Lázár, Bernadette and Brenner, Gábor and Makkos, András and Balogh, Mihály and László, Szilvia B and Al-Khrasani, Mahmoud and Hutka, Barbara and Bató, Emese and Ostorházi, Eszter and Juhász, János and Kemény, Ágnes and Horváthné László, Terézia and Tiszlavicz, László and Bihari, Zoltán and Giricz, Zoltán and Szabó, Dóra and Helyes, Zsuzsanna and Ferdinandy, Péter and Gyires, Klára and Zádori, Zoltán Sándor (2019) Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat. CELLS, 8 (3). ISSN 2073-4409
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Abstract
Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFI FK 124878, NVKP-16-1-2016-0017, GINOP-2.3.2.-15-2016-00048, EFOP 3.6.2, EFOP-3.6.3-VEKOP-16-2017-00009]; National Brain Research Program [20017-1.2.1-NKP-2017-00002]; Higher Education Institutional Excellence Programme, within the framework of the Therapeutic Development thematic programme of the Semmelweis University; Ministry of Human Capacities [UNKP-17-4, UNKP-18-3]; Hungarian Academy of Sciences Funding text: The research was supported by the National Research, Development and Innovation Office of Hungary [Grants NKFI FK 124878, NVKP-16-1-2016-0017 National Heart Program, GINOP-2.3.2.-15-2016-00048 "Stay Alive", EFOP 3.6.2. "Live longer", EFOP-3.6.3-VEKOP-16-2017-00009]; the National Brain Research Program [Grant 20017-1.2.1-NKP-2017-00002]; and by the Higher Education Institutional Excellence Programme, within the framework of the Therapeutic Development thematic programme of the Semmelweis University. Zoltan S. Zadori and Mihaly Balogh were supported by the Ministry of Human Capacities [UNKP-17-4 and UNKP-18-3, respectively, New National Excellence Program]. Zoltan Giricz holds a "Janos Bolyai Research Scholarship" from the Hungarian Academy of Sciences. Agnes Kemeny was supported by Janos Bolyai and Bolyai+ Research Scholarships of the Hungarian Academy of Sciences. |
| Uncontrolled Keywords: | CYCLOOXYGENASE-2; Inflammatory Bowel Diseases; ENTEROPATHY; rofecoxib; Microbiota; Intestinal dysbiosis; |
| Subjects: | Q Science / természettudomány > QR Microbiology / mikrobiológia R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 25 Sep 2019 13:13 |
| Last Modified: | 25 Sep 2019 13:13 |
| URI: | http://real.mtak.hu/id/eprint/101198 |
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