APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells

Li, Yimin; Huang, Jin; He, Shenghu; Zhang, Lu; Zhang, Jing; Li, Xiangyu; Yang, Zhijian; Hoffman, Robert M.; Wu, Qinghua

doi:10.21873/anticanres.13993

Cited by 11 publications

(6 citation statements)

References 22 publications

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“…These results suggested that iopromide-induced HEK 293 apoptosis is mediated through the induction of autophagy Iopromide elicited ROS production and suppressed the AKT signaling pathway. A previous study demonstrated that ROS production was induced by iodinated contrast media (40). Indeed, treatment of HEK 293 cells with 50 mgI/ml iopromide resulted in a 165% increase in ROS production (Figure 9A and B).…”

Section: Iopromide Triggers Autophagy To Protect Cells From Apoptosismentioning

confidence: 63%

High Concentration of Iopromide Induces Apoptosis and Autophagy in Human Embryonic Kidney CellsviaActivating a ROS-dependent Cellular Stress Pathway

Tsai¹,

Yang

Tsai

et al. 2021

In Vivo

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Background/Aim: The use of iodinated contrast media may impair renal function. However, no report has addressed the nephrotoxicity of high doses of iodinated contrast media in normal kidney cells and its associated molecular mechanisms. Materials and Methods: Cell proliferation was assessed using the MTT assay. Cell death was evaluated through examining the morphological changes and TUNEL assay. Autophagy was detected through acridine orange staining and lysotracker staining. Reactive oxygen species production and AKT kinase activity were examined. Results: Iopromide induced cell death and triggered apoptosis and autophagy in HEK 293 cells. Cell viability was significantly restored in the presence of a pan-caspase inhibitor or a ROS scavenger, N-acetyl-L-cysteine. AKT kinase activity was found to be reduced in iopromide-treated HEK 293 cells. Conclusion: High concentrations of iopromide induce cell damage, apoptosis, and autophagy through down-regulating AKT and ROS-activated cellular stress pathways in HEK 293 cells.Roentgen discovered X-rays at the end of 19 th century, which was followed by the introduction of iodine-containing contrast media (ICCM) at the beginning of the 20 th century that opened up a new field of research in medical science (1-4). Iodine-containing contrast agents are administrated into the human body through veins and used for radiological diagnostic examinations of the urinary system, heart, cerebrospinal system, and blood vessels in various parts of the body. ICCM enhances the contrast between normal tissue and lesions, provides information on the morphologic features of the lesions, and improves the sensitivity of the examination and the accuracy of diagnosis. The imaging enhancement effect of the contrast agent makes many tissues and cell lesions visible (5-8). The main pharmacological mechanism is that the iodine molecules in the iodinecontaining contrast agent absorb X-ray energy, which makes the iodine molecules exert a special X-ray shielding effect. Therefore, a white high-density image appears on the X-ray 3221 This article is freely accessible online.

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Section: Iopromide Triggers Autophagy To Protect Cells From Apoptosismentioning

confidence: 63%

High Concentration of Iopromide Induces Apoptosis and Autophagy in Human Embryonic Kidney CellsviaActivating a ROS-dependent Cellular Stress Pathway

Tsai¹,

Yang

Tsai

et al. 2021

In Vivo

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“…Attempts to identify the endogenous levels of these peptides proved difficult owing to their physicochemical properties, which predispose ELA peptides to oxidation and poor chromatographic peaks. Given the beneficial effects of ELA signalling in various disease states including renal [ 9 , 37 , 38 , 8 , 32 , 33 ] and cardiovascular diseases [ 6 , 39 ], the long half-life observed here may suggest that ELA peptides could be a potential therapeutic option for managing these conditions.…”

Section: Discussionmentioning

confidence: 95%

In vitro metabolism of synthetic Elabela/Toddler (ELA-32) peptide in human plasma and kidney homogenates analyzed with mass spectrometry and validation of endogenous peptide quantification in tissues by ELISA

et al. 2021

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Highlights Elabela/Toddler (ELA) is the second endogenous ligand of the apelin receptor identified in zebrafish. Mature ELA was predicted to be cleaved into [Pyr 1 ]ELA-32, ELA-21 and ELA-11, based on the presence of dibasic amino acid residues. We have shown that the half-life of [Pyr 1 ]ELA-32 was ∼50 min in human plasma and <1 min when incubated with human kidney. After incubation of [Pyr 1 ]ELA-32 in human plasma, ELA-16 and ELA-11, but not ELA-21, were identified as major metabolites. Our study provides information that may lead to the design of biologically stable ELA peptide analogues.

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“…In this study, we focused on the specific group of CKD patients, specifically at stages 3 and 4, who received only iodixanol as a contrast media. Previous studies in rats and in renal tubular epithelial cells reported that iodixanol caused mitochondrial dysfunction 19,20 . However, the roles of mitochondria in CI‐AKI in CKD patients are still unknown.…”

Section: Discussionmentioning

confidence: 99%

Circulating mitochondrial dysfunction as an early biomarker for contrast media‐induced acute kidney injury in chronic kidney disease patients

Kusirisin

Apaijai

Noppakun

et al. 2023

J Cellular Molecular Medi

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Contrast‐induced acute kidney injury (CI‐AKI) is the common hospitalized acute kidney injury (AKI). However, the diagnosis by serum creatinine might not be early enough. Currently, the roles of circulating mitochondria in CI‐AKI are still unclear. Since early detection is crucial for treatment, the association between circulating mitochondrial function and CI‐AKI was tested as a potential biomarker for detection of CI‐AKI. Twenty patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) were enrolled. Blood and urine samples were obtained at the time of PCI, and 6, 24, 48 and 72 h after PCI. Plasma and urine neutrophil gelatinase‐associated lipocalin (NGAL) were measured. Oxidative stress, inflammation, mitochondrial function, mitochondrial dynamics and cell death were determined from peripheral blood mononuclear cells. Forty percent of patients developed AKI. Plasma NGAL levels increased after 24 h after receiving contrast media. Cellular and mitochondrial oxidative stress, mitochondrial dysfunction and decreased mitochondrial fusion occurred at 6 h following contrast media exposure. Subgroup of AKI had higher %necroptosis cells and TNF‐α mRNA expression than subgroup without AKI. Collectively, circulating mitochondrial dysfunction could be an early predictive biomarker for CI‐AKI in CKD patients receiving contrast media. These findings provide novel strategies to prevent CI‐AKI according to its pathophysiology.

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APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells

Cited by 11 publications

References 22 publications

High Concentration of Iopromide Induces Apoptosis and Autophagy in Human Embryonic Kidney CellsviaActivating a ROS-dependent Cellular Stress Pathway

High Concentration of Iopromide Induces Apoptosis and Autophagy in Human Embryonic Kidney CellsviaActivating a ROS-dependent Cellular Stress Pathway

In vitro metabolism of synthetic Elabela/Toddler (ELA-32) peptide in human plasma and kidney homogenates analyzed with mass spectrometry and validation of endogenous peptide quantification in tissues by ELISA

Circulating mitochondrial dysfunction as an early biomarker for contrast media‐induced acute kidney injury in chronic kidney disease patients

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