-1 upregulation in rats

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Abstract

Hydrogen sulfide (H2S) is an endogenous mediator that contributes to many important physiological processes including vasodilation and vascular smooth muscle relaxation; in turn, preventing tissue damage and reducing inflammation. Heme oxygenase (HO) enzymes, of which HO-1 is inducible by harmful stimuli, were found to regulate intestinal inflammation in experimental animal models of colitis. We aimed to investigate the protective effects of H2S against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, and whether HO enzyme system is involved in the H2S-induced colonic cytoprotection. Male Wistar rats were treated with TNBS to induce colitis, and H2S donor (Lawesson’s reagent) was prepared two times/day at different concentrations, and delivered per os (from day 1 to day 3). Our results suggest that daily treatment (2 times/day) with H2S donor, could significantly decrease the extent of colonic inflammation compared to vehicle treatment, and the most effective daily dose of H2S donor against inflammation was 18.75 µM/kg/day. Per os administration of H2S donor increased the colonic HO enzyme activity; on the contrary, the protective effect of H2S was abolished by the co-treatment with HO inhibitor. Our findings suggest that H2S confers colonoprotection, probably by modulation of anti-inflammatory parameters and HO enzyme activity.

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Acknowledgements

This research was realized in the frames of TÁMOP 4.2.4. A/2-11-1-2012-0001 National Excellence Program—Elaborating and operating an inland student and researcher personal support system. The project was subsidized by the European Union and co-financed by the European Social Fund (Krisztina Kupai). It was supported also by the ÚNKP-ÚNKP-16-4 New National Excellence Program of the Ministry of Human Capacities (Anikó Pósa) and GINOP-2.3.2-15-2016-00030.

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Authors and Affiliations

  1. Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, 6726, Szeged, Hungary

    Krisztina Kupai, Nikoletta Almási, Szilvia Török, Amin Al-awar, Anikó Pósa & Csaba Varga

  2. Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, University of Szeged, 6720, Szeged, Hungary

    Zoltán Baráth

  3. College of Arts and Sciences, Sport Science Program, Qatar University, Doha, Qatar

    Zsolt Murlasits

  4. Department of Pediatrics, Faculty of Medicine, University of Szeged, 6720, Szeged, Hungary

    Magdolna Kósa

  5. Department of Biology, J. Selye University, Komárno, Slovakia

    János Nemcsók

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  1. Krisztina Kupai
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  2. Nikoletta Almási
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Correspondence to Krisztina Kupai.

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Kupai, K., Almási, N., Kósa, M. et al. H2S confers colonoprotection against TNBS-induced colitis by HO-1 upregulation in rats. Inflammopharmacol 26, 479–489 (2018). https://doi.org/10.1007/s10787-017-0382-8

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