Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy

Nephrology (Carlton). 2012 May;17(4):372-9. doi: 10.1111/j.1440-1797.2012.01565.x.


Aim: Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti-oxidant and anti-apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy.

Methods: Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue.

Results: The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels.

Conclusion: We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers / blood
  • Blood Urea Nitrogen
  • Creatinine / blood
  • Cyclosporine* / blood
  • Cytoprotection
  • Disease Models, Animal
  • Female
  • Grape Seed Extract / pharmacology*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Kidney Diseases / prevention & control*
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Proanthocyanidins / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Antioxidants
  • Biomarkers
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Proanthocyanidins
  • Malondialdehyde
  • Cyclosporine
  • Creatinine