Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion
A possibility of repurposing sitagliptin, a well-established antidiabetic drug, for alleviating injury caused by ischemia-reperfusion (IR) is being researched. The aim of this study was to shed some light on the molecular background of the protective activity of sitagliptin during hepatic IR. The ex...
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MDPI AG
2021-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/8/1168 |
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| author | Małgorzata Trocha Mariusz G. Fleszar Paulina Fortuna Łukasz Lewandowski Kinga Gostomska-Pampuch Tomasz Sozański Anna Merwid-Ląd Małgorzata Krzystek-Korpacka |
| author_facet | Małgorzata Trocha Mariusz G. Fleszar Paulina Fortuna Łukasz Lewandowski Kinga Gostomska-Pampuch Tomasz Sozański Anna Merwid-Ląd Małgorzata Krzystek-Korpacka |
| author_sort | Małgorzata Trocha |
| collection | DOAJ |
| description | A possibility of repurposing sitagliptin, a well-established antidiabetic drug, for alleviating injury caused by ischemia-reperfusion (IR) is being researched. The aim of this study was to shed some light on the molecular background of the protective activity of sitagliptin during hepatic IR. The expression and/or concentration of inflammation and oxidative stress-involved factors have been determined in rat liver homogenates using quantitative RT-PCR and Luminex<sup>®</sup> xMAP<sup>®</sup> technology and markers of nitrative and halogenative stress were quantified using targeted metabolomics (LC-MS/MS). Animals (n = 36) divided into four groups were treated with sitagliptin (5 mg/kg) (S and SIR) or saline solution (C and IR), and the livers from IR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). The midkine expression (by 2.2-fold) and the free 3-nitrotyrosine (by 2.5-fold) and IL-10 (by 2-fold) concentration were significantly higher and the <i>Nox4</i> expression was lower (by 9.4-fold) in the IR than the C animals. As compared to IR, the SIR animals had a lower expression of interleukin-6 (by 4.2-fold) and midkine (by 2-fold), a lower concentration of 3-nitrotyrosine (by 2.5-fold) and a higher <i>Nox4</i> (by 2.9-fold) and 3-bromotyrosine (by 1.4-fold). In conclusion, IR disturbs the oxidative, nitrative and halogenative balance and aggravates the inflammatory response in the liver, which can be attenuated by low doses of sitagliptin. |
| first_indexed | 2024-03-10T09:03:40Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:40Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-c0ff3ac3f08c428da84768a8f4f0f2c32023-11-22T06:35:05ZengMDPI AGAntioxidants2076-39212021-07-01108116810.3390/antiox10081168Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-ReperfusionMałgorzata Trocha0Mariusz G. Fleszar1Paulina Fortuna2Łukasz Lewandowski3Kinga Gostomska-Pampuch4Tomasz Sozański5Anna Merwid-Ląd6Małgorzata Krzystek-Korpacka7Department of Pharmacology, Wroclaw Medical University, 50-345 Wroclaw, PolandDepartment of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Pharmacology, Wroclaw Medical University, 50-345 Wroclaw, PolandDepartment of Pharmacology, Wroclaw Medical University, 50-345 Wroclaw, PolandDepartment of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandA possibility of repurposing sitagliptin, a well-established antidiabetic drug, for alleviating injury caused by ischemia-reperfusion (IR) is being researched. The aim of this study was to shed some light on the molecular background of the protective activity of sitagliptin during hepatic IR. The expression and/or concentration of inflammation and oxidative stress-involved factors have been determined in rat liver homogenates using quantitative RT-PCR and Luminex<sup>®</sup> xMAP<sup>®</sup> technology and markers of nitrative and halogenative stress were quantified using targeted metabolomics (LC-MS/MS). Animals (n = 36) divided into four groups were treated with sitagliptin (5 mg/kg) (S and SIR) or saline solution (C and IR), and the livers from IR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). The midkine expression (by 2.2-fold) and the free 3-nitrotyrosine (by 2.5-fold) and IL-10 (by 2-fold) concentration were significantly higher and the <i>Nox4</i> expression was lower (by 9.4-fold) in the IR than the C animals. As compared to IR, the SIR animals had a lower expression of interleukin-6 (by 4.2-fold) and midkine (by 2-fold), a lower concentration of 3-nitrotyrosine (by 2.5-fold) and a higher <i>Nox4</i> (by 2.9-fold) and 3-bromotyrosine (by 1.4-fold). In conclusion, IR disturbs the oxidative, nitrative and halogenative balance and aggravates the inflammatory response in the liver, which can be attenuated by low doses of sitagliptin.https://www.mdpi.com/2076-3921/10/8/1168drug repurposingdipeptidylpeptidase-4 antagonistsmidkinebromotyrosinenitrotyrosineliver transplantation |
| spellingShingle | Małgorzata Trocha Mariusz G. Fleszar Paulina Fortuna Łukasz Lewandowski Kinga Gostomska-Pampuch Tomasz Sozański Anna Merwid-Ląd Małgorzata Krzystek-Korpacka Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion Antioxidants drug repurposing dipeptidylpeptidase-4 antagonists midkine bromotyrosine nitrotyrosine liver transplantation |
| title | Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion |
| title_full | Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion |
| title_fullStr | Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion |
| title_full_unstemmed | Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion |
| title_short | Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion |
| title_sort | sitagliptin modulates oxidative nitrative and halogenative stress and inflammatory response in rat model of hepatic ischemia reperfusion |
| topic | drug repurposing dipeptidylpeptidase-4 antagonists midkine bromotyrosine nitrotyrosine liver transplantation |
| url | https://www.mdpi.com/2076-3921/10/8/1168 |
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