Renal injury induced in alloxan diabetic rats. Role of Mycophenolate Mofetil as therapeutic agent

Pathol Res Pract. 2014 Dec;210(12):979-84. doi: 10.1016/j.prp.2014.05.014. Epub 2014 May 23.

Abstract

Background: Renal injury may develop in uncontrolled chronic hyperglycemia due to increased oxidative stress and release of pro-inflammatory mediators, leading to diabetic complications.

Methods: Mycophenolate Mofetil (MMF) is an immunosuppressant drug, an inhibitor of inosine monophosphate dehydrogenase (IMPDH), relevant to inflammation processes. MMF effect was tested in alloxan-diabetic rats on selected parameters like oxidative stress, gene expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1), in relation to microalbuminuria and renal function.

Results: We found that the onset of microalbuminuria preceded the increase in serum glucose after alloxan treatment. Gene expression of TNF-α and TGF-β1 showed gradual increase after one and two weeks of alloxan administration as compared to the normal group. MMF administration decreased the gene expression of TNF-α and TGF-β1 in kidney tissues, serum glucose, fructosamine, urea, creatinine, C-reactive protein, malondialdehyde, urinary microalbumin and total protein. Histological examination of kidney tissues showed significant improvement in MMF treated rats as compared to diabetic control.

Conclusions: MMF modulated renal injury of alloxan diabetic rats. Collective data may support its therapeutic effect but further clinical trials may be requested.

Keywords: Malondialdehyde; Mycophenolate Mofetil; Nephropathy; Transforming growth factor-beta1; Tumor necrosis factor-alpha.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / pathology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Mycophenolic Acid / therapeutic use
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Immunosuppressive Agents
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Mycophenolic Acid