تجاوز إلى المحتوى الرئيسي

Alleviation of Copper-Induced Hepatotoxicity by Bergenin: Diminution of Oxidative Stress, Inflammation, and Apoptosis via Targeting SIRT1/FOXO3a/NF-κB Axes and p38 MAPK Signaling

Author name : Arafa Kassem A Musa
Publication Date : 2024-09-30
Journal Name : Biological Trace Element Research

Abstract

Despite its biological importance, excess copper induces organ damage, especially to the liver. Disruption of critical signaling cascades that control redox status, inflammatory responses, and cellular apoptosis significantly contributes to the copper-induced hepatotoxicity. The present work explored the hepatoprotective ability of bergenin against the copper-induced hepatotoxicity using male Wistar rats as a mammalian model. The results revealed that bergenin suppressed the copper-evoked histopathological changes and hepatocellular necrosis as indicated by decreased activity of the liver enzymes ALT and AST in the sera of the copper-intoxicated rats. It decreased hepatic copper content and the copper-induced oxidative stress as revealed by reduced lipid peroxidation and improved activity of the antioxidant enzymes thioredoxin reductase, glutathione peroxidase, catalase, and superoxide dismutase. Bergenin downregulated the inflammatory cytokines TNF-α and IL-6, and the inflammatory cell infiltration to the liver tissues. Additionally, it inhibited the copper-induced apoptosis as indicated by significant reduction in caspase-3 activity. At the molecular level, bergenin activated the antioxidant transcription factor FOXO3a, inhibited the nuclear translocation of the inflammatory transcription factor NF-κB, and suppressed the inflammatory signaling molecules p38 MAPK and c-Fos. Interestingly, bergenin improved the expression of the anti-apoptotic protein Bcl2 and reduced the pro-apoptotic protein BAX. Bergenin markedly enhanced the expression of the histone deacetylase protein SIRT1 that regulates activity of NF-κB and FOXO3a. Collectively, these findings highlight the alleviating activity of bergenin against the copper-induced hepatotoxicity via controlling oxidative stress, inflammation, and apoptosis potentially through upregulation of SIRT1, activation of FOXO3a along with suppression of NF-κB and p38 MAPK signaling.

Keywords

Copper, Hepatotoxicity, Bergenin, Wilson’s Disease, SIRT1, FOXO3a

Publication Link

https://doi.org/10.1007/s12011-024-04401-3

Block_researches_list_suggestions

Suggestions to read

Generalized first approximation Matsumoto metric
AMR SOLIMAN MAHMOUD HASSAN
HIDS-IoMT: A Deep Learning-Based Intelligent Intrusion Detection System for the Internet of Medical Things
Ahlem . Harchy Ep Berguiga
Structure–Performance Relationship of Novel Azo-Salicylaldehyde Disperse Dyes: Dyeing Optimization and Theoretical Insights
EBTSAM KHALEFAH H ALENEZY
“Synthesis and Characterization of SnO₂/α-Fe₂O₃, In₂O₃/α-Fe₂O₃, and ZnO/α-Fe₂O₃ Thin Films: Photocatalytic and Antibacterial Applications”
Asma Arfaoui
تواصل معنا