Role of the poly(ADP-ribose)polymerase activity in vancomycin-induced renal injury

Dalaklioglu S., Tekcan M., Gungor N. E., Celik-Ozenci C., Aksoy N. H., Baykal A., ...Daha Fazla

TOXICOLOGY LETTERS, cilt.192, sa.2, ss.91-96, 2010 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 192 Sayı: 2
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1016/j.toxlet.2009.10.002
  • Dergi Adı: TOXICOLOGY LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.91-96
  • Anahtar Kelimeler: PARP, Renal injury, Rat, Vancomycin, TARGETING SUPEROXIDE-DISMUTASE, OXIDE SYNTHASE INHIBITION, PROXIMAL TUBULE CELLS, ADP-RIBOSE POLYMERASE, BRUSH-BORDER MEMBRANE, NF-KAPPA-B, INDUCED NEPHROTOXICITY, LIPOPOLYSACCHARIDE, RAT, DYSFUNCTION
  • Akdeniz Üniversitesi Adresli: Evet

Özet

The aim of the present study was to investigate the role of poly(ADP-ribose)polymerase (PARP) activity in vancomycin (VCM)-induced renal injury and to determine whether 1,5-isoquinelinediol (ISO). a PARP inhibitor agent, could be offered as an alternative therapy in VCM-induced renal impairment. Rats were divided into four groups as follows: (i) control (Group 1); (ii) VCM-treated (Group 2): (iii) VCM plus ISO-treated (Group 3); and (iv) ISO-treated (Group 4). VCM (200 mg/kg, i.p., twice daily) was administered to Groups 2 and 3 for 7 days. ISO (3 mg/kg/day, i.p.) treatment was started 24 h before the first administration of VCM and continued for 8 days. After the 14th VCM injection, the animals were placed in metabolic cages to collect urine samples. All the rats were sacrificed by decapitation, blood samples were taken in tubes and kidneys were excised immediately. Blood urea nitrogen (BUN) and plasma creatinine, and urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) were used as markers of VCM-induced renal injury in rats. Light microscopy was used to evaluate semi-quantitative analysis of the kidney sections. Poly(ADP-ribose) (PAR, the product of activated PARP) and PARP-1 expressions in renal tissues were demonstrated by immunohistochemistry and Western blot. VCM administration increased BUN levels from 8.07 +/- 0.75 mg/dL to 53.87 +/- 10.11 mg/dL The plasma creatinine levels were 0.8 +/- 0.04 mg/dL and 3.38 +/- 0.51 mg/dL for the control and VCM-treated groups, respectively. Also, urinary excretion of NAG was increased after VCM injection. Besides, there was a significant dilatation of the renal tubules, eosinophilic casts within some tubules, desquamation and vacuolization of renal tubule epithelium, and interstitial tissue inflammation in VCM-treated rats. In VCM-treated rats, both PAR and PARP-1 expressions were increased in renal tubular cells. ISO treatment attenuated VCM-induced renal injury, as indicated by BUN and plasma creatinine levels, urinary NAG excretion, and renal histology. PARP inhibitor treatment also decreased PAR and PARP-1 protein expressions similar to that of controls. Herewith, the overactivation of the PARP pathway may have a role in VCM-induced renal impairment and pharmacological inhibition of this pathway might be an effective intervention to prevent VCM-induced acute renal injury. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Role of the poly(ADP-ribose)polymerase activity in vancomycin-induced renal injury

By:Dalaklioglu, S (Dalaklioglu, Selvinaz)[ 1 ] ; Tekcan, M (Tekcan, Merih)[ 2 ] ; Gungor, NE (Gungor, Nazli Ece)[ 2 ] ; Celik-Ozenci, C (Celik-Ozenci, Ciler)[ 2 ] ; Aksoy, NH (Aksoy, Nazif Hikmet)[ 3 ] ; Baykal, A (Baykal, Asli)[ 4 ] ; Tasatargil, A (Tasatargil, Arda)[ 5 ]

 

TOXICOLOGY LETTERS

 

Volume: 192

Issue: 2

Pages: 91-96

DOI: 10.1016/j.toxlet.2009.10.002

Published: FEB 1 2010

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TOXICOLOGY LETTERS

JCR® Category Quartile in Category
TOXICOLOGY Q2

Data from the 2012 edition of Journal Citation Reports®

Publisher ELSEVIER IRELAND LTD, ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND

ISSN: 0378-4274

Research Domain Toxicology

Abstract

The aim of the present study was to investigate the role of poly(ADP-ribose)polymerase (PARP) activity in vancomycin (VCM)-induced renal injury and to determine whether 1,5-isoquinelinediol (ISO). a PARP inhibitor agent, could be offered as an alternative therapy in VCM-induced renal impairment. Rats were divided into four groups as follows: (i) control (Group 1); (ii) VCM-treated (Group 2): (iii) VCM plus ISO-treated (Group 3); and (iv) ISO-treated (Group 4). VCM (200 mg/kg, i.p., twice daily) was administered to Groups 2 and 3 for 7 days. ISO (3 mg/kg/day, i.p.) treatment was started 24 h before the first administration of VCM and continued for 8 days. After the 14th VCM injection, the animals were placed in metabolic cages to collect urine samples. All the rats were sacrificed by decapitation, blood samples were taken in tubes and kidneys were excised immediately. Blood urea nitrogen (BUN) and plasma creatinine, and urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) were used as markers of VCM-induced renal injury in rats. Light microscopy was used to evaluate semi-quantitative analysis of the kidney sections. Poly(ADP-ribose) (PAR, the product of activated PARP) and PARP-1 expressions in renal tissues were demonstrated by immunohistochemistry and Western blot. VCM administration increased BUN levels from 8.07 +/- 0.75 mg/dL to 53.87 +/- 10.11 mg/dL The plasma creatinine levels were 0.8 +/- 0.04 mg/dL and 3.38 +/- 0.51 mg/dL for the control and VCM-treated groups, respectively. Also, urinary excretion of NAG was increased after VCM injection. Besides, there was a significant dilatation of the renal tubules, eosinophilic casts within some tubules, desquamation and vacuolization of renal tubule epithelium, and interstitial tissue inflammation in VCM-treated rats. In VCM-treated rats, both PAR and PARP-1 expressions were increased in renal tubular cells. ISO treatment attenuated VCM-induced renal injury, as indicated by BUN and plasma creatinine levels, urinary NAG excretion, and renal histology. PARP inhibitor treatment also decreased PAR and PARP-1 protein expressions similar to that of controls. Herewith, the overactivation of the PARP pathway may have a role in VCM-induced renal impairment and pharmacological inhibition of this pathway might be an effective intervention to prevent VCM-induced acute renal injury. (C) 2009 Elsevier Ireland Ltd. All rights reserved.