{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:19:16Z","timestamp":1790288356914,"version":"4.1.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008867","name":"Zhejiang Provincial Education Department","doi-asserted-by":"crossref","award":["Y202353817"],"award-info":[{"award-number":["Y202353817"]}],"id":[{"id":"10.13039\/501100008867","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Acute kidney injury (AKI) is a critical clinical syndrome with limited therapeutic options. This study investigated the renoprotective effects of lycopene, a potent antioxidant, in both in vivo and in vitro AKI models. In a murine cecal ligation and puncture (CLP)-induced sepsis-AKI model, pretreatment with lycopene (10, 20, 40 mg\/kg) dose-dependently ameliorated renal histopathological damage (HE staining) and restored serum biomarkers (AST, ALT, BUN, CREA). Mechanistically, lycopene suppressed oxidative stress and apoptosis by downregulating the PI3K\/Akt axis: it significantly reversed the CLP-induced upregulating of p-PI3K and p-Akt, and the pro-apoptotic proteins (Bax, Cleaved Caspase-3), while increasing Nrf 2 and SOD1. Consistent results were observed in LPS- and H\u2082O\u2082-induced cellular AKI models, where lycopene attenuated cell death and restored redox homeostasis in a dose-dependent manner. Immunofluorescence assays further validated these trends. Crucially, PI3K siRNA or cDNA transfection experiments confirmed that lycopene\u2019s antioxidant and anti-apoptotic effects were PI3K-dependent. Our findings highlight lycopene as a promising therapeutic agent for AKI, acting via PI3K\/Akt-mediated activation of Nrf 2 to counteract oxidative damage and apoptosis. This study provides novel insights into the molecular mechanisms underlying lycopene\u2019s renoprotection and supports its potential clinical translation for sepsis or oxidative stress-associated AKI.<\/jats:p>","DOI":"10.1371\/journal.pone.0339565","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T18:26:43Z","timestamp":1766514403000},"page":"e0339565","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lycopene inhibits ER stress and apoptosis while modulating PI3K\/AKT and enhancing antioxidant and anti-apoptotic 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