title: Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Nephrology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey. sulusoy2002@yahoo.com
authors.forename: Sukru
authors.initials: S
authors.lastname: Ulusoy
authors.forename: Gulsum
authors.initials: G
authors.lastname: Ozkan
authors.forename: Fulya Balaban
authors.initials: FB
authors.lastname: Yucesan
authors.forename: Şafak
authors.initials: Ş
authors.lastname: Ersöz
authors.forename: Asim
authors.initials: A
authors.lastname: Orem
authors.forename: Mehmet
authors.initials: M
authors.lastname: Alkanat
authors.forename: Esin
authors.initials: E
authors.lastname: Yuluğ
authors.forename: Kubra
authors.initials: K
authors.lastname: Kaynar
authors.forename: Sait
authors.initials: S
authors.lastname: Al
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D008315:Malondialdehyde; D016572:Cyclosporine; D003404:Creatinine