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Quercetin alleviates cadmium-induced BRL-3A cell apoptosis by inhibiting oxidative stress and the PERK/IRE1α/ATF6 signaling pathway

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Abstract

Cadmium (Cd) is a highly toxic environmental pollutant. The liver is an important metabolic organ in the body and is susceptible to Cd toxicity attacks. Quercetin (Que) is a flavonoid compound with pharmacological activities of scavenging free radicals and antioxidant activity. Previous studies have shown that Que can alleviate Cd caused hepatocyte apoptosis in rats, but the specific mechanism remains unclear. To explore the specific mechanism, we established a model of Cd toxicity and Que rescue in BRL-3A cells and used 4-phenylbutyrate (4-PBA), an endoplasmic reticulum stress (ERS) inhibitor, as positive control. Set up a control group, Cd treatment group, Cd and Que co treatment group, Que treatment group, Cd and 4-PBA co treatment group, and 4-PBA treatment group. Cell Counting Kit-8 (CCK-8) method was employed to measure cell viability. Fluorescence staining was applied to observe cell apoptosis. Flow cytometry was performed to detect reactive oxygen species levels. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot method was adopted to detect the mRNA and protein expression levels of ERS and apoptosis-related genes. The results showed that compared with the control group, the Cd treated group showed a significant decrease in cell viability (P < 0.01), an increase in intracellular ROS levels, and apoptosis. The mRNA and protein expression levels of ERS and apoptosis related factors such as GRP78, IRE1α, XBP1, ATF6, Caspase-12, Caspase-3 and Bax in the cells were significantly increased (P < 0.01), while the mRNA and protein expression levels of Bcl-2 were significantly reduced (P < 0.01). Compared with the Cd treatment group, the Cd and Que co treatment group and the Cd and 4-PBA co treatment group showed a significant increase in cell viability (P < 0.01), a decrease in intracellular ROS levels, a decrease in cell apoptosis, and a significant decrease in the expression levels of ERS and apoptosis related factors mRNA and protein (P < 0.01), as well as a significant increase in Bcl-2 mRNA and protein expression (P < 0.01). We confirmed that Que could alleviate the apoptosis caused by Cd in BRL-3A cells, and the effects of Que were similar to those of ERS inhibitor.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by grants from National Natural Science Foundation of China (No.31972753), Henan science and technology research project (222102110340).

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Authors and Affiliations

  1. College of Animal Science and Technology, Henan University of Science and Technology, No.263, Kaiyuan Avenue, 471023, Luoyang, People’s Republic of China

    Lulu Ding, Ke Wang, Ruxue Huang, Wenjing Yu, Bingzhao Yan, Bianhua Zhou, Hongwei Wang, Zijun Yang & Jicang Wang

  2. Law Hospital, Henan University of Science and Technology, No.263, Kaiyuan Avenue, 471023, Luoyang, People’s Republic of China

    Huali Zhu

  3. College of Veterinary Medicine, Yangzhou University, No.12, East Wenhui Road, 225009, Yangzhou, People’s Republic of China

    Lulu Ding & Zongping Liu

Authors
  1. Lulu Ding
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Contributions

Lulu Ding: Conceptualization, Methodology, Editing, Data analyses, Writing. Huali Zhu: Methodology, Editing, Supervision. Ke Wang: Methodology, Supervision. Ruxue Huang: Data curation, Data analyses, Editing. Wenjing Yu: Data curation, Data analyses. Bingzhao Yan: Conceptualization, Methodology. Bianhua Zhou: Supervision, Resources. Hongwei Wang: Supervision, Resources. Zijun Yang: Supervision, Resources. Zongping Liu: Supervision, Resources. Jicang Wang: Conceptualization, Methodology, Editing, Supervision. All authors reviewed the manuscript.

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Correspondence to Jicang Wang.

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Ding, L., Zhu, H., Wang, K. et al. Quercetin alleviates cadmium-induced BRL-3A cell apoptosis by inhibiting oxidative stress and the PERK/IRE1α/ATF6 signaling pathway. Environ Sci Pollut Res 30, 125790–125805 (2023). https://doi.org/10.1007/s11356-023-31189-x

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