Intravascular Radiocontrast Iodixanol Increases Permeability of Proximal Tubule Epithelium

Yao, Luyu; Kolluru, Gopi K.; Kevil, Christopher G.; Zhang, Wayne W.

doi:10.1177/1538574413503560

Cited by 6 publications

(9 citation statements)

References 20 publications

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“…Specifically, cell viability following exposure with CM at concentrations of 150, 225, and 300 mg I 2 /mL was 69.5%, 37.3%, and 4.8%. Such findings have been demonstrated on previously published HK2 models using similar MTT methods to assess cell viability [10,11,13]. Peng et al similarly identified a dose-dependent response with cell viability decreasing progressively from 100% to 12% following exposures of 80 mg I/ml over 16 hours [11].…”

Section: Zinc Preconditioning Has Protective Effect On Cell Viabilitysupporting

confidence: 58%

“…e cytotoxic effects of contrast on renal cells may have been effectively assessed in in vitro models. Specifically, several groups have outlined the reno-protective effects of various agents on HK-2 cell lines [7][8][9][10][11][12][13][14]. e aim of the current study is to assess the outcomes of zinc pre-conditioning on HK-2 renal cell lines following contrast administration.…”

Section: Introductionmentioning

confidence: 99%

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Zinc Preconditioning Provides Cytoprotection following Iodinated Contrast Media Exposure in In Vitro Models

Perera

Ischia

Bolton

et al. 2021

Contrast Media & Molecular Imaging

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Introduction & Objectives. Contrast media (CM) causes renal injury through both direct cellular injury (cytotoxicity) and regional vascular changes (renal hypoxia) mediated by reactive oxygen species (ROS). Zinc may be able to provide protection against CM-induced cytotoxicity due to its indirect antioxidant properties and subsequent effect on ROS. We aimed to determine the protective role of zinc preconditioning against contrast-induced renal injury in vitro. Methods. Normal human proximal renal kidney cells (HK-2) were preconditioned with either increasing doses of ZnCl2 or control. Following this preconditioning, cells were exposed to increasing concentrations of Iohexol 300 mg I2/ml for four hours. Key outcome measures included cell survival (MTT colorimetric assay) and ROS generation (H2DCFDA fluorescence assay). Results. Contrast media induced a dose-dependent reduction in survival of HK-2 cells. Compared to control, contrast media at 150, 225, and 300 mg I2/ml resulted in 69.5% (SD 8.8%), 37.3% (SD 4.8%), and 4.8% (SD 6.6%) cell survival, respectively ( p < 0.001 ). Preconditioning with 37.5 μM and 50 μM ZnCl2 increased cell survival by 173% (SD 27.8%) ( p < 0.001 ) and 219% (SD 32.2%) ( p < 0.001 ), respectively, compared to control preconditioning. Zinc preconditioning resulted in a reduction of ROS generation. Zinc pre-conditioning with 37.5 μM μM ZnCl2 reduced ROS generation by 46% ( p < 0.001 ) compared to control pre-conditioning. Conclusions. Zinc preconditioning reduces oxidative stress following exposure to radiographic contrast media which in turn results in increased survival of renal cells. Translation of this in vitro finding in animal models will lay the foundation for future use of zinc preconditioning against contrast induced nephropathy.

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Section: Zinc Preconditioning Has Protective Effect On Cell Viabilitysupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Zinc Preconditioning Provides Cytoprotection following Iodinated Contrast Media Exposure in In Vitro Models

Perera

Ischia

Bolton

et al. 2021

Contrast Media & Molecular Imaging

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“…Solute permeability was tested using 6.5 mm transwell inserts with 0.4 µm pore size (07–200-154, Fisher Scientific) as previously described [42] . Transwell inserts were coated with fibronectin.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen sulfide metabolism regulates endothelial solute barrier function

et al. 2016

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Hydrogen sulfide (H2S) is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs) were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE), a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

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“…Decreasing cell proliferation by CellTiter 96 assay. [ 53 ] LLC-PK1 (Pig renal tubular epithelial cells) Iodixanol (Visipaque) 18.75-75 mgI/ ml 24 h 1. Decreasing cell proliferation by BrdU assay 2.…”

Section: In-vitro Studies On Contrast-induced Nephropathy (Cmentioning

confidence: 99%

The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM)

et al. 2018

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Iodinated contrast media (iodinated CM) have increased ability to absorb x-rays and to visualize structures that normally are impossible to observe in a radiological examination. The use of iodinated CM may destory renal function, commonly known as contrast-induced nephropathy (CIN), which can result in acute renal failure (ARF). This review article mainly focuses on the following areas: (1) classifications of iodinated CM: ionic or non-ionic, high-osmolarity contrast media (HOCM), low-osmolarity contrast media (LOCM) and iso-osmolarity contrast media (IOCM); (2) an introduction to the physical and chemical properties of the non-ionic iodinated CM; (3) the management of anaphylactic reaction by iodinated CM; (4) a suggested single injection of adult doses and maximum dose for non-ionic iodinated CM; (5) the molecular mechanism of contrast-induced nephropathy (CIN); (6) In vitro studies on iodinated CM. Based on above information, this review article provide an insight for understanding the drug safety of iodinated CM.

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Intravascular Radiocontrast Iodixanol Increases Permeability of Proximal Tubule Epithelium

Abstract: Our in vitro data do not support the hypothesis that direct kidney cell death from Iodixanol is a major mechanism of contrast-induced nephropathy (CIN). However, increased permeability of proximal tubule epithelium caused by Iodixanol may play an important role in CIN.

Cited by 6 publications

References 20 publications

Zinc Preconditioning Provides Cytoprotection following Iodinated Contrast Media Exposure in In Vitro Models

Zinc Preconditioning Provides Cytoprotection following Iodinated Contrast Media Exposure in In Vitro Models

Hydrogen sulfide metabolism regulates endothelial solute barrier function

The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM)

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