Astragaloside IV Protects LO2 Cells from Oxidative Damage Caused by Radiation-induced Bystander Effect Through Akt/Nrf2 Pathway

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2023 Sep 4

PMID 37663802

Authors

Danting Wan

Zihao Zhu

Jie Zhou

Zhengzheng Deng

Pengyuan Lei

Qi Liu

Xiaoya Sun

Bo Huang

Affiliations

Soon will be listed here.

Abstract

Background: The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear.

Objective: This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells.

Methods: To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure.

Results: The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE.

Conclusion: This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.

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