<i>N</i>-acetyl-<scp>l</scp>-cysteine improves renal medullary hypoperfusion in acute renal failure

Conesa, Erica López; Valero, Fernando; Nadal, José Carlos; Fenoy, Francisco J.; López, Bernardo; Arregui, Begoña; Salom, Miguel G.

doi:10.1152/ajpregu.2001.281.3.r730

Cited by 119 publications

(102 citation statements)

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“…In our work,NAC preincubation reduces ONOO À anion release without affecting O À 2 anion production after an in vitro overnight treatment of SSc macrophages. These data are in agreement with early reports showing similar NAC effects on different cell types [23][24][25] and in vivo [26].…”

Section: Discussionsupporting

confidence: 94%

“…The formation of these nitrothiol compounds can preserve and accumulate NO in a biologically active form. A similar mechanism could explain the NAC protective effect described by Conesa and coauthors in their acute renal failure in vivo model [26] in which the presence of NO is essential for attempting NAC beneficial effect. On the other hand, NAC is unable to modify the O À 2 production, ruling out a scavenging effect on this ROS.…”

Section: Discussionsupporting

confidence: 60%

“…According to recent data, NAC can prevent peroxynitrite-mediated oxidation in a model of ischemia-reperfusion in the rat [24] and directly reduces ONOO À formation in rat macrophages obtained from the pleural cavity in a model of carrageenan-induced pleurisy [25]. Moreover, in an acute model of renal failure produced by inferior vena cava occlusion the protective effect of NAC is dependent on the scavenging of ONOO À and is observed only when NO is physiologically produced, since the N G -nitro-L L -arginine methyl ester NOS inhibitor abolishes it [26]. Therefore, the aim of our study was to determine the iNOS expression and the effectiveness of NAC treatment in the reduction of the ONOO À and O À 2 anion production in lung alveolar macrophages obtained from BAL of SSc patients.…”

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confidence: 99%

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Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

et al. 2002

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Lung macrophages may play a relevant role in oxidative processes producing both superoxide anion ðO À 2 Þ and NO. In this view, an antioxidant therapy can be useful in the treatment of systemic sclerosis (SSc) patients. N-Acetylcysteine (NAC) is able to expand natural antioxidant defenses by increasing intracellular gluthatione concentration and it has been proposed as an antioxidant therapy in respiratory distress syndromes. The aim of our study was to determine whether lung macrophages obtained from SSc patient bronchoalveolar lavage (BAL) express the inducible form of nitric oxide synthase (iNOS) and whether NAC can reduce the peroxynitrite ðONOO À Þ and O À 2 production of these cells. Alveolar macrophages were isolated from BAL of 32 patients and used for the immunocytochemical determination of iNOS, and the production of ONOO À and O À 2 was measured by fluorimetric or spectrophotometric methods, respectively. Lung macrophages obtained from SSc patients expressed a higher level of iNOS compared to healthy subject cells. NAC preincubation (5 Â 10 À5 M, 24 h) significantly reduced ()21%) the ONOO À production in formyl Met-Leu-Phe (fMLP)-activated cells and slightly reduced it under resting conditions, whereas NAC preincubation was unable to modify the release of O À 2 both in basal condition and in fMLP-stimulated cells. We conclude that since SSc lung macrophages express high levels of iNOS and produce a significant quantity of ONOO À , NAC administration reduces ONOO À production and can be an useful treatment to alleviate SSc symptoms. Ó 2002 Elsevier Science (USA). All rights reserved.Keywords: Systemic sclerosis; Inducible nitric oxide synthase; N-acetylcysteine; Peroxynitrite; Superoxide anion; Alveolar macrophages Nitric oxide (NO) 1 is physiologically produced by constitutive nitric oxide synthase isoforms (cNOS) and in several pathophysiological conditions by an inducible nitric oxide synthase isoform (iNOS). In systemic sclerosis (SSc) patients, NO is increased in exhaled air [1,2] while it is decreased in those patients with pulmonary hypertension [2,3]. Moreover, serum NO levels are enhanced [4], iNOS is highly expressed in mononuclear cells infiltrating the skin [4] and peripheral blood mononuclear cells produce increased NO levels when stimulated with IL-1 [5]. NO can be synthesized by different kinds of cells. Among these cells, macrophages play a pivotal role in the inflammatory infiltrate and, in patients with tubercolosis, iNOS is expressed in alveolar macrophages [6]. Inflammatory cells produce reactive oxygen species (ROS) that, reacting with NO, form tissue-damaging NO-derived inflammatory oxidants. ROS

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 60%

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confidence: 99%

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Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

et al. 2002

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“…61 Also, Conesaet al found that NAC reduced renal vasoconstriction and improved renal blood flow. 62 The observed increases in SOD, CAT and GSH levels in NAC and MT pretreated rats could be attributed to the stimulatory synthesis and regeneration of these endogenous antioxidants by NAC and MT. MT has been reported to stimulate the activities of endogenous antioxidants and increase gene expression that improves the total antioxidant defense capacity of organisms.…”

Section: Discussionmentioning

confidence: 94%

Prospects of N-Acetylcysteine and Melatonin as Treatments for Tramadol-Induced Renal Toxicity in Albino Rats

Adikwu¹,

Bokolo²

2017

Pharm Sci

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“…15,16 It also preserved renal function in animal models of ischemic kidney-injury. 17,18 N-acetylcysteine has already been studied extensively for preventing contrast-induced nephropathy. Despite initial promise, its efficacy in this setting has not been proven definitively.…”

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confidence: 99%

N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency

Wijeysundera

Beattie

Rao

et al. 2007

Can J Anesth/J Can Anesth

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Purpose: N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial. Methods:One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR ≤ 60 mL·min -1 ) were recruited in a blinded (patients, clinicians, datacollectors) placebo-controlled randomized trial. Eighty-nine were randomized to N-acetylcysteine (100 mg·kg -1 iv bolus, 20 mg·kg -1 ·hr -1 infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was the percent change in eGFR during the first 72 postoperative hours. Secondary outcomes included renal replacement therapy, mortality, atrial fibrillation, vasoactive medications, and adverse effects. A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better (small benefit), and with an upper 95% confidence interval including 9.5 (moderate benefit). Results: The median percent change in eGFR was 5.2% better (absolute difference) in the N-acetylcysteine arm (95% confidence interval 2.4% worse to 12.1% better; P = 0.22). With regard to secondary outcomes, all-cause mortality was lower in the N-acetylcysteine arm (0% vs 8%; P = 0.007). Conclusion:N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this singlecentre study. Nonetheless, its treatment effect was consistent with a plausible small-to-moderate benefit. Given this finding, N-acetylcysteine should be definitively evaluated in a large randomized trial.

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N-acetyl-l-cysteine improves renal medullary hypoperfusion in acute renal failure

Cited by 119 publications

References 27 publications

Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

Prospects of N-Acetylcysteine and Melatonin as Treatments for Tramadol-Induced Renal Toxicity in Albino Rats

N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency

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