Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model


Bulut G., Başbuğan Y., Ari E., Erten R., Bektas H., Alp H. H., ...More

RENAL FAILURE, vol.38, no.5, pp.751-758, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 5
  • Publication Date: 2016
  • Doi Number: 10.3109/0886022x.2016.1158071
  • Journal Name: RENAL FAILURE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.751-758
  • Keywords: Amikacin-induced nephrotoxicity, DNA damage, experimental, oxidative stress, paricalcitol, COMBINATION THERAPY, KIDNEY, EXPRESSION, INJURY, ACID
  • Van Yüzüncü Yıl University Affiliated: Yes

Abstract

This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n=32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A+P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4g/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A+P had lower mean fractional sodium excretion (p<0.001) as well as higher creatinine clearance (p=0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p=0.035) and serum 8-hydroxy-2-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p<0.001) were significantly lower; superoxide dismutase (p=0.024) and glutathione peroxidase (p=0.007) activities of renal tissue were significantly higher in group A+P than in group A. The mean scores of tubular necrosis (p=0.024), proteinaceous casts (p=0.038), medullary congestion (p=0.035), and VEGF immunoexpression (p=0.018) were also lower in group A+P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model.