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

Oh, Hung Kun; Choi, Arom; Seo, Nieun; Lim, Joon Seok; You, Je Sung; Chung, Yong Eun

doi:10.1038/s41598-021-94928-5

Cited by 22 publications

(10 citation statements)

References 34 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These ndings are consistent with EtOH-induced release of HMGB1 and proin ammatory gene induction contributing to the loss of ChAT + IR BFCNs, but not neuronal death. We next determined whether HMGB1 contributes to the EtOH-induced loss of ChAT + IR BFCNs by applying the direct HMGB1 inhibitor glycyrrhizin 33 to FSC media during EtOH treatment. Consistent with our earlier ndings, EtOH caused a 41% (± 6%) reduction of ChAT + IR BFCNs, an effect that was blocked in EtOH-treated FSCs by glycyrrhizin (Fig.…”

Section: Resultsmentioning

confidence: 99%

HMGB1 Neuroimmune Signaling and REST-G9a Gene Repression Contribute to Ethanol-induced Reversible Suppression of the Cholinergic Neuron Phenotype

Vetreno

Fisher²,

Qin³

et al. 2023

Preprint

View full text Add to dashboard Cite

Adolescent binge drinking increases Toll-like receptor 4 (TLR4), receptor for advanced glycation end products (RAGE), the endogenous TLR4/RAGE agonist high-mobility group box 1 (HMGB1), and proinflammatory neuroimmune signaling in the adult basal forebrain in association with persistent reductions of basal forebrain cholinergic neurons (BFCNs). In vivo preclinical adolescent intermittent ethanol (AIE) studies find anti-inflammatory interventions post-AIE reverse the HMGB1-TLR4/RAGE neuroimmune signaling and loss of BFCNs in adulthood, suggesting proinflammatory signaling causes epigenetic repression of the cholinergic phenotype. Reversible loss of BFCN phenotype in vivo is linked to increased repressive histone 3 lysine 9 dimethylation (H3K9me2) occupancy at cholinergic gene promoters, and HMGB1-TLR4/RAGE proinflammatory signaling is linked to epigenetic repression of the cholinergic phenotype. Using an ex vivo basal forebrain slice culture (FSC) model, we report EtOH recapitulates the in vivo AIE-induced loss of ChAT + IR BFCNs, somal shrinkage of the remaining ChAT + neurons, and reduction of BFCN phenotype genes. Ex vivo targeted inhibition of EtOH-induced proinflammatory HMGB1 blocked ChAT + IR loss while disulfide HMBG1-TLR4 and fully reduced HMGB1-RAGE signaling decreased ChAT + IR BFCNs. EtOH increased expression of the transcriptional repressor RE1-silencing transcription factor (REST) and the H3K9 methyltransferase G9a that was accompanied by increased repressive H3K9me2 and REST occupancy at promoter regions of the BFCN phenotype genes Chat and Trka as well as the lineage transcription factor Lhx8. REST expression is similarly increased in the post-mortem human basal forebrain of individuals with alcohol use disorder, which is negatively correlated with ChAT expression. Administration of REST siRNA and the G9a inhibitor UNC0642 blocked and reversed the EtOH-induced loss of ChAT + IR BFCNs, directly linking REST-G9a transcriptional repression to suppression of the cholinergic neuron phenotype. These data suggest that EtOH induces a novel neuroplastic process involving neuroimmune signaling and transcriptional epigenetic gene repression resulting in the reversible suppression of the cholinergic neuron phenotype.

show abstract

Section: Resultsmentioning

confidence: 99%

HMGB1 Neuroimmune Signaling and REST-G9a Gene Repression Contribute to Ethanol-induced Reversible Suppression of the Cholinergic Neuron Phenotype

Vetreno

Fisher²,

Qin³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…They can exert strong inhibition of inflammation through different targeting proteins ( Table 2 ). The proteins that interact with the ingredients in licorice are shown in Table 2 ( Chen C. et al, 2018 ; Oh et al, 2021 ; Zhou et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid

Gao

Yang³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Licorice, a herbal product derived from the root of Glycyrrhiza species, has been used as a sweetening agent and traditional herbal medicine for hundreds of years. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Both GL and GA have pharmacological effects against tumors, inflammation, viral infection, liver diseases, neurological diseases, and metabolic diseases. However, they also exhibit differences. KEGG analysis indicated that licorice is involved in neuroactive ligand‒receptor interactions, while 18β-GA is mostly involved in arrhythmogenic right ventricular cardiomyopathy. In this article, we comprehensively review the therapeutic potential of GL and GA by focusing on their pharmacological effects and working mechanisms. We systemically examine the structure-activity relationship of GL, GA and their isomers. Based on the various pharmacological activities of GL, GA and their isomers, we propose further development of structural derivatives of GA after chemical structure modification, with less cytotoxicity but higher targeting specificity. More research is needed on the clinical applications of licorice and its active ingredients.

show abstract

“…Another possible explanation for the discrepancy might be that the rats were sacrificed, and their serum and renal tissues were obtained 24 hours after the last dose of CT contrast agent. SCr changes in patients with PC-AKI are usually observed 24–48 hours after the contrast exposure, while significant elevations in NGAL and serum Cys C are observed after 2 and 8 hours, respectively [ 5 25 ]. The levels of Cys C, KIM-1, and NGAL in this study remained unchanged, and this could be because, given the minimal renal tissue injury, they increased early and had already returned to baseline when the serum samples were obtained.…”

Section: Discussionmentioning

confidence: 99%

Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study

Bae,

Oh,

Park

et al. 2024

Korean J Radiol

Self Cite

View full text Add to dashboard Cite

Objective To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study. Materials and Methods Fifty-six Sprague–Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.47 µL/g of gadolinium-based contrast agent were injected into the tail vein. Serum levels of blood urea nitrogen, creatinine, cystatin C (Cys C), and malondialdehyde (MDA) were measured. mRNA and protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Results Levels of serum creatinine (SCr) were significantly higher in repeated CT contrast agent injection groups than in PC (0.21 ± 0.02 mg/dL for PC; 0.40 ± 0.02, 0.34 ± 0.03, and 0.41 ± 0.10 mg/dL for 2-, 4-, and 24-hour interval groups, respectively; P < 0.001). There was no significant difference in the average Cys C and MDA levels between PC and repeated CT contrast agent injection groups (Cys C, P = 0.256–0.362; MDA, P > 0.99). Additional doses of MR contrast agent did not make significant changes compared to PC in SCr ( P > 0.99), Cys C ( P = 0.262), and MDA ( P = 0.139–0.771) levels. mRNA and protein levels of KIM-1 and NGAL were not significantly different among additional CT or MR contrast agent groups ( P > 0.05). Conclusion A sufficient time interval, probably more than 24 hours, between repeated contrast-enhanced CT examinations may be necessary to avoid deterioration in renal function. However, conducting contrast-enhanced MRI on the same day as contrast-enhanced CT may not induce clinically significant kidney injury.

show abstract

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

Cited by 22 publications

References 34 publications

HMGB1 Neuroimmune Signaling and REST-G9a Gene Repression Contribute to Ethanol-induced Reversible Suppression of the Cholinergic Neuron Phenotype

HMGB1 Neuroimmune Signaling and REST-G9a Gene Repression Contribute to Ethanol-induced Reversible Suppression of the Cholinergic Neuron Phenotype

Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid

Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study

Contact Info

Product

Resources

About