Pretreatment of cisplatin in recipients attenuates post-transplantation pancreatitis in murine model

Int J Biol Sci. 2012;8(3):298-309. doi: 10.7150/ijbs.3656. Epub 2012 Feb 1.

Abstract

Pancreas transplantation is the definite treatment for type 1 diabetes that enables the achievement of long-term normoglycemia and insulin independence. However Post-Transplantation Pancreatitis (PTP) due to ischemia reperfusion (IR) injury and preservation is a major complication in pancreas transplantation. Owning the potential anti-inflammatory effect of Cisplatin (Cis) in liver IR injury, we have examined if Cis could attenuate PTP using a murine model. We found that Cis is able to prevent inflammatory response in PTP. Pretreatment of Cis in recipient mice reduce the impairments of the grafts and hyperamylasimea in the recipients. We documented that the protective mechanism of Cis in PTP involves improvement of microcirculation, reduction of the mononuclear cellular infiltration and apoptosis, suppression of inflammatory cytokine-cascade and inhibition of translocation of high-motility group box protein-1 (HMGB-1) from nucleus to cytoplasm. In short, our study demonstrated that pretreatment of Cis in recipients may reduce the onset of PTP in pancreas transplantation.

Keywords: Cisplatin; High-motility group box protein-1; Intravital fluorescence microscopy.; Ischemia reperfusion injury; Pancreatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cisplatin / administration & dosage
  • Cisplatin / therapeutic use*
  • Drug Evaluation, Preclinical
  • Graft Rejection / prevention & control*
  • HMGB1 Protein / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microcirculation
  • Microscopy, Fluorescence
  • Pancreas / blood supply
  • Pancreas / drug effects
  • Pancreas / ultrastructure
  • Pancreas Transplantation*
  • Pancreatitis / etiology
  • Pancreatitis / prevention & control*
  • Postoperative Complications / etiology
  • Postoperative Complications / prevention & control*
  • Premedication*
  • Protein Transport / drug effects
  • Specific Pathogen-Free Organisms

Substances

  • Anti-Inflammatory Agents
  • HMGB1 Protein
  • Cisplatin