Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury

Abstract Post contrast-acute kidney injury (PC-AKI) is defined as the deterioration of renal function after administration of iodinated contrast media. HMGB1 is known to play an important role in the development of acute kidney injury. The purpose of this study was to investigate the association bet...

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Autores principales:	Hyewon Oh, Arom Choi, Nieun Seo, Joon Seok Lim, Je Sung You, Yong Eun Chung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d3b8a592b6d846bbb0cb4068c4dd6849
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spelling	oai:doaj.org-article:d3b8a592b6d846bbb0cb4068c4dd68492021-12-02T16:35:36ZProtective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury10.1038/s41598-021-94928-52045-2322https://doaj.org/article/d3b8a592b6d846bbb0cb4068c4dd68492021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94928-5https://doaj.org/toc/2045-2322Abstract Post contrast-acute kidney injury (PC-AKI) is defined as the deterioration of renal function after administration of iodinated contrast media. HMGB1 is known to play an important role in the development of acute kidney injury. The purpose of this study was to investigate the association between HMGB1 and PC-AKI and the protective effect of glycyrrhizin, a direct inhibitor of HMGB1, in rats. Rats were divided into three groups: control, PC-AKI and PC-AKI with glycyrrhizin. Oxidative stress was measured with MDA levels and H2DCFDA fluorescence intensity. The mRNA expressions of pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) and kidney injury markers (KIM-1, NGAL and IL-18) were assessed using RT-PCR and ELISA in kidney tissue. In addition, the serum and intracellular protein levels of HMGB1were analyzed with the enzyme-linked immunosorbent assay (ELISA) and western blotting. Histologic changes were assessed with H&E staining using the transmission electron microscope (TEM). Moreover, serum creatinine (SCr), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) levels were assessed. Oxidative stress, pro-inflammatory cytokines, kidney injury markers and LDH were significantly higher in PC-AKI compared to the controls, but were lower in PC-AKI with glycyrrhizin. Intracellular and serum HMGB1 levels significantly increased after contrast media exposure, whereas they markedly decreased after glycyrrhizin pretreatment. SCr and BUN also decreased in PC-AKI with glycyrrhizin compared to PC-AKI. In PC-AKI, we could frequently observe tubular dilatation with H&E staining and cytoplasmic vacuoles on TEM, whereas these findings were attenuated in PC-AKI with glycyrrhizin. Our findings indicate that HMGB1 plays an important role in the development of PC-AKI and that glycyrrhizin has a protective effect against renal injury and dysfunction by inhibiting HMGB1 and reducing oxidative stress.Hyewon OhArom ChoiNieun SeoJoon Seok LimJe Sung YouYong Eun ChungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyewon Oh Arom Choi Nieun Seo Joon Seok Lim Je Sung You Yong Eun Chung Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury
description	Abstract Post contrast-acute kidney injury (PC-AKI) is defined as the deterioration of renal function after administration of iodinated contrast media. HMGB1 is known to play an important role in the development of acute kidney injury. The purpose of this study was to investigate the association between HMGB1 and PC-AKI and the protective effect of glycyrrhizin, a direct inhibitor of HMGB1, in rats. Rats were divided into three groups: control, PC-AKI and PC-AKI with glycyrrhizin. Oxidative stress was measured with MDA levels and H2DCFDA fluorescence intensity. The mRNA expressions of pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) and kidney injury markers (KIM-1, NGAL and IL-18) were assessed using RT-PCR and ELISA in kidney tissue. In addition, the serum and intracellular protein levels of HMGB1were analyzed with the enzyme-linked immunosorbent assay (ELISA) and western blotting. Histologic changes were assessed with H&E staining using the transmission electron microscope (TEM). Moreover, serum creatinine (SCr), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) levels were assessed. Oxidative stress, pro-inflammatory cytokines, kidney injury markers and LDH were significantly higher in PC-AKI compared to the controls, but were lower in PC-AKI with glycyrrhizin. Intracellular and serum HMGB1 levels significantly increased after contrast media exposure, whereas they markedly decreased after glycyrrhizin pretreatment. SCr and BUN also decreased in PC-AKI with glycyrrhizin compared to PC-AKI. In PC-AKI, we could frequently observe tubular dilatation with H&E staining and cytoplasmic vacuoles on TEM, whereas these findings were attenuated in PC-AKI with glycyrrhizin. Our findings indicate that HMGB1 plays an important role in the development of PC-AKI and that glycyrrhizin has a protective effect against renal injury and dysfunction by inhibiting HMGB1 and reducing oxidative stress.
format	article
author	Hyewon Oh Arom Choi Nieun Seo Joon Seok Lim Je Sung You Yong Eun Chung
author_facet	Hyewon Oh Arom Choi Nieun Seo Joon Seok Lim Je Sung You Yong Eun Chung
author_sort	Hyewon Oh
title	Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury
title_short	Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury
title_full	Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury
title_fullStr	Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury
title_full_unstemmed	Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury
title_sort	protective effect of glycyrrhizin, a direct hmgb1 inhibitor, on post-contrast acute kidney injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d3b8a592b6d846bbb0cb4068c4dd6849
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Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury

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