Effect of cell permeable peptide of c-Jun NH2-terminal kinase inhibitor on the attenuation of renal ischemia-reperfusion injury in pigs

Transplant Proc. 2013 Jul-Aug;45(6):2469-75. doi: 10.1016/j.transproceed.2013.02.134.

Abstract

The outcomes of organ transplantation have improved due to better immunosuppressive drugs, surgical techniques, and management of complications. However, ischemia-reperfusion injury remains a challenge affecting graft survival. In this study, we employed injection of a protein transduction domain (PTD) to inhibit the c-Jun NH2-terminal kinase (JNK) pathway thereby attenuating ischemia-reperfusion injury in a porcine model. The PTD-JNK inhibitor (JNKI) was administered into the renal artery, allowing it to be taken into various elements including vascular endothelial cells by endocytosis via the PTD. Serum creatinine and blood urea nitrogen concentrations were lower among PTD-JNKI than controls. In addition, renal tissue blood flow was maintained in the PTD-JNKI group, resulting in less tissue injury and fewer apoptotic cells. These results suggested that the PTD technique improved renal transplantation outcomes.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Blood Urea Nitrogen
  • Cell Membrane Permeability
  • Cell-Penetrating Peptides / administration & dosage
  • Cell-Penetrating Peptides / metabolism
  • Cell-Penetrating Peptides / pharmacology*
  • Cold Ischemia / adverse effects
  • Creatinine / blood
  • Cytoprotection
  • Disease Models, Animal
  • Endocytosis
  • Female
  • Injections, Intra-Arterial
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / enzymology
  • Kidney / pathology
  • Kidney Diseases / enzymology
  • Kidney Diseases / etiology
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Renal Artery
  • Renal Circulation / drug effects
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Swine
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Resistance / drug effects

Substances

  • Biomarkers
  • Cell-Penetrating Peptides
  • Protein Kinase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Creatinine
  • JNK Mitogen-Activated Protein Kinases