{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:05:52Z","timestamp":1789707952172,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Subject of Biology operated by Jilin Agricultural Science and Technology College","award":["20230071"],"award-info":[{"award-number":["20230071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The neonicotinoid insecticide imidacloprid (IMD), widely used in agriculture, poses potential risks to aquatic ecosystems, yet its hepatotoxic mechanisms in freshwater fish remain poorly understood. This study investigates the roles of ferroptosis, mitochondrial dysfunction, inflammation, and the miR-153c\/SQSTM1-mediated ferritinophagy pathway in IMD-induced hepatotoxicity in carp (Cyprinus carpio) hepatocytes. Using the CCK-8 assay, 0.6 \u03bcM IMD was selected for subsequent experiments. IMD exposure triggered ferroptosis, evidenced by increased intracellular Fe2+ accumulation, upregulated pro-ferroptotic gene and protein expression, and downregulated ferroptosis inhibitors (SLC7A11 and GPX4). Mitochondrial dysfunction was confirmed by reduced ATP content, decreased mtDNA levels, and a lowered NADPH\/NADP+ ratio, along with aberrant expression of mitochondrial fission (Fis1 and Drp1) and fusion (Mfn1 and TFAM) genes. Additionally, IMD induced oxidative stress (elevated ROS and MDA; decreased T-AOC, CAT, and SOD activities) and a pronounced inflammatory response with upregulated pro-inflammatory cytokines. Mechanistically, IMD downregulated miR-153c, with concomitant upregulation of SQSTM1 at both the mRNA and protein levels, and dual-luciferase assays validated SQSTM1 as a direct target of miR-153c. miR-153c overexpression attenuated IMD-induced ferritinophagy, ferroptosis, and inflammation via the miR-153c\/SQSTM1 axis. Collectively, these findings demonstrate that IMD induces hepatotoxicity in carp by triggering ferroptosis, mitochondrial dysfunction, and inflammation through the miR-153c\/SQSTM1-mediated ferritinophagy pathway, providing mechanistic insights and potential targets for mitigating IMD\u2019s ecological risks.<\/jats:p>","DOI":"10.3390\/toxics14090814","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imidacloprid-Induced Ferroptosis-Associated Injury in Common Carp Hepatocytes: Potential Involvement of the miR-153c\/SQSTM1 Axis"],"prefix":"10.3390","volume":"14","author":[{"given":"Huijie","family":"Chen","sequence":"first","affiliation":[{"name":"School of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology College, 77 Hanlin Road, Jilin 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology College, 77 Hanlin Road, Jilin 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenkai","family":"Yao","sequence":"additional","affiliation":[{"name":"Vaccine Inspection Department, Jilin Provincial Drug Inspection and Verification Center, No. 657 Zhanjiang Road, Economic and Technological Development Zone, Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Drug and Cosmetics Inspection Laboratory, Inspection and Testing Center, Jiyuan Industry-City Integration Demonstration Zone, No. 181 North Wenchang Road, Jiyuan 459000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology College, 77 Hanlin Road, Jilin 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9767-256X","authenticated-orcid":false,"given":"Lei","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology College, 77 Hanlin Road, Jilin 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61345","DOI":"10.1007\/s11356-024-35178-6","article-title":"An overview on the fate and behavior of imidacloprid in agricultural environments","volume":"31","author":"Fouad","year":"2024","journal-title":"Environ. 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