Alteration in plasma levels of nonprotein sulfhydryl compounds and S-nitrosothiols in chronic renal failure patients

Włodek, Przemysław J; Kucharczyk, Justyna; Sokołowska, Maria; Miłkowski, A; Markiewicz, Adam; Smoleński, O; Włodek, Lidia

doi:10.1016/s0009-8981(02)00339-x

Cited by 18 publications

(11 citation statements)

References 21 publications

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“…Furthermore, Wlodek et al (22) observed plasma S-nitrosothiol concentrations different from those observed in our study, but they used L-cysteine to obtain a standard calibration curve, whereas we used reduced glutathione to obtain the calibration curve. A direct comparison of the results obtained with the two methods is therefore difficult.…”

Section: Discussioncontrasting

confidence: 87%

Increased Plasma S-Nitrosothiol Concentrations Predict Cardiovascular Outcomes among Patients with End-Stage Renal Disease

Massy¹,

Fumeron²,

Borderie³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. The plasma concentrations of S-nitrosothiols, which are circulating nitric oxide metabolites with potential biologic activity, are increased among patients undergoing chronic hemodialysis (HD). However, the ability of S-nitrosothiols to release nitric oxide at physiologically relevant sites may be reduced among HD patients, because of impaired availability and/or activity of factors involved in S-nitrosothiol breakdown. The resultant lack of S-nitrosothiol bioavailability could contribute to the high cardiovascular risk for such patients. A possible relationship between plasma S-nitrosothiol levels and cardiac outcomes, as well as all-cause mortality rates, was investigated in a cohort of 250 chronic HD patients and who were undergoing regular dialysis three times per week were monitored for 1 yr. During that follow-up period, major cardiac events and all-cause deaths were prospectively recorded. At baseline, high plasma S-nitrosothiol levels (Ͼ2 M, corresponding to the top quartile of all measured values) were independently associated with pulse pressure in an adjusted multivariate analysis (odds ratio, 1.03; 95% confidence interval, 1.01 to 1.05; P ϭ 0.007). During the follow-up period, 36 patients died (16 as a result of cardiac causes) and 33 patients experienced major adverse cardiac events. In an adjusted Cox proportional-hazards model, high plasma S-nitrosothiol concentrations (i.e., the top quartile versus the three other quartiles) were an independent predictor of cardiac events (hazard ratio, 3.30; 95% confidence interval, 1.61 to 6.76; P ϭ 0.001) but not of all-cause death. Therefore, among chronic HD patients, markedly elevated plasma S-nitrosothiol levels are associated with pulse pressure and predict cardiovascular outcomes. These findings support the hypothesis that impaired S-nitrosothiol bioavailability in uremia is an important factor for the excessive cardiovascular risk among HD patients.Premature atherosclerosis is one of the primary causes of morbidity and death among patients with ESRD (1,2). Among several classic and nonclassic mechanisms conferring increased cardiovascular risk, impairment of nitric oxide (NO) bioavailability has emerged as a potentially important mechanism. Impaired NO-mediated, endothelium-dependent vasodilation, an early marker of atherosclerosis, has been observed among patients with predialysis chronic renal failure (3) and patients with ESRD (4,5). The impaired endothelium-dependent vasodilation could be linked to an absolute deficit of NO production. Indeed, increased levels of asymmetric dimethylarginine (ADMA), an active endogenous inhibitor of NO synthase, have been observed to be associated with the severity of atherosclerosis, independently of other vascular risk factors (6), and with concentric left ventricular hypertrophy and left ventricular dysfunction among patients with ESRD (7). Moreover, associations between ADMA levels and overall mortality or cardiovascular outcome rates were recently demonstrated among patients with ESRD (8).However, the ...

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Section: Discussioncontrasting

confidence: 87%

Increased Plasma S-Nitrosothiol Concentrations Predict Cardiovascular Outcomes among Patients with End-Stage Renal Disease

Massy¹,

Fumeron²,

Borderie³

et al. 2004

Journal of the American Society of Nephrology

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“…Because these groups did not measure and did not consider nitrite concentration, there is reasonable doubt about the value of these measurements (Tsikas, 2003;Tsikas and Frölich, 2003;. Furthermore both groups (i.e., Massy et al, 2003;Wlodek et al, 2003) have used the same method (i.e., Marzinzig et al, 1997) to measure S-nitrosothiols in plasma, but the S-nitrosothiol basal levels measured in their control groups differed almost by a factor of 20, namely 8.8 µM (Wlodek et al, 2003) and 0.45 µM (Massy et al, 2003). Regardless of these analytical problems and identified pitfalls, the same method has been used in a prospective study (Massy et al, 2004) that has revealed increased plasma S-nitrosothiol concentration to predict cardiovascular outcomes in end-stage renal disease patients (for discussion, see ; see also Section 11.3.2).…”

Section: Interference Of Nitrite and Nitrate In The Measurement Of S-mentioning

confidence: 98%

“…Application of such an assay (i.e., use of ammonium sulfamate at almost neutral pH value) to quantify S-nitrosothiols in human serum and cell culture media revealed S-nitrosothiol levels that were almost identical with those of nitrite (Marzinzig et al, 1997), strongly suggesting that this method is not specific for S-nitrosothiols but actually measures nitrite plus S-nitrosothiols. Nevertheless, this method has been applied by other groups (Massy et al, 2003;Wlodek et al, 2003), apparently without any modification of the original method (Marzinzig et al, 1997), to measure S-nitrosothiols in plasma of patients suffering from chronic renal diseases. Because these groups did not measure and did not consider nitrite concentration, there is reasonable doubt about the value of these measurements (Tsikas, 2003;Tsikas and Frölich, 2003;.…”

Section: Interference Of Nitrite and Nitrate In The Measurement Of S-mentioning

confidence: 99%

“…By evidence (Tsikas, 2003;Ng et al, 2004), elimination of nitrite by ammonium sulfamate requires acidic conditions. Therefore in all those studies where ammonium sulfamate was used under plasma-pH conditions and plasma nitrite concentrations were not determined or simply neglected (Marzinzig et al, 1997;Massy et al, 2003Massy et al, , 2004Wlodek et al, 2003), the values reported for plasma S-nitrosothiols and the conclusions made are questionable.…”

Section: S -Nitrosothiolsmentioning

confidence: 99%

“…Other studies (Massy et al, 2003(Massy et al, , 2004Wlodek et al, 2003) in which the same method of S-nitrosothiol analysis was used (i.e., Marzinzig et al, 1997) can be discussed from the same standpoint. Thus S-nitrosothiol plasma mean levels were measured to be 8.8 µM in healthy humans (Wlodek et al, 2003)-it should be noted that the same method revealed only 0.45 µM for plasma S-nitrosothiols in healthy humans (Marzinzig et al, 1997)-and 11.0 µM in patients with chronic renal failure, with corresponding nitrite + nitrate plasma levels being 120 µM and 135 µM, and plasma nitrite levels not being reported (Wlodek et al, 2003).…”

Section: S -Nitrosothiolsmentioning

confidence: 99%

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The highly diverse biological roles of nitric oxide (NO) in both physiological and pathophysiological processes have prompted great interest in the use of NO as a therapeutic agent in various biomedical applications. NO can exert either protective or deleterious effects depending on its concentration and the location where it is delivered or generated. This double-edged attribute, together with the short half-life of NO in biological systems, poses a major challenge to the realization of the full therapeutic potential of this molecule. Controlled release strategies show an admirable degree of precision with regards to the spatiotemporal dosing of NO but are disadvantaged by the finite NO deliverable payload. In turn, enzyme-prodrug therapy techniques afford enhanced deliverable payload but are troubled by the inherent low stability of natural enzymes, as well as the requirement to control pharmacokinetics for the exogenous prodrugs. The past decade has seen the advent of a new paradigm in controlled delivery of NO, namely localized bioconversion of the endogenous prodrugs of NO, specifically by enzyme mimics. These early developments are presented, successes of this strategy are highlighted, and possible future work on this avenue of research is critically discussed.

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Alteration in plasma levels of nonprotein sulfhydryl compounds and S-nitrosothiols in chronic renal failure patients

Cited by 18 publications

References 21 publications

Increased Plasma S-Nitrosothiol Concentrations Predict Cardiovascular Outcomes among Patients with End-Stage Renal Disease

Increased Plasma S-Nitrosothiol Concentrations Predict Cardiovascular Outcomes among Patients with End-Stage Renal Disease

Quantitative Determination of Free and Protein‐Associated 3‐Nitrotyrosine and S ‐Nitrosothiols in the Circulation by Mass Spectrometry and Other Methodologies: A Critical Review and Discussion from the Analytical and Review Point of View

Enzyme Mimics for the Catalytic Generation of Nitric Oxide from Endogenous Prodrugs

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