Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat
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 we...
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MDPI AG
2019-03-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/8/3/251 |
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| author | Bernadette Lázár Gábor B. Brenner András Makkos Mihály Balogh Szilvia B. László Mahmoud Al-Khrasani Barbara Hutka Emese Bató Eszter Ostorházi János Juhász Ágnes Kemény Terézia László László Tiszlavicz Zoltán Bihari Zoltán Giricz Dóra Szabó Zsuzsanna Helyes Péter Ferdinandy Klára Gyires Zoltán S. Zádori |
| author_facet | Bernadette Lázár Gábor B. Brenner András Makkos Mihály Balogh Szilvia B. László Mahmoud Al-Khrasani Barbara Hutka Emese Bató Eszter Ostorházi János Juhász Ágnes Kemény Terézia László László Tiszlavicz Zoltán Bihari Zoltán Giricz Dóra Szabó Zsuzsanna Helyes Péter Ferdinandy Klára Gyires Zoltán S. Zádori |
| author_sort | Bernadette Lázár |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:12:59Z |
| format | Article |
| id | doaj.art-447f416e8ec148d5adc5ca8abc2b227f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:12:59Z |
| publishDate | 2019-03-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-447f416e8ec148d5adc5ca8abc2b227f2023-08-02T05:44:17ZengMDPI AGCells2073-44092019-03-018325110.3390/cells8030251cells8030251Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the RatBernadette Lázár0Gábor B. Brenner1András Makkos2Mihály Balogh3Szilvia B. László4Mahmoud Al-Khrasani5Barbara Hutka6Emese Bató7Eszter Ostorházi8János Juhász9Ágnes Kemény10Terézia László11László Tiszlavicz12Zoltán Bihari13Zoltán Giricz14Dóra Szabó15Zsuzsanna Helyes16Péter Ferdinandy17Klára Gyires18Zoltán S. Zádori19Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungarySecond Department of Internal Medicine and Cardiology Center, University of Szeged, 6725 Szeged, HungaryInstitute of Medical Microbiology, Semmelweis University, 1089 Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, 1083 Budapest, HungaryDepartment of Medical Biology, University of Pécs, 7624 Pécs, HungaryDepartment of Pathology, University of Pécs, 7624 Pécs, HungaryDepartment of Pathology, University of Szeged, 6725 Szeged, HungaryXenovea Ltd., 6726 Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryInstitute of Medical Microbiology, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, 7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryIntestinal 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.http://www.mdpi.com/2073-4409/8/3/251microbiotaintestinal dysbiosisinflammatory bowel diseasescyclooxygenase-2rofecoxibenteropathy |
| spellingShingle | Bernadette Lázár Gábor B. Brenner András Makkos Mihály Balogh Szilvia B. László Mahmoud Al-Khrasani Barbara Hutka Emese Bató Eszter Ostorházi János Juhász Ágnes Kemény Terézia László László Tiszlavicz Zoltán Bihari Zoltán Giricz Dóra Szabó Zsuzsanna Helyes Péter Ferdinandy Klára Gyires Zoltán S. Zádori Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat Cells microbiota intestinal dysbiosis inflammatory bowel diseases cyclooxygenase-2 rofecoxib enteropathy |
| title | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
| title_full | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
| title_fullStr | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
| title_full_unstemmed | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
| title_short | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
| title_sort | lack of small intestinal dysbiosis following long term selective inhibition of cyclooxygenase 2 by rofecoxib in the rat |
| topic | microbiota intestinal dysbiosis inflammatory bowel diseases cyclooxygenase-2 rofecoxib enteropathy |
| url | http://www.mdpi.com/2073-4409/8/3/251 |
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