Mycophenolate mofetil inhibits macrophage infiltration and kidney fibrosis in long-term ischemia-reperfusion injury

Eur J Pharmacol. 2012 Aug 5;688(1-3):56-61. doi: 10.1016/j.ejphar.2012.05.001. Epub 2012 May 16.

Abstract

Immunosuppressants have been widely used in renal transplantation, in which ischemia-reperfusion injury is inevitable. Mycophenolate mofetil (MMF) is a relative novel immunosuppressant and also attenuates ischemia-reperfusion injury in the acute phase, but its long-term effects are still obscure. Unilateral renal ischemia-reperfusion injury model was established in Sprague-Dawley rats and 30 mg/kg/day MMF or natural saline was administered a day before the surgery. Renal function was monitored, and histological changes and fibrosis in the kidney were evaluated in both short and long terms. TGF-β1 secretion and MCP-1 expression were determined by immunohistochemistry and real-time PCR respectively. The infiltration of macrophages in renal tissues was also assessed by fluorescence activated cell sorting (FACS). MMF treatment significantly improved renal function in ischemia-reperfusion injury rats in the short and long-term and also effectively prevented interstitial fibrosis. TGF-β1 secretion and MCP-1 expression in the renal tissue of MMF-treated rats were much lower than those in natural saline-treated rats, with much less macrophage infiltration as well. MMF treatment effectively prevented the deterioration of renal function and interstitial fibrosis in ischemia-reperfusion injury rats, which may be associated with decreased TGF-β1, MCP-1 and macrophages. These results provide evidence for the choice of MMF in the renal transplant patients not only for acute renal injury but also for long-term survival of renal allograft.

MeSH terms

  • Animals
  • Chemokine CCL2 / metabolism
  • Dose-Response Relationship, Drug
  • Fibrosis
  • Gene Expression Regulation / drug effects
  • Immunosuppressive Agents / pharmacology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney / physiopathology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • Reperfusion Injury / physiopathology
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Ccl2 protein, rat
  • Chemokine CCL2
  • Immunosuppressive Agents
  • Transforming Growth Factor beta1
  • Mycophenolic Acid