title: Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model.
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.
authors.affiliation: a Department of Pathology , Yuzuncu Yil University , Van , Turkey ;
authors.forename: Gulay
authors.initials: G
authors.lastname: Bulut
authors.affiliation: b Faculty of Veterinary Medicine , Yuzuncu Yil University , Van , Turkey ;
authors.forename: Yildiray
authors.initials: Y
authors.lastname: Basbugan
authors.affiliation: c Department of Nephrology , Kartal Training Hospital , Istanbul , Turkey ;
authors.forename: Elif
authors.initials: E
authors.lastname: Ari
authors.affiliation: a Department of Pathology , Yuzuncu Yil University , Van , Turkey ;
authors.forename: Remzi
authors.initials: R
authors.lastname: Erten
authors.affiliation: d Department of Biophysics , Yuzuncu Yil University , Van , Turkey ;
authors.forename: Havva
authors.initials: H
authors.lastname: Bektas
authors.affiliation: e Department of Biochemistry , Yuzuncu Yil University , Van , Turkey.
authors.forename: Hamit Hakan
authors.initials: HH
authors.lastname: Alp
authors.affiliation: a Department of Pathology , Yuzuncu Yil University , Van , Turkey ;
authors.forename: Irfan
authors.initials: I
authors.lastname: Bayram
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000583:Amikacin / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004195:Disease Models, Animal; D004872:Ergocalciferols / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D007677:Kidney Function Tests / Q000379:methods; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D042461:Vascular Endothelial Growth Factor A; D008315:Malondialdehyde; C084656:paricalcitol; D000583:Amikacin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: Amikacin-induced nephrotoxicity; DNA damage; experimental; oxidative stress; paricalcitol