Poly (ADP-ribose) polymerase as a potential target for the treatment of acute renal injury caused by lipopolysaccharide

Renal Failure
Arda TasatargilGulay Sadan

Abstract

Recent studies have clearly reported that there is a relationship between endotoxemia and acute renal injury. The aim of this study was to investigate whether treatment with the new potent PARP inhibitor PJ34 could prevent the acute renal injury induced by lipopolysaccharide (LPS). Endotoxemia was induced by LPS injection (10 mg/kg, i.v.). LPS increased blood urea nitrogen (BUN) levels from 22 +/- 0.54 mg/dL to 45.7 +/- 5.79 mg/dL (p < 0.05). The plasma creatinine levels were 0.38 +/- 0.02 mg/dL and 0.47 +/- 0.03 mg/dL for the control and LPS groups, respectively. In addition, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular damage) was increased after LPS injection. By light microscopy, structural renal damage was observed in the LPS-treated group. However, PJ34 treatment (10 mg/kg, i.p.) attenuated LPS-induced renal injury, as indicated by plasma BUN and creatinine levels, urinary NAG excretion, and renal histology. These results indicated that the overactivation of the PARP pathway may have a role in LPS-induced renal impairment. Hence, pharmacological inhibition of this pathway might be an effective intervention to prevent endotoxin-induced acute renal injury.

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Citations

May 2, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Samuel N HeymanChristian Rosenberger
Oct 17, 2009·Toxicology Letters·Selvinaz DalakliogluArda Tasatargil
Dec 7, 2013·Journal of Receptor and Signal Transduction Research·Tian-Biao Zhou, Zong-Pei Jiang
Feb 2, 2013·Molecular Aspects of Medicine·Nicola J Curtin, Csaba Szabo
Aug 24, 2012·International Journal of Toxicology·Selvinaz DalakliogluArda Tasatargil
Aug 29, 2009·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Arda TasatargilBedriniam Dalkiran
Jun 8, 2019·Pharmacological Reports : PR·Nazli Ece Gungor-OrdueriCiler Celik-Ozenci
Nov 19, 2014·Molecular and Cellular Biochemistry·Kunal KapoorAmarjit S Naura

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