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Letter to the Editor| Volume 177, ISSUE 1, P30-33, November 15, 2014

N-Acetylcysteine (NAC) inhibits renal nitrite and nitrate reabsorption in healthy subjects and in patients undergoing cardiac surgery: Risk of nitric oxide (NO) bioavailability loss by NAC?

Published:September 27, 2014DOI:https://doi.org/10.1016/j.ijcard.2014.09.109
      N-Acetylcysteine (NAC) is used intravenously (i.v.) at high doses for the prevention of acute kidney injury after cardiac surgery [
      • Sisillo E.
      • Marenzi G.
      N-Acetylcysteine for the prevention of acute kidney injury after cardiac surgery.
      ] and in contrast-induced nephropathy (CIN) [
      • Golshahi J.
      • Nasri H.
      • Gharipour M.
      Contrast-induced nephropathy; a literature review.
      ]. Although the underlying mechanisms are not yet fully understood, altered nitric oxide (NO) and prostaglandin (PG) synthesis and elevated oxidative stress are assumed to play a crucial role, and NAC is currently considered as one of the best choices to prevent CIN in high-risk groups [
      • Golshahi J.
      • Nasri H.
      • Gharipour M.
      Contrast-induced nephropathy; a literature review.
      ]. Yet, a systematic meta-analysis of randomized controlled trials showed that prophylactic perioperative NAC in cardiac surgery does not reduce acute renal injury, haemodialysis, or death [
      • Adabag A.S.
      • Ishani A.
      • Bloomfield H.E.
      • Ngo A.K.
      • Wilt T.J.
      Efficacy of N-acetylcysteine in preventing renal injury after heart surgery: a systematic review of randomized trials.
      ]. We reasoned that NAC and its derivatives cysteine (Cys) and glutathione (GSH) may exert effects primarily not related to their intrinsic antioxidant activity. The aim of the present work was to investigate the acute effects of NAC in patients undergoing cardiac surgery and in healthy subjects on NO, PGE2, and oxidative stress. These studies are described in detail below. Whole body NO synthesis was estimated by measuring the urinary excretion of the NO metabolites nitrite and nitrate [
      • Tsikas D.
      • Gutzki F.M.
      • Stichtenoth D.O.
      Circulating and excretory nitrite and nitrate as indicators of nitric oxide synthesis in humans: methods of analysis.
      ]. Renal synthesis of the cyclooxygenase (COX)-dependent PGE2 was measured by analysing PGE2 in urine [
      • Stichtenoth D.O.
      • Marhauer V.
      • Tsikas D.
      • Gutzki F.M.
      • Frölich J.C.
      Effects of specific COX-2-inhibition on renin release and renal and systemic prostanoid synthesis in healthy volunteers.
      ]. Whole body oxidative stress was assessed by measuring the F2-isoprostane 15(S)-8-iso-PGF in urine samples [
      • Schwedhelm E.
      • Benndorf R.A.
      • Böger R.H.
      • Tsikas D.
      Mass spectrometric analysis of F2-isoprostanes: markers and mediators in human disease.
      ]. Urinary excretion of these biomarkers was corrected for urinary creatinine excretion.

      Keywords

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