Incomplete Recovery from the Radiocontrast-Induced Dysregulated Cell Cycle, Adhesion, and Fibrogenesis in Renal Tubular Cells after Radiocontrast (Iohexol) Removal
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Published:2023-06-30
Issue:13
Volume:24
Page:10945
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Chen Hsing-Yu123ORCID, Wu Yi-Hong23, Wei Cheng-Yu1, Liao Zhi-Yao1, Wu Hsiao-Ting1, Chen Yung-Chang45, Pang Jong-Hwei S.16
Affiliation:
1. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan 2. Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan 33378, Taiwan 3. School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan 4. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan 5. Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan 33342, Taiwan 6. Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan 33342, Taiwan
Abstract
Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-β1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.
Funder
Chang Gung Memorial Hospital National Science and Technology Council Standard Food Corporation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference67 articles.
1. Contrast nephropathy;Murphy;J. Am. Soc. Nephrol.,2000 2. Understanding and preventing contrast-induced acute kidney injury;Fahling;Nat. Rev. Nephrol.,2017 3. Acute renal failure after coronary intervention: Incidence, risk factors, and relationship to mortality;McCullough;Am. J. Med.,1997 4. Contrast-Induced Nephropathy and Acute Renal Failure Following Emergent Cardiac Catheterization: Incidence, Risk Factors and Prognosis;Revista Española de Cardiología (Engl. Ed.),2007 5. Contrast-induced nephropathy: Definition, epidemiology, and patients at risk;Mehran;Kidney Int. Suppl.,2006
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