Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model. (27th May 2016)

• Record Type: Journal Article
• Authors: Bulut, Gulay; Basbugan, Yildiray; Ari, Elif; Erten, Remzi; Bektas, Havva; Alp, Hamit Hakan; Bayram, Irfan
• Is Part Of: Renal failure. Volume 38:Number 5(2016)
• Page Start: 751
• Page End: 758
• Publication Date: 2016-05-27
• Subjects: Amikacin-induced nephrotoxicity -- DNA damage -- experimental -- oxidative stress -- paricalcitol; Chronic renal failure -- Periodicals; Acute renal failure -- Periodicals; Uremia -- Periodicals; 616.614005
• DOI: 10.3109/0886022X.2016.1158071
• Languages: English
• ISSNs: 0886-022X

Abstract

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 0.4 μg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2 g/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.