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. 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, 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. In addition, the serum and intracellular protein levels of HMGB1 were analyzed. 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. 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.

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

Scientific Reports ◽

10.1038/s41598-021-94928-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hyewon Oh ◽

Arom Choi ◽

Nieun Seo ◽

Joon Seok Lim ◽

Je Sung You ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Contrast Media ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Kidney Tissue ◽

Kidney Injury ◽

Enzyme Linked Immunosorbent Assay ◽

Post Contrast ◽

Pro Inflammatory Cytokines

AbstractPost 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.

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Radiology departmental policy compliance with Swedish guidelines regarding post-contrast acute kidney injury for examinations with iodinated contrast media

Radiography ◽

10.1016/j.radi.2021.04.009 ◽

2021 ◽

Author(s):

A. Bjällmark ◽

M. Bazzi ◽

M. Karlsson ◽

E. Krakys ◽

J. Kihlberg

Keyword(s):

Acute Kidney Injury ◽

Contrast Media ◽

Kidney Injury ◽

Iodinated Contrast Media ◽

Policy Compliance ◽

Post Contrast ◽

Iodinated Contrast

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Docosahexaenoic Acid-Acylated Astaxanthin Esters Exhibit Superior Renal Protective Effect to Recombination of Astaxanthin with DHA via Alleviating Oxidative Stress Coupled with Apoptosis in Vancomycin-Treated Mice with Nephrotoxicity

Marine Drugs ◽

10.3390/md19090499 ◽

2021 ◽

Vol 19 (9) ◽

pp. 499

Author(s):

Hao-Hao Shi ◽

Ying Guo ◽

Li-Pin Chen ◽

Cheng-Cheng Wang ◽

Qing-Rong Huang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Fatty Acid ◽

Docosahexaenoic Acid ◽

Kidney Injury ◽

Clinical Problem ◽

Kidney Dysfunction ◽

Serum Biochemical ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

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Iodinated contrast medium: Is there a re(n)al problem? A clinical vignette-based review

Critical Care ◽

10.1186/s13054-020-03365-9 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Karim Lakhal ◽

Stephan Ehrmann ◽

Vincent Robert-Edan

Keyword(s):

Acute Kidney Injury ◽

Contrast Media ◽

Kidney Injury ◽

Case Vignette ◽

Iodinated Contrast Media ◽

Iodinated Contrast Medium ◽

Iodinated Contrast ◽

Prophylactic Measures ◽

Indirect Consequence ◽

Toxic Potential

Abstract As we were taught, for decades, that iodinated contrast-induced acute kidney injury should be dreaded, considerable efforts were made to find out effective measures in mitigating the renal risk of iodinated contrast media. Imaging procedures were frequently either downgraded (unenhanced imaging) or deferred as clinicians felt that the renal risk pertaining to contrast administration outweighed the benefits of an enhanced imaging. However, could we have missed the point? Among the abundant literature about iodinated contrast-associated acute kidney injury, recent meaningful advances may help sort out facts from false beliefs. Hence, there is increasing evidence that the nephrotoxicity directly attributable to modern iodinated CM has been exaggerated. Failure to demonstrate a clear benefit from most of the tested prophylactic measures might be an indirect consequence. However, the toxic potential of iodinated contrast media is well established experimentally and should not be overlooked completely when making clinical decisions. We herein review these advances in disease and pathophysiologic understanding and the associated clinical crossroads through a typical case vignette in the critical care setting.

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