{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:02:45Z","timestamp":1787731365400,"version":"build-2784847793"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Project of Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["2023D01D04"],"award-info":[{"award-number":["2023D01D04"]}]},{"name":"Key Project of Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["32060787"],"award-info":[{"award-number":["32060787"]}]},{"name":"Key Project of Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["SKL-HIDCA-2023-12"],"award-info":[{"award-number":["SKL-HIDCA-2023-12"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2023D01D04"],"award-info":[{"award-number":["2023D01D04"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32060787"],"award-info":[{"award-number":["32060787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["SKL-HIDCA-2023-12"],"award-info":[{"award-number":["SKL-HIDCA-2023-12"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Project of the State Key Laboratory of Pathogenesis, Prevention and Treatment of High-Incidence Diseases in Central Asia","award":["2023D01D04"],"award-info":[{"award-number":["2023D01D04"]}]},{"name":"Open Project of the State Key Laboratory of Pathogenesis, Prevention and Treatment of High-Incidence Diseases in Central Asia","award":["32060787"],"award-info":[{"award-number":["32060787"]}]},{"name":"Open Project of the State Key Laboratory of Pathogenesis, Prevention and Treatment of High-Incidence Diseases in Central Asia","award":["SKL-HIDCA-2023-12"],"award-info":[{"award-number":["SKL-HIDCA-2023-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>(1) Background: Cystic echinococcosis (CE) is an Echinococcus granulosus-induced worldwide parasitic zoonosis and is a recognized public health and socio-economic concern. The liver is the major target organ for CE\u2019s infective form protoscolex (PSCs), which causes serious liver damage and endangers the host\u2019s life. Reports show that PSC infection causes liver cell Fe2+ metabolism disorder and abnormal deposition of Fe2+ in liver cells and results in liver cell death. However, whether PSC-induced liver cell death is associated with ferroptosis remains to be clarified. (2) Methods: Using both an in vivo rat model and an in vitro co-culture of PSCs and the cell system, we studied the histopathological progress of PSCs infection and the cytopathogenesis of PSC-induced cell death in the liver. Hepatic-injury-related ferroptosis signaling pathways were identified by proteomics analysis at various stages of PSCs infection, and physiological and the biochemical indexes and expression of pathway proteins related to hepatic ferroptosis were studied. Ferrostatin-1, a ferroptosis inhibitor, was employed for in vivo interference with early protoscolices infection in rats, and the effects of the inhibition of hepatocyte ferroptosis on hepatocyte injury and the generation of fibrotic cysts were investigated. Additionally, PSCs were exposed to in vitro co-culture with BRL, a rat hepatocyte line, to clarify the direct influences of PSCs on BRL ferroptosis. (3) Results: The results of our in vivo studies revealed that PSCs infection induced Fe2+ enrichment in liver cells surrounding the PSCs cysts, cellular oxidation, and liver tissue damage along with the prolongation of PSCs parasitism. The results of our in vitro studies verified the ability of PSCs to directly induce ferroptosis, the formation of fibrotic cysts, and alteration of the iron metabolism of liver cells. The analysis of KEGG signaling pathways revealed that ferroptosis- and ROS-related pathways were significantly induced with PSCs infection. Using Ferrostatin-1 effectively blocked ferroptosis, reversed Fe2+ content, reduced liver cell oxidation, and reduced PSC-induced fibrosis cysts. (4) Conclusions: Our study reveals the histopathological progress of PSC infection and the cytopathogenesis of PSC-induced ferroptosis. Ferrostatin-1 effectively blocked PSCs infection and PSC-induced cell death in vivo and in vitro. Accordingly, the inhibition of PSC-induced hepatocyte ferroptosis may be an effective method in the control of Echinococcus granulosus infection and should be seriously considered in clinical studies.<\/jats:p>","DOI":"10.3390\/cells14050328","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T07:46:57Z","timestamp":1740383217000},"page":"328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Echinococcus granulosus-Induced Liver Damage Through Ferroptosis in Rat Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Shaohua","family":"Zhai","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"},{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqi","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Lai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunlei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6459-7932","authenticated-orcid":false,"given":"Jiyu","family":"Guan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.actatropica.2017.07.013","article-title":"The echinococcoses in Asia: The present situation","volume":"176","author":"Ito","year":"2017","journal-title":"Acta Trop."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, X., Gong, W., Duan, C., Cai, H., Shen, Y., and Cao, J. 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