5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experimental ischemia/reperfusion

Chatterjee, Prabal K.; Chatterjee, Bristi E.; Pedersen, Helene Pape; Sivarajah, Ahila; McDonald, Michelle C.; Mota-Filipe, Hélder; Brown, Paul A.J.; Stewart, Keith Nicol; Cuzzocrea, Salvatore; Threadgill, Michael D.; Thiemermann, Christoph

doi:10.1111/j.1523-1755.2004.00415.x

Cited by 52 publications

(38 citation statements)

References 43 publications

(40 reference statements)

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“…Paradoxically, excessive activation of PARP from cellular injury leads to intracellular NAD ϩ and to ATP depletion, ultimately resulting in cell death. PARP overactivation has been known to play a role in the pathogenesis of IRI to kidney, heart, and brain (53)(54)(55). Inhibition of PARP immediately at reperfusion reduced injury.…”

Section: Antiapoptosis/necrosis Agentsmentioning

confidence: 99%

Pharmacologic Treatment of Acute Kidney Injury

Rosner

Okusa

2007

Clinical Journal of the American Society of Nephrology

243

178

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Current strategies to limit the extent of injury in acute renal failure are based on extensive studies that identified cellular and molecular mechanisms of acute kidney injury. Despite successes in various animal models, translation to human studies has failed or studies are inconclusive. This review describes past failures and barriers to successful clinical trials. It also focuses on promising preclinical studies using novel compounds that currently are in or close to human investigation. Implementation of previous or novel compounds in well-designed clinical trials provides hope for the successful treatment of this devastating disorder.

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Section: Antiapoptosis/necrosis Agentsmentioning

confidence: 99%

Pharmacologic Treatment of Acute Kidney Injury

Rosner

Okusa

2007

Clinical Journal of the American Society of Nephrology

243

178

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“…[4,5] Importantly, sepsis is a leading cause of acute renal failure (ARF), which is an important factor leading to an increase in mortality. [6][7][8][9] Currently, there are no pharmaceutical agents available to improve the clinical outcome of ARF, as treatment is directed toward nutritional and supportive care. [10,11] However, precise mechanisms that lead to ARF during endotoxemia remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Poly (ADP-Ribose) Polymerase as a Potential Target for the Treatment of Acute Renal Injury Caused by Lipopolysaccharide

Taşatargil¹,

Aksoy²,

Dalaklıoğlu³

et al. 2008

Renal Failure

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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-β-dglucosaminidase (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 LPSinduced renal impairment. Hence, pharmacological inhibition of this pathway might be an effective intervention to prevent endotoxin-induced acute renal injury.

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“…Two isoforms of PARG are ubiquitously expressed, a 110-kD isoform (PARG 110 ), localized mainly in the nucleus, and a 60-kD isoform (PARG 60 ), localized in the cytoplasm (5). Although both isoforms exhibit exo-and endoglycosidase activity, PARG 110 is the major form of PARG in the nucleus (6,7) Inhibitors of PARP activity reduce the tissue injury caused by I/R of the heart (8,9), brain (10), gut (11), liver (12), and kidney (13). Most notable, the degree of tissue injury caused by I/R in the heart (14), brain (15), gut (16), and most recently kidney (17) is reduced in mice in which the gene encoding for PARP-1 has been disrupted (PARP-1 Ϫ/Ϫ mice).…”

mentioning

confidence: 99%