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Updated: Aug 29, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experimental ischemia/reperfusion
Prabal K Chatterjee1, Bristi E Chatterjee, Helene Pedersen
1Department of Experimental Medicine, Nephrology & Critical Care, The William Harvey Research Institute, Queen Mary-University of London, United Kingdom.
Background:
Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5-AIQ), on the renal injury and dysfunction caused by oxidative stress of the rat kidney in vitro and in vivo.
Methods:
Primary cultures of rat renal proximal tubular cells, subjected to oxidative stress caused by hydrogen peroxide (H2O2), were incubated with increasing concentrations of 5-AIQ (0.01 to 1 mmol/L) after which PARP activation, cellular injury, and cell death were measured. In in vivo experiments, anesthetized male Wistar rats were subjected to renal bilateral ischemia (45 minutes) followed by reperfusion (6 hours) in the absence or presence of 5-AIQ (0.3 mg/kg) after which renal dysfunction, injury and PARP activation were assessed.
Results:
Incubation of proximal tubular cells with H2O2 caused a substantial increase in PARP activity, cellular injury, and cell death, which were all significantly reduced in a concentration-dependent by 5-AIQ [inhibitory concentration 50 (IC50) approximately 0.03 mmol/L]. In vivo, renal I/R resulted in renal dysfunction, injury, and PARP activation, primarily in the proximal tubules of the kidney. Administration of 5-AIQ significantly reduced the biochemical and histologic signs of renal dysfunction and injury and markedly reduced PARP activation caused by I/R.
Conclusion:
This study demonstrates that 5-AIQ is a potent, water soluble inhibitor of PARP activity, which can significantly reduce (1) cellular injury and death caused to primary cultures of rat proximal tubular cells by oxidative stress in vitro, and (2) renal injury and dysfunction caused by I/R of the kidney of the rat in vivo.
Insights
The potent PARP inhibitor 5-aminoisoquinolinone (5-AIQ) significantly reduces oxidative stress-induced cell damage in rat kidney cells. In vivo, 5-AIQ also protects against ischemia/reperfusion injury, demonstrating its therapeutic potential.
Area of Science:
- Biochemistry
- Nephrology
- Pharmacology
Background:
- Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme implicated in DNA repair and cellular stress responses.
- PARP activation is a key factor in the pathogenesis of ischemia/reperfusion (I/R) injury, particularly in the kidney.
- Oxidative stress contributes significantly to renal damage during I/R events.
Purpose of the Study:
- To investigate the efficacy of 5-aminoisoquinolinone (5-AIQ), a water-soluble PARP inhibitor, in mitigating renal injury.
- To evaluate the protective effects of 5-AIQ against oxidative stress-induced damage in rat kidney cells in vitro.
- To assess the impact of 5-AIQ on renal dysfunction and injury caused by I/R in vivo.
Main Methods:
- Primary rat renal proximal tubular cells were exposed to hydrogen peroxide (H2O2) to induce oxidative stress and treated with varying concentrations of 5-AIQ.
- PARP activation, cellular injury, and cell death were quantified in vitro.
- Male Wistar rats underwent bilateral renal ischemia followed by reperfusion, with or without 5-AIQ administration.
- Renal function, histological injury, and PARP activation were assessed in vivo.
Main Results:
- 5-AIQ demonstrated a concentration-dependent reduction in PARP activation, cellular injury, and cell death in H2O2-treated proximal tubular cells (IC50 ≈ 0.03 mmol/L).
- Renal I/R in rats led to significant dysfunction, injury, and PARP activation, primarily in proximal tubules.
- Administration of 5-AIQ markedly attenuated the biochemical and histological markers of renal dysfunction and injury, and suppressed I/R-induced PARP activation.
Conclusions:
- 5-AIQ is confirmed as a potent and water-soluble inhibitor of PARP activity.
- 5-AIQ effectively reduces oxidative stress-induced cellular damage in vitro.
- 5-AIQ significantly mitigates renal injury and dysfunction associated with I/R in vivo, highlighting its therapeutic potential.
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