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Article

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

1
Department of Pharmacology, Wroclaw Medical University, 50-345 Wroclaw, Poland
2
Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Eszter Mária Horváth
Antioxidants 2021, 10(8), 1168; https://doi.org/10.3390/antiox10081168
Received: 13 June 2021 / Revised: 19 July 2021 / Accepted: 20 July 2021 / Published: 22 July 2021
(This article belongs to the Special Issue Oxidative-Nitrative Stress in Human Health and Disease)
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® xMAP® 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 Nox4 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 Nox4 (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. View Full-Text
Keywords: drug repurposing; dipeptidylpeptidase-4 antagonists; midkine; bromotyrosine; nitrotyrosine; liver transplantation; NADPH oxidase (NOX); hepatoprotection drug repurposing; dipeptidylpeptidase-4 antagonists; midkine; bromotyrosine; nitrotyrosine; liver transplantation; NADPH oxidase (NOX); hepatoprotection
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MDPI and ACS Style

Trocha, M.; Fleszar, M.G.; Fortuna, P.; Lewandowski, Ł.; Gostomska-Pampuch, K.; Sozański, T.; Merwid-Ląd, A.; Krzystek-Korpacka, M. Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion. Antioxidants 2021, 10, 1168. https://doi.org/10.3390/antiox10081168

AMA Style

Trocha M, Fleszar MG, Fortuna P, Lewandowski Ł, Gostomska-Pampuch K, Sozański T, Merwid-Ląd A, Krzystek-Korpacka M. Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion. Antioxidants. 2021; 10(8):1168. https://doi.org/10.3390/antiox10081168

Chicago/Turabian Style

Trocha, Małgorzata, Mariusz G. Fleszar, Paulina Fortuna, Łukasz Lewandowski, Kinga Gostomska-Pampuch, Tomasz Sozański, Anna Merwid-Ląd, and Małgorzata Krzystek-Korpacka. 2021. "Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion" Antioxidants 10, no. 8: 1168. https://doi.org/10.3390/antiox10081168

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