Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats
Background The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment. Methods Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats. Results Canagliflozin increased the colonic glucose concentration and restored the number of Lactobacillus bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin. Conclusions The increases in colonic glucose concentration, Lactobacillus numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Clinical and experimental nephrology - 27(2023), 4 vom: 07. Jan., Seite 295-308 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Matsui, Ayumi [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
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| Anmerkungen: |
© The Author(s), under exclusive licence to The Japanese Society of Nephrology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s10157-022-02312-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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SPR049720686 |
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| 520 | |a Background The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment. Methods Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats. Results Canagliflozin increased the colonic glucose concentration and restored the number of Lactobacillus bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin. Conclusions The increases in colonic glucose concentration, Lactobacillus numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats. | ||
| 650 | 4 | |a Canagliflozin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chronic kidney disease |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Gut microbiota |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Yoshifuji, Ayumi |4 aut | |
| 700 | 1 | |a Irie, Junichiro |4 aut | |
| 700 | 1 | |a Tajima, Takaya |4 aut | |
| 700 | 1 | |a Uchiyama, Kiyotaka |4 aut | |
| 700 | 1 | |a Itoh, Tomoaki |4 aut | |
| 700 | 1 | |a Wakino, Shu |4 aut | |
| 700 | 1 | |a Itoh, Hiroshi |4 aut | |
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