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Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices
Published on: May 9, 2018
The Protective Effect of Astragalus Polysaccharides Against Cisplatin‑Induced Pulmonary Epithelial Cell Injury: An
Yan Liu1,2, Liyan Ma3, Lei Zhang4
1Henan Medical College, Zhengzhou City, Henan Province, China. Liuyan2013666@163.com.
Abstract:
Cisplatin (CDDP) is a widely used anticancer drug that generates significant oxidative stress, resulting in lung inflammation and injury. Currently, there is limited research on the related mechanisms and strategies. Astragalus polysaccharides (APS) are the main bioactive molecules in Astragalus that possess immunomodulatory, anti-inflammatory and antioxidant activities, and are clinically used for preventing pulmonary fibrosis and treating lung inflammation. Therefore, the present study aimed to investigate the protective effects of APS on CDDP-induced lung epithelial cell injury using network toxicology and network pharmacology to predict the key pathways involved in CDDP-induced injury and APS-mediated protection, and validating the predictions using in vitro assays. Our results demonstrated that APS could significantly reduce the death rate of Beas-2B cells and attenuated the oxidative stress caused by CDDP. The mitochondrial function was enhanced, mitochondrial reactive oxygen species (ROS) was suppressed, malondialdehyde (MDA) content and ferrous iron were decreased, thereby inhibiting ferroptosis and alleviating lung cell injury induced by CDDP. Therefore, the present study demonstrated that APS may attenuate CDDP-induced oxidative stress and iron overload, thereby inhibiting ferroptosis and alleviating lung cell injury. The findings of the present study may provide a potential clinical application.
Insights
Astragalus polysaccharides (APS) protect lung cells from cisplatin (CDDP) damage by reducing oxidative stress and ferroptosis. This study reveals APS as a potential therapeutic strategy for mitigating chemotherapy-induced lung injury.
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Cisplatin (CDDP) chemotherapy induces significant oxidative stress, leading to lung inflammation and injury.
- Limited research exists on the mechanisms and protective strategies against CDDP-induced lung damage.
- Astragalus polysaccharides (APS) exhibit known immunomodulatory, anti-inflammatory, and antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of APS against CDDP-induced lung epithelial cell injury.
- To predict and validate key pathways involved in CDDP-induced injury and APS-mediated protection.
- To explore the potential of APS as a therapeutic agent for lung injury.
Main Methods:
- Utilized network toxicology and network pharmacology to predict therapeutic pathways.
- Employed in vitro assays to validate predicted mechanisms.
- Assessed cell viability, oxidative stress markers (ROS, MDA), mitochondrial function, and ferroptosis indicators.
Main Results:
- APS significantly reduced Beas-2B cell death induced by CDDP.
- APS attenuated CDDP-induced oxidative stress, including decreased mitochondrial ROS and MDA levels.
- APS inhibited ferroptosis by decreasing ferrous iron and enhancing mitochondrial function, thereby alleviating lung cell injury.
Conclusions:
- APS demonstrates protective effects against CDDP-induced lung epithelial cell injury.
- APS mitigates lung injury by attenuating oxidative stress and inhibiting ferroptosis.
- APS presents a potential therapeutic strategy for clinical applications in managing chemotherapy-induced lung damage.