Experimental Lung Transplantation Related With HIF-1, VEGF, ROS. Assessment of HIF-1alpha, VEGF, and Reactive Oxygen Species After Competitive Blockade of Chetomin for Lung Transplantation in Rats

Physiol Res. 2024 Nov 19;73(5):809-817. doi: 10.33549/physiolres.935385.

Abstract

Primary graft failure occurs 15 to 30 % of the time after transplantation. Although there have been improvements in preserving the lungs in good condition, there have not been studies on the regulation of transcription factors.

Methods: We carried out an experimental study involving lung transplantation to indirectly evaluate reactive oxygen species (ROS) production and VEGF expression by competitive blockade of HIF-1alpha with chetomin. There were 5 groups: Group-1: Lung blocks were perfused with 0.9 % SSF, immediately harvested, and preserved. Group-2 (I-T): Immediate transplantation and then reperfusion for 1 h. Group-3 (I-R): Lung blocks were harvested and preserved in LPD solution for 6 h and reperfused for 1 h. Group-4 (DMSO): Lung blocks were treated for 4 h with DMSO, preserved for 6 h and transplanted to a receptor treated with DMSO. Group-5 (chetomin): Lung blocks were treated for 4 h with chetomin, preserved for 6 h and transplanted to a receptor treated with chetomin. ROS, mRNA, and protein levels of HIF-1alpha and EG-VEGF were determined.

Results: The DMSO and chetomin groups had significantly lower ROS levels. Compared with those in the I-R group, the chetomin group exhibited the lowest level of HIF-1alpha.

Conclusions: Addition of chetomin to the donor and the receptor results in a significant reduction in HIF-1A, VEGF and ROS.

MeSH terms

  • Animals
  • Disulfides
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Indole Alkaloids
  • Lung / drug effects
  • Lung / metabolism
  • Lung Transplantation*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species* / metabolism
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A
  • Hif1a protein, rat
  • chetomin
  • vascular endothelial growth factor A, rat
  • Disulfides
  • Indole Alkaloids