N-acetylcysteine attenuates NSAID-induced rat renal failure by restoring intrarenal prostaglandin synthesis

Efrati, Shai; Berman, Sylvia; Siman-Tov, Yariv; Lotan, Raffie; Averbukh, Zhan; Weissgarten, Joshua; Golik, Ahuva

doi:10.1093/ndt/gfm113

Cited by 26 publications

(21 citation statements)

References 35 publications

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“…It seems therefore of great importance that injection of NAC prior to CM administration resulted in an immediate, profound amplification of PGE 2 synthesis that sustained for at least half an hour. Thus far, beneficial effects of NAC treatment have been observed in a number of toxic and ischemic injury models [12,17,18,19,20,21], including CIN [18, 22]. The effects proved to be cell/organ-specific, so it is not surprising that the underlying mechanisms are diverse.…”

Section: Discussionmentioning

confidence: 99%

“…The effects proved to be cell/organ-specific, so it is not surprising that the underlying mechanisms are diverse. With respect to the renoprotective role played by NAC via stimulation of PGE 2 formation, the operative mechanism has been already described in a different renal injury model [18]. In essence, metabolic breakup of arachidonic acid molecule, the endpoint of which is PGE 2 formation, involves oxidation of reduced glutathione, GSH, to the GSSG molecule.…”

Section: Discussionmentioning

confidence: 99%

“…NAC, in turn, is a precursor of the GSH molecule [25]. Surplus of GSH provided by NAC administration would therefore unequivocally result in augmentation of PGE 2 release and consequent vasodilation [18] as, indeed, happened in kidneys of the CM-exposed animals.…”

Section: Discussionmentioning

confidence: 99%

“…Their kidneys were immediately removed, placed on ice, and cortices were separated from medullae. Cytosol extractions were performed from tissue samples of equal weight (1 mg) using the Nuclear Extraction Kit (Chemicon, USA & Canada), as previously described [18]. All the extraction steps were performed on ice, using ice-chilled buffers, according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

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Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction

et al. 2008

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Background: Vasoconstriction and reactive oxygen species (ROS) accumulation following contrast media (CM) injection are the key factors triggering CM-induced nephropathy. We compared the effects of N-acetylcysteine (NAC), theophylline or sodium bicarbonate on intrarenal vasoconstriction and ROS generation in a rat model of CM-induced nephropathy. Methods: Following a 3-day dehydration, Sprague-Dawley rats received CM (Telebrix) or sham ‘CM’ injection of 0.9% saline. Part of them received NAC, theophylline or bicarbonate prior to CM. Medullar renal blood flow was estimated by laser Doppler. The animals were sacrificed 1, 15 or 30 min after the respective treatments, their kidneys allocated and intrarenal STAT-8 isoprostane, PGE₂ and NO assessed. Results: Vasoconstriction was significantly attenuated by NAC. Theophylline only mildly attenuated the perfusion drop at 15 min, and was ineffective following 30 min. Unlike theophylline or bicarbonate, NAC significantly augmented intrarenal PGE₂. NAC, theophylline but not bicarbonate, gradually increased intrarenal NO. In all experimental variables, CM-induced ROS accumulation, represented by STAT-8 isoprostane estimation, progressed undisturbed. Conclusions: (1) CM-induced intrarenal vasoconstriction was efficiently prohibited by NAC but not bicarbonate or theophylline; (2) the vasodilatory effect of NAC was mediated via increased PGE₂ synthesis, and (3) ROS accumulation was a primary renal response to CM-induced injury, not affected by any pharmacologic manipulations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction

et al. 2008

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“…For a given adult of 60–70 kg, this clinical dosage equals 20–35 mg/kg/day, which can be higher than most of the dosages used in experimental rats. For example, NAC concentrations used were 0.5% (∼30.6 m M ) [38] or 40 mg/kg/day [39] in experimental renal diseases. Although most of the studies did not monitor the serum level of NAC, the relatively lower dosage of NAC used in this work to provide some protective effects to HG-induced toxicity implicates that clinical trials to test the effects and safety of NAC in diabetic renal protection may be worthy.…”

Section: Discussionmentioning

confidence: 99%

N-Acetylcysteine-Mediated Antioxidation Prevents Hyperglycemia-Induced Apoptosis and Collagen Synthesis in Rat Mesangial Cells

Hung

Liu

Kao³

et al. 2008

Am J Nephrol

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Background/Aims: High-glucose (HG)-induced mesangial apoptosis and fibrogenesis possibly involves reactive oxygen species (ROS) formation and activated mitochondrial stress. We investigated the therapeutic effect of the antioxidant N-acetylcysteine (NAC) on cellular apoptosis and matrix accumulation in HG-treated rat mesangial cells (RMCs). Methods: RMCs were cultured in media containing 5 (control) or 35 mM (HG) glucose. Cellular apoptosis was assayed by TdT-mediated dUTP nick-end labeling staining. Collagen and transforming growth factor-1 gene expression were measured by reverse transcriptase-polymerase chain reaction or Northern blotting. Mitochondrial capacity and intracellular ROS generation was assayed by fluorescence microscopy and flow cytometry, respectively. Cellular ATP production and malondialdehyde (MDA) formation were determined by a luciferin-luciferase reaction and high-performance liquid chromatography, respectively. Cytochrome c release, caspase activation and poly(ADP)ribose polymerase cleavage were assayed by Western blotting. Results: HG-treated RMCs displayed enhanced cellular apoptosis (65%) and collagen gene expression (1.8-fold increase); these reactions could be significantly suppressed by 1 mM NAC (p < 0.05). Intracellular ROS generation, production of ATP and MDA, and caspase-3, -8 and -9 activities were significantly increased in HG-treated RMCs, and were effectively attenuated by addition of NAC. Conclusion: It is concluded that NAC prevents HG-induced mesangial apoptosis and fibrogenesis pathways by the reduction of oxidative stress.

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Maruf

O’Brien

2015

Oxidative Stress in Applied Basic Research and Clinical Practice

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N-acetylcysteine attenuates NSAID-induced rat renal failure by restoring intrarenal prostaglandin synthesis

Cited by 26 publications

References 35 publications

Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction

Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction

N-Acetylcysteine-Mediated Antioxidation Prevents Hyperglycemia-Induced Apoptosis and Collagen Synthesis in Rat Mesangial Cells

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