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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 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.

SUBMITTER: Oh H

PROVIDER: S-EPMC8329191 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and Purpose: Clinical outcome and mortality after endovascular thrombectomy (EVT) in patients with ischemic stroke are commonly assessed after 3 months. In patients with acute kidney injury (AKI), unfavorable results for 3-month mortality have been reported. However, data on the in-hospital mortality after EVT in this population are sparse. In the present study, we assessed whether AKI impacts in-hospital and 3-month mortality in patients undergoing EVT. Materials and Methods: From a prospectively recruiting database, consecutive acute ischemic stroke patients receiving EVT between 2010 and 2018 due to acute large vessel occlusion were included. Post-contrast AKI (PC-AKI) was defined as an increase of baseline creatinine of ≥0.5 mg/dL or >25% within 48 h after the first measurement at admission. Adjusting for potential confounders, associations between PC-AKI and mortality after stroke were tested in univariate and multivariate logistic regression models. Results: One thousand one hundred sixty-nine patients were included; 166 of them (14.2%) died during the acute hospital stay. Criteria for PC-AKI were met by 29 patients (2.5%). Presence of PC-AKI was associated with a significantly higher risk of in-hospital mortality in multivariate analysis [odds ratio (OR) = 2.87, 95% confidence interval (CI) = 1.16-7.13, p = 0.023]. Furthermore, factors associated with in-hospital mortality encompassed higher age (OR = 1.03, 95% CI = 1.01-1.04, p = 0.002), stroke severity (OR = 1.05, 95% CI = 1.03-1.08, p < 0.001), symptomatic intracerebral hemorrhage (OR = 3.20, 95% CI = 1.69-6.04, p < 0.001), posterior circulation stroke (OR = 2.85, 95% CI = 1.72-4.71, p < 0.001), and failed recanalization (OR = 2.00, 95% CI = 1.35-3.00, p = 0.001). Conclusion: PC-AKI is rare after EVT but represents an important risk factor for in-hospital mortality and for mortality within 3 months after hospital discharge. Preventing PC-AKI after EVT may represent an important and potentially lifesaving effort in future daily clinical practice.

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

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