The Effect of Hydroxyethyl Starches (HES 130/0.42 and HES 200/0.5) on Activated Renal Tubular Epithelial Cells

Wittlinger, Moritz; Schläpfer, Martin; Conno, Elisena De; Z’graggen, Birgit Roth; Reyes, Livia; Booy, Christa; Schimmer, Ralph C.; Seifert, Burkhardt; Burmeister, Marc-Alexander; Spahn, Donat R.; Beck‐Schimmer, Beatrice

doi:10.1213/ane.0b013e3181c03c97

Cited by 12 publications

(7 citation statements)

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“…demonstrated that resuscitation using 8 mL/kg HES 200 prevents oxidative stress and nuclear factor-kappa B (NF-κB) activation [35]. HES 200 attenuates cell injury in inflammatory-stimulated tubular epithelial cells in vitro [31]. However, these results are not consistent with our observations.…”

Section: Discussioncontrasting

confidence: 85%

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Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin

et al. 2013

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IntroductionThis study compared the effects of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin on oxidative stress and the inflammatory response in a rodent hemorrhagic shock model.MethodsSodium pentobarbital-anesthetized adult male Wistar rats (200 g to 220 g) were subjected to a severe volume-controlled hemorrhage using arterial blood withdrawal (30 mL/kg to 33 mL/kg) and resuscitated with a colloid solution at the same volume as blood withdrawal (hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, or succinylated gelatin). Arterial blood gas parameters were monitored. Malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the liver, lungs, intestine, and brain were measured two hours after resuscitation. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 in the intestine were also measured.ResultsInfusions of hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, significantly reduced MDA levels and MPO activity in the liver, intestine, lungs and brain, and it also inhibited the production of TNF-α in the intestine two hours after resuscitation. However, no significant difference between hydroxyethyl starch 200/0.5 and succinylated gelatin was observed.ConclusionsHydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, treatment after hemorrhagic shock ameliorated oxidative stress and the inflammatory response in this rat model. No significant differences were observed after hydroxyethyl starch 200/0.5 or succinylated gelatin administration at doses of approximately 33 mL/kg.

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Section: Discussioncontrasting

confidence: 85%

“…HES 200 exhibits anti-inflammatory effects in vivo and in vitro [31-34]. In an HS model, a 20 mL/kg HES 200 infusion inhibits the inflammatory response following HS/R compared to GEL [17].…”

Section: Discussionmentioning

confidence: 99%

Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin

et al. 2013

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“…It has been shown that under certain disease models that kidney cells produce TNF-α [51] and MCP-1 [52,53]. Here we show that exposure to these particular nanomaterials even at very high (in some cases cytotoxic) doses are not sufficient for MCP-1 or TNF-α secretion from the cells.…”

Section: Discussionmentioning

confidence: 49%

An in vitroassessment of panel of engineered nanomaterials using a human renal cell line: cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity

et al. 2013

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BackgroundIt has been shown that nanomaterials (NMs) are able to translocate to secondary tissues one of the important being the kidneys. Oxidative stress has been implicated as a possible mechanism for NM toxicity, hence effects on the human renal proximal tubule epithelial cells (HK-2) treated with a panel of engineered nanomaterials (NMs) consisting of two zinc oxide particles (ZnO - coated - NM 110 and uncoated - NM 111), two multi walled carbon nanotubes (MWCNT) (NM 400 and NM 402), one silver (NM 300) and five TiO2 NMs (NM 101, NRCWE 001, 002, 003 and 004) were evaluated.MethodsIn order to assess the toxicological impact of the engineered NMs on HK-2 cells - WST-1 cytotoxicity assay, FACSArray, HE oxidation and the comet assays were utilised. For statistical analysis, the experimental values were compared to their corresponding controls using an ANOVA with Tukey’s multiple comparison.ResultsWe found the two ZnO NMs (24 hr LC50 – 2.5 μg/cm2) and silver NM (24 hr LC50 – 10 μg/cm2) were highly cytotoxic to the cells. The LC50 was not attained in the presence of any of the other engineered nanomaterials (up to 80 μg/cm2). All nanomaterials significantly increased IL8 and IL6 production. Meanwhile no significant change in TNF-α or MCP-1 was detectable. The most notable increase in ROS was noted following treatment with the Ag and the two ZnO NMs. Finally, genotoxicity was measured at sub-lethal concentrations. We found a small but significant increase in DNA damage following exposure to seven of the ten NMs investigated (NM 111, NRCWE 001 and NRCWE 003 being the exception) with this increase being most visible following exposure to Ag and the positively charged TiO2.ConclusionsWhile the NMs could be categorised as low and highly cytotoxic, sub-lethal effects such as cytokine production and genotoxicity were observed with some of the low toxicity materials.

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“…A modulation of the inflammatory response caused by the different type of fluids has been suggested to play a key role. In a previous study, we demonstrated in an in vitro model of human proximal tubular epithelial cells (HK-2) that HES products modulate cell injury upon inflammatory stimulation with tumor necrosis factor α (TNFα) with a more pronounced effect for HES 200/0.5 than for HES 130/0.42 [13]. Additionally, since the introduction of “plasma-adapted” fluids during the recent years the discussion on optimal fluid resucitation has been extended to the question of the buffering agent.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Early Inflammatory Response by Different Balanced and Non-Balanced Colloids and Crystalloids in a Rodent Model of Endotoxemia

et al. 2014

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The use of hydroxyethyl starch (HES) in sepsis has been shown to increase mortality and acute kidney injury. However, the knowledge of the exact mechanism by which several fluids, especially starch preparations may impair end-organ function particularly in the kidney, is still missing. The aim of this study was to measure the influence of different crystalloid and colloid fluid compositions on the inflammatory response in the kidney, the liver and the lung using a rodent model of acute endotoxemia. Rats were anesthetized and mechanically ventilated. Lipopolysaccharide (5 mg/kg) was administered intravenously. After one hour crystalloids [lactate-buffered (RLac) or acetate-buffered (RAc)] were infused i.v. (30 ml/kg) in all groups. At 2 hours rats either received different crystalloids (75 ml/kg of RLac or RAc) or colloids (25 ml/kg of HES in saline or HES in RAc or gelatin in saline). Expression of messenger RNA for cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemotactic protein-1 (MCP-1), necrosis factor α (TNFα) and intercellular adhesion molecule 1 (ICAM-1) was assessed in kidney, liver and lung tissue by real-time PCR after 4 hours. The use of acetate-buffered solutions was associated with a significantly higher expression of CINC-1 and TNFα mRNA in the liver, in the kidney and in the lung. Only marginal effects of gelatin and hydroxyethyl starch on mRNA expression of inflammatory mediators were observed. The study provides evidence that the type of buffering agent of different colloidal and crystalloid solutions might be a crucial factor determining the extent of early end-organ inflammatory response in sepsis.

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The Effect of Hydroxyethyl Starches (HES 130/0.42 and HES 200/0.5) on Activated Renal Tubular Epithelial Cells

Abstract: This in vitro study shows that both HES products modulate cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200/0.5 group than for HES 130/0.42, suggesting a possible biological difference between the HES types.

Cited by 12 publications

References 39 publications

Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin

Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin

An in vitroassessment of panel of engineered nanomaterials using a human renal cell line: cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity

Modulation of Early Inflammatory Response by Different Balanced and Non-Balanced Colloids and Crystalloids in a Rodent Model of Endotoxemia

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