Abstract
BackgroundModulation 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).MethodsRats 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.ResultsFluid 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).ConclusionThe 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.
Highlights
Modulation of inflammation and oxidative stress appears to limit sepsis-induced damage in experimental models
After LPS, the addition of NAC to the fluid did not result in improved hemodynamic parameters compared to fluid resuscitation alone
In the present study, we found that fluid supplemented with NAC improved cortical renal oxygenation, oxygen delivery, and oxygen consumption compared to the LPS group
Summary
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. Fluid resuscitation may help resolve some of these issues and lead to the activation of oxidative pathways in itself, resulting in a heterogeneous distribution of blood flow and tissue oxygenation, especially in the renal cortex [5, 6]. Because reactive oxygen species (ROS) participate in the pathophysiology of endotoxemic shock, it has been suggested that moderating the oxidative stress and inflammatory reaction would translate into improving the microcirculation and oxygenation of the tissues. The experimental literature is full of studies of drugs that target and are effective at dampening inflammation and oxidative stress. Acute kidney injury (AKI) and acute lung injury are common complications of sepsis, and the development of either increases mortality probably because these organs are more sensitive to inflammation and oxidative stress insults.
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