Empagliflozin attenuates intestinal inflammation through suppression of nitric oxide synthesis and myeloperoxidase activity in in vitro and in vivo models of colitis
© 2023. The Author(s)..
Inflammatory bowel diseases (IBD) are characterized by chronic and relapsing inflammation affecting the gastrointestinal (GI) tract. The incidence and prevalence of IBD are relatively high and still increasing. Additionally, current therapeutic strategies for IBD are not optimal. These facts urge todays' medicine to find a novel way to treat IBD. Here, we focused on the group of anti-diabetic drugs called gliflozins, which inhibit sodium glucose co-transporter type 2 (SGLT-2). Numerous studies demonstrated that gliflozins exhibit pleiotropic effect, including anti-inflammatory properties. In this study, we tested the effect of three gliflozins; empagliflozin (EMPA), dapagliflozin (DAPA), and canagliflozin (CANA) in in vitro and in vivo models of intestinal inflammation. Our in vitro experiments revealed that EMPA and DAPA suppress the production of nitric oxide in LPS-treated murine RAW264.7 macrophages. In in vivo part of our study, we showed that EMPA alleviates acute DSS-induced colitis in mice. Treatment with EMPA reduced macro- and microscopic colonic damage, as well as partially prevented from decrease in tight junction gene expression. Moreover, EMPA attenuated biochemical inflammatory parameters including reduced activity of myeloperoxidase. We showed that SGLT-2 inhibitors act as anti-inflammatory agents independently from their hypoglycemic effects. Our observations suggest that gliflozins alleviate inflammation through their potent effects on innate immune cells.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
|---|---|
| Enthalten in: |
Inflammopharmacology - 32(2024), 1 vom: 21. Feb., Seite 377-392 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Makaro, Adam [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s10787-023-01227-8 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM355900319 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM355900319 | ||
| 003 | DE-627 | ||
| 005 | 20240306232251.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10787-023-01227-8 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1318.xml |
| 035 | |a (DE-627)NLM355900319 | ||
| 035 | |a (NLM)37086302 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Makaro, Adam |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Empagliflozin attenuates intestinal inflammation through suppression of nitric oxide synthesis and myeloperoxidase activity in in vitro and in vivo models of colitis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.03.2024 | ||
| 500 | |a Date Revised 05.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Inflammatory bowel diseases (IBD) are characterized by chronic and relapsing inflammation affecting the gastrointestinal (GI) tract. The incidence and prevalence of IBD are relatively high and still increasing. Additionally, current therapeutic strategies for IBD are not optimal. These facts urge todays' medicine to find a novel way to treat IBD. Here, we focused on the group of anti-diabetic drugs called gliflozins, which inhibit sodium glucose co-transporter type 2 (SGLT-2). Numerous studies demonstrated that gliflozins exhibit pleiotropic effect, including anti-inflammatory properties. In this study, we tested the effect of three gliflozins; empagliflozin (EMPA), dapagliflozin (DAPA), and canagliflozin (CANA) in in vitro and in vivo models of intestinal inflammation. Our in vitro experiments revealed that EMPA and DAPA suppress the production of nitric oxide in LPS-treated murine RAW264.7 macrophages. In in vivo part of our study, we showed that EMPA alleviates acute DSS-induced colitis in mice. Treatment with EMPA reduced macro- and microscopic colonic damage, as well as partially prevented from decrease in tight junction gene expression. Moreover, EMPA attenuated biochemical inflammatory parameters including reduced activity of myeloperoxidase. We showed that SGLT-2 inhibitors act as anti-inflammatory agents independently from their hypoglycemic effects. Our observations suggest that gliflozins alleviate inflammation through their potent effects on innate immune cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DSS-induced colitis | |
| 650 | 4 | |a Empagliflozin | |
| 650 | 4 | |a Inflammatory bowel diseases | |
| 650 | 4 | |a SGLT-2 | |
| 650 | 7 | |a empagliflozin |2 NLM | |
| 650 | 7 | |a HDC1R2M35U |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 650 | 7 | |a Sodium-Glucose Transporter 2 Inhibitors |2 NLM | |
| 650 | 7 | |a dapagliflozin |2 NLM | |
| 650 | 7 | |a 1ULL0QJ8UC |2 NLM | |
| 650 | 7 | |a Benzhydryl Compounds |2 NLM | |
| 650 | 7 | |a Glucosides |2 NLM | |
| 700 | 1 | |a Świerczyński, Mikołaj |e verfasserin |4 aut | |
| 700 | 1 | |a Pokora, Kacper |e verfasserin |4 aut | |
| 700 | 1 | |a Sarniak, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Kordek, Radzisław |e verfasserin |4 aut | |
| 700 | 1 | |a Fichna, Jakub |e verfasserin |4 aut | |
| 700 | 1 | |a Salaga, Maciej |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Inflammopharmacology |d 1996 |g 32(2024), 1 vom: 21. Feb., Seite 377-392 |w (DE-627)NLM090686616 |x 1568-5608 |7 nnns |
| 773 | 1 | 8 | |g volume:32 |g year:2024 |g number:1 |g day:21 |g month:02 |g pages:377-392 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s10787-023-01227-8 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 32 |j 2024 |e 1 |b 21 |c 02 |h 377-392 | ||