Naringin Regulates Mitochondrial Dynamics to Protect Against Acetaminophen-induced Hepatotoxicity by Activating the AMPK/Nrf2 Signaling Pathway in Vitro

Overview

Journal Braz J Med Biol Res

Specialties Biology
General Medicine

Date 2022 Oct 19

PMID 36259797

Authors

Qiao Wu

Pengfei Yu

Yanzhen Bi

Zhijie Li

Wei Guo

Yu Chen

Zhongping Duan

Affiliations

Soon will be listed here.

Abstract

Naringin (Nar) has been reported to exert potential hepatoprotective effects against acetaminophen (APAP)-induced injury. Mitochondrial dysfunction plays an important role in APAP-induced liver injury. However, the protective mechanism of Nar against mitochondrial damage has not been elucidated. Therefore, the aim of this study was to investigate the hepatoprotective effects of Nar against APAP and the possible mechanisms of actions. Primary rat hepatocytes and HepG2 cells were utilized to establish an in vitro model of APAP-induced hepatotoxicity. The effect of APAP and Nar on cell viability was evaluated by a CCK8 assay and detection of the concentrations of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. The cellular concentrations of biomarkers of oxidative stress were measured by ELISA. The mRNA expression levels of APAP-related phase II enzymes were determined by real-time PCR. The protein levels of Nrf2, phospho (p)-AMPK/AMPK, and biomarkers of mitochondrial dynamics were determined by western blot analysis. The mitochondrial membrane potential (MMP) was measured by high-content analysis and confocal microscopy. JC-1 staining was performed to evaluate mitochondrial depolarization. Nar pretreatment notably prevented the marked APAP-induced hepatocyte injury, increases in oxidative stress marker expression, reductions in the expression of phase II enzymes, significant loss of MMP, mitochondrial depolarization, and mitochondrial fission in vitro. In conclusion, Nar alleviated APAP-induced hepatocyte and mitochondrial injury by activating the AMPK/Nrf2 pathway to reduce oxidative stress in vitro. Applying Nar for the treatment of APAP-induced liver injury might be promising.

Citing Articles

Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders.

Peng Y, Qu R, Xu S, Bi H, Guo D Heliyon. 2024; 10(3):e24619.

PMID: 38317884 PMC: 10839891. DOI: 10.1016/j.heliyon.2024.e24619.

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