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We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 \u03bcM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 \u03bcM) was significantly reduced, while the death rate in the medium dose group (25 \u03bcM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.<\/jats:p>","DOI":"10.3390\/molecules28134897","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T02:09:17Z","timestamp":1687399757000},"page":"4897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective Effect of Astragaloside IV against Cadmium-Induced Damage on Mouse Renal Podocytes (MPC5)"],"prefix":"10.3390","volume":"28","author":[{"given":"Pin","family":"Gong","sequence":"first","affiliation":[{"name":"School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"},{"name":"School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9628-0946","authenticated-orcid":false,"given":"Shan","family":"Yue","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"},{"name":"School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxiong","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"},{"name":"School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-6258","authenticated-orcid":false,"given":"Wenjuan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"},{"name":"School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-4450","authenticated-orcid":false,"given":"Wenbo","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"},{"name":"School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Xi\u2019an University of Science and Technology, Xi\u2019an 710054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-0969","authenticated-orcid":false,"given":"Yuxi","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"},{"name":"School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19619","DOI":"10.1073\/pnas.1908706116","article-title":"The single-cell transcriptomic landscape of early human diabetic nephropathy","volume":"116","author":"Wilson","year":"2019","journal-title":"Proc. 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