Edaravone Reduces Brain Injury in Hepatic Encephalopathy by Upregulation of Nrf2/HO-1 and Inhibition of NF-κB, INOS/NO and Inflammatory Cytokines

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2025 Feb 12

PMID 39937373

Authors

Keyvan Amirshahrokhi

Mahsa Imani

Affiliations

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Abstract

Background: Brain damage is the most important complication in patients with hepatic encephalopathy (HE). Oxidative stress and inflammation are essential factors in the progression of brain injury caused by HE. The aim of this study was to investigate the potential therapeutic effect of edaravone and its underlying mechanisms against brain injury associated with HE in mice.

Methods And Results: HE was induced by the injection of thioacetamide (200 mg/kg) for 2 days and then mice treated with edaravone (10 or 20 mg/kg/day, ip) for four consecutive days. The brain tissues were dissected for histopathological, biochemical, ELISA, RT-qPCR and immunofluorescence analysis. The results showed that edaravone improved the locomotor function and ameliorated brain histopathological changes in mice with HE. Edaravone inhibited oxidative stress markers by increasing the levels of glutathione, catalase, superoxide dismutase, glutathione reductase and the upregulation of nuclear erythroid 2-related factor (Nrf2)/HO-1 pathway in the brain tissue. Administration of edaravone significantly decreased the expression of p-NF-κB and iNOS. Edaravone treatment reduced the levels of NO, MPO and MMP-9 in the brain of mice. Additionally, the brain levels and expressions of inflammatory cytokines IL-1β, IL-6, TNF-α and IFN-γ were downregulated in mice treated with edaravone.

Conclusions: These results suggest that edaravone exerts significant neuroprotection by modulating of inflammatory and oxidative responses in HE and may serve as a promising agent for the treatment of brain injury associated with HE.

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