Everolimus Pretreatment Protects the Lung From Ischemia-Reperfusion Injury

Authors

  • Şevki Mustafa Demiröz Gazi University Medical School, Department of Thoracic Surgery, Ankara, Türkiye
  • Ali Celik Gazi University Medical School, Department of Thoracic Surgery, Ankara, Türkiye
  • Ilke Hacer Onen Gazi University Medical School, Department of Medical Biology, Ankara, Türkiye
  • Ece Konac Gazi University Medical School, Department of Medical Biology, Ankara, Türkiye
  • Erdem Vargol Sakarya University Training and Research Hospital, Department of Pathology, Sakarya, Türkiye
  • Nalan Akyurek Gazi University Medical School, Department of Pathology, Ankara, Türkiye
  • Ozge Tugce Pasaoglu Gazi University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Ankara, Türkiye
  • Hatice Pasaoglu Gazi University Medical School, Department of Medical Biochemistry, Ankara, Türkiye
  • ISmail Cuneyt Kurul

Keywords:

lung ischemi-reperfusion, everolimus, inflammation, experimental model, qPCR

Abstract

Purposes: A preventive strategy against lung ischemia reperfusion injury (LIRI) is pretreatment with certain drugs to make them more resistant to LIRI. The aim of this study was to investigate the preventive effects of everolimus (RAD001) on LIRI in a rat-ventilated ischemia-reperfusion model.

Methods:Rats were divided into 8 groups;1 control(I), 6 LIRI (IIa,b,c;IIIa,b,c) and  1 everolimus (IV). LIRI groups underwent 90 min of ischemia and 30 min (IIa-IIIa), 120 min (IIb-IIIb)  and 240min (IIc-IIIc) of reperfusion, respectively, and were randomized into two, one without (II) and one with everolimus (III)  pretreatment. Groups III received 1mg/kg/day everolimus via oral gavage for 1 week before IR. After reperfusion, bronchoalveolar lavage and lung tissue samples were collected. The mRNA expressions of the samples’ pro-inflammatory genes were determined via qPCR. TNF-α and macrophage inflammatory protein 2 (MIP2) concentrations and caspase-3 activity were measured using ELISA kits. Also, myeloperoxidase (MPO) activity was measured spectrophotometrically.

Results:Everolimus significantly decreased the expression of all study mRNA pro-inflammatory genes for groups IIIb and IIIc(p<0.05). It also decreased MIP2 protein levels in groups IIIb and IIIc, whereas TNF-α protein levels decreased only in group IIIc’s lung tissue samples(p<0.05). A significant downregulation of caspase-3 enzyme activity was detected only in group IIIa(p<0.05).

Conclusion:This study shows that everolimus pretreatment, effectively prevents LIRI by decreasing pro-inflammatory genes’ mRNA expressions, the protein expressions of TNF-α and MIP2, and the activity of caspase 3 and myeloperoxidase.

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Published

10.03.2023

Issue

Vol. 34 No. 2 (2023): Gazi Medical Journal

Section

Original Research

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