Astragaloside IV protects LO2 cells from oxidative damage caused by radiation-induced bystander effect through Akt/Nrf2 pathway

Author:

Wan Danting1ORCID,Zhu Zihao1ORCID,Zhou Jie1ORCID,Deng Zhengzheng1ORCID,Lei Pengyuan1ORCID,Liu Qi1ORCID,Sun Xiaoya1ORCID,Huang Bo1ORCID

Affiliation:

1. Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China , 28 West Changsheng Road, Hengyang, 421001 , China

Abstract

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.

Funder

Natural Science Foundation of Hunan Province

Health Commission Scientific Research Project of Hunan Province

Scientific Research Project of Education Bureau of Hunan Province

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Toxicology

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