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Ergin B, Guerci P, Zafrani L, et al. Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia. Intensive Care Med Exp. 2016;4(1):29doi: 10.1186/s40635-016-0106-1.
Ergin, B., Guerci, P., Zafrani, L., Nocken, F., Kandil, A., Gurel-Gurevin, E., Demirci-Tansel, C., & Ince, C. (2016). Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia. Intensive care medicine experimental, 4(1), 29. https://doi.org/10.1186/s40635-016-0106-1
Ergin, Bulent, et al. "Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia." Intensive care medicine experimental vol. 4,1 (2016): 29. doi: https://doi.org/10.1186/s40635-016-0106-1
Ergin B, Guerci P, Zafrani L, Nocken F, Kandil A, Gurel-Gurevin E, Demirci-Tansel C, Ince C. Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia. Intensive Care Med Exp. 2016 Dec;4(1):29. doi: 10.1186/s40635-016-0106-1. Epub 2016 Sep 26. PMID: 27671340; PMCID: PMC5037099.
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Intensive Care Med Exp. 2016 Dec;4(1):29. doi: 10.1186/s40635-016-0106-1. Epub 2016 Sep 26.

Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia.

Intensive care medicine experimental

Bulent Ergin, Philippe Guerci, Lara Zafrani, Frank Nocken, Asli Kandil, Ebru Gurel-Gurevin, Cihan Demirci-Tansel, Can Ince

Affiliations

  1. Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].
  2. Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. [email protected].
  3. Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
  4. University of Lorraine, Vandoeuvre-Lès-Nancy, France.
  5. Divisional Medical & Clinical Affairs Generics & Standard Solutions, Volume Therapy, Fresenius Kabi Deutschland GmbH, Berlin, Germany.
  6. Department of Biology, Faculty of Science, University of Istanbul, Istanbul, Turkey.
  7. Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

PMID: 27671340 PMCID: PMC5037099 DOI: 10.1186/s40635-016-0106-1

Abstract

BACKGROUND: Modulation of inflammation and oxidative stress appears to limit sepsis-induced damage in experimental models. The kidney is one of the most sensitive organs to injury during septic shock. In this study, we evaluated the effect of N-acetylcysteine (NAC) administration in conjunction with fluid resuscitation on renal oxygenation and function. We hypothesized that reducing inflammation would improve the microcirculatory oxygenation in the kidney and limit the onset of acute kidney injury (AKI).

METHODS: Rats were randomized into five groups (n = 8 per group): (1) control group, (2) control + NAC, (3) endotoxemic shock with lipopolysaccharide (LPS) without fluids, (4) LPS + fluid resuscitation, and (5) LPS + fluid resuscitation + NAC (150 mg/kg/h). Fluid resuscitation was initiated at 120 min and maintained at fixed volume for 2 h with hydroxyethyl starch (HES 130/0.4) dissolved in acetate-balanced Ringer's solution (Volulyte) with or without supplementation with NAC (150 mg/kg/h). Oxygen tension in the renal cortex (CμPO2), outer medulla (MμPO2), and renal vein was measured using phosphorimetry. Biomarkers of renal injury, inflammation, and oxidative stress were assessed in kidney tissues.

RESULTS: Fluid resuscitation significantly improved the systemic and renal macrohemodynamic parameters after LPS. However, the addition of NAC further improved cortical renal oxygenation, oxygen delivery, and oxygen consumption (p < 0.05). NAC supplementation dampened the accumulation of NGAL or L-FABP, hyaluronic acid, and nitric oxide in kidney tissue (p < 0.01).

CONCLUSION: The addition of NAC to fluid resuscitation may improve renal oxygenation and attenuate microvascular dysfunction and AKI. Decreases in renal NO and hyaluronic acid levels may be involved in this beneficial effect. A therapeutic strategy combining initial fluid resuscitation with antioxidant therapies may prevent sepsis-induced AKI.

Keywords: Acute kidney injury; Inflammation; Kidney oxygenation; N-acetylcysteine; Sepsis

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