Your browser doesn't support javascript.
loading
Modulation of Prostanoids Profile and Counter-Regulation of SDF-1α/CXCR4 and VIP/VPAC2 Expression by Sitagliptin in Non-Diabetic Rat Model of Hepatic Ischemia-Reperfusion Injury.
Krzystek-Korpacka, Malgorzata; Fleszar, Mariusz G; Fortuna, Paulina; Gostomska-Pampuch, Kinga; Lewandowski, Lukasz; Piasecki, Tomasz; Kosyk, Bogna; Szelag, Adam; Trocha, Malgorzata.
Afiliación
  • Krzystek-Korpacka M; Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
  • Fleszar MG; Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
  • Fortuna P; Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
  • Gostomska-Pampuch K; Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
  • Lewandowski L; Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
  • Piasecki T; Department of Epizootiology and Clinic of Bird and Exotic Animals, Wroclaw University of Environmental and Life Sciences, 50-366 Wroclaw, Poland.
  • Kosyk B; Institute of Soil Science and Environmental Protection, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
  • Szelag A; Department of Pharmacology, Wroclaw Medical University, 50-345 Wroclaw, Poland.
  • Trocha M; Department of Pharmacology, Wroclaw Medical University, 50-345 Wroclaw, Poland.
Int J Mol Sci ; 22(23)2021 Dec 05.
Article en En | MEDLINE | ID: mdl-34884960
Molecular mechanisms underlying the beneficial effect of sitagliptin repurposed for hepatic ischemia-reperfusion injury (IRI) are poorly understood. We aimed to evaluate the impact of IRI and sitagliptin on the hepatic profile of eicosanoids (LC-MS/MS) and expression/concentration (RTqPCR/ELISA) of GLP-1/GLP-1R, SDF-1α/CXCR4 and VIP/VPAC1, VPAC2, and PAC1 in 36 rats. Animals were divided into four groups and subjected to ischemia (60 min) and reperfusion (24 h) with or without pretreatment with sitagliptin (5 mg/kg) (IR and SIR) or sham-operated with or without sitagliptin pretreatment (controls and sitagliptin). PGI2, PGE2, and 13,14-dihydro-PGE1 were significantly upregulated in IR but not SIR, while sitagliptin upregulated PGD2 and 15-deoxy-12,14-PGJ2. IR and sitagliptin non-significantly upregulated GLP-1 while Glp1r expression was borderline detectable. VIP concentration and Vpac2 expression were downregulated in IR but not SIR, while Vpac1 was significantly downregulated solely in SIR. IRI upregulated both CXCR4 expression and concentration, and sitagliptin pretreatment abrogated receptor overexpression and downregulated Sdf1. In conclusion, hepatic IRI is accompanied by an elevation in proinflammatory prostanoids and overexpression of CXCR4, combined with downregulation of VIP/VPAC2. Beneficial effects of sitagliptin during hepatic IRI might be mediated by drug-induced normalization of proinflammatory prostanoids and upregulation of PGD2 and by concomitant downregulation of SDF-1α/CXCR4 and reinstating VIP/VCAP2 signaling.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Prostaglandinas / Fosfato de Sitagliptina / Hepatopatías Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Prostaglandinas / Fosfato de Sitagliptina / Hepatopatías Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Suiza