Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110
The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic proper...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1500 |
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| author | Anna A. Brezgunova Nadezda V. Andrianova Aleena A. Saidova Daria M. Potashnikova Polina A. Abramicheva Vasily N. Manskikh Sofia S. Mariasina Irina B. Pevzner Ljubava D. Zorova Igor V. Manzhulo Dmitry B. Zorov Egor Y. Plotnikov |
| author_facet | Anna A. Brezgunova Nadezda V. Andrianova Aleena A. Saidova Daria M. Potashnikova Polina A. Abramicheva Vasily N. Manskikh Sofia S. Mariasina Irina B. Pevzner Ljubava D. Zorova Igor V. Manzhulo Dmitry B. Zorov Egor Y. Plotnikov |
| author_sort | Anna A. Brezgunova |
| collection | DOAJ |
| description | The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic properties. The aim of this study was to investigate the anti-inflammatory effect of synaptamide in ischemic AKI. For this purpose, we analyzed the expression of inflammatory mediators and the infiltration of different leukocyte populations into the kidney after injury, evaluated the expression of the putative synaptamide receptor G-protein-coupled receptor 110 (GPR110), and isolated a population of CD11b/c<sup>+</sup> cells mainly representing neutrophils and macrophages using cell sorting. We also evaluated the severity of AKI during synaptamide therapy and the serum metabolic profile. We demonstrated that synaptamide reduced the level of pro-inflammatory interleukins and the expression of integrin CD11a in kidney tissue after injury. We found that the administration of synaptamide increased the expression of its receptor GPR110 in both total kidney tissue and renal CD11b/c<sup>+</sup> cells that was associated with the reduced production of pro-inflammatory interleukins in these cells. Thus, we demonstrated that synaptamide therapy mitigates the inflammatory response in kidney tissue during ischemic AKI, which can be achieved through GPR110 signaling in neutrophils and a reduction in these cells’ pro-inflammatory interleukin production. |
| first_indexed | 2024-03-08T03:55:46Z |
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| id | doaj.art-918e4ef1f0f7442d90ba07ebf5fa0151 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:46Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-918e4ef1f0f7442d90ba07ebf5fa01512024-02-09T15:13:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253150010.3390/ijms25031500Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110Anna A. Brezgunova0Nadezda V. Andrianova1Aleena A. Saidova2Daria M. Potashnikova3Polina A. Abramicheva4Vasily N. Manskikh5Sofia S. Mariasina6Irina B. Pevzner7Ljubava D. Zorova8Igor V. Manzhulo9Dmitry B. Zorov10Egor Y. Plotnikov11A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaFaculty of Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaFaculty of Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaThe development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic properties. The aim of this study was to investigate the anti-inflammatory effect of synaptamide in ischemic AKI. For this purpose, we analyzed the expression of inflammatory mediators and the infiltration of different leukocyte populations into the kidney after injury, evaluated the expression of the putative synaptamide receptor G-protein-coupled receptor 110 (GPR110), and isolated a population of CD11b/c<sup>+</sup> cells mainly representing neutrophils and macrophages using cell sorting. We also evaluated the severity of AKI during synaptamide therapy and the serum metabolic profile. We demonstrated that synaptamide reduced the level of pro-inflammatory interleukins and the expression of integrin CD11a in kidney tissue after injury. We found that the administration of synaptamide increased the expression of its receptor GPR110 in both total kidney tissue and renal CD11b/c<sup>+</sup> cells that was associated with the reduced production of pro-inflammatory interleukins in these cells. Thus, we demonstrated that synaptamide therapy mitigates the inflammatory response in kidney tissue during ischemic AKI, which can be achieved through GPR110 signaling in neutrophils and a reduction in these cells’ pro-inflammatory interleukin production.https://www.mdpi.com/1422-0067/25/3/1500kidneyischemia/reperfusionacute kidney injuryinflammationsynaptamidetherapy |
| spellingShingle | Anna A. Brezgunova Nadezda V. Andrianova Aleena A. Saidova Daria M. Potashnikova Polina A. Abramicheva Vasily N. Manskikh Sofia S. Mariasina Irina B. Pevzner Ljubava D. Zorova Igor V. Manzhulo Dmitry B. Zorov Egor Y. Plotnikov Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110 International Journal of Molecular Sciences kidney ischemia/reperfusion acute kidney injury inflammation synaptamide therapy |
| title | Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110 |
| title_full | Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110 |
| title_fullStr | Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110 |
| title_full_unstemmed | Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110 |
| title_short | Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110 |
| title_sort | anti inflammatory effect of synaptamide in ischemic acute kidney injury and the role of g protein coupled receptor 110 |
| topic | kidney ischemia/reperfusion acute kidney injury inflammation synaptamide therapy |
| url | https://www.mdpi.com/1422-0067/25/3/1500 |
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