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This study investigates the effects of different concentrations of AgNPs (10, 20, 50, and 100\u00a0\u00b5g\/L) and bulk silver nitrate (AgNO<jats:sub>3<\/jats:sub>) at 100\u00a0\u00b5g\/L, on the hepatic antioxidant defense system, oxidative stress markers, and liver histopathology of Nile tilapia (Oreochromis niloticus), with sampling conducted biweekly over six weeks. AgNPs were chemically synthesized using trisodium acetate, yielding an average crystallite size of 29.92\u00a0nm. Results demonstrated that both antioxidant enzyme activities and lipid peroxidation (LPO) levels in Nile tilapia exhibited a dose-dependent response. During weeks 2 and 4, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), activities, along with LPO levels were significantly increased, while TAC levels notably decreased, especially at higher AgNPs concentrations. By week 6, antioxidant enzyme activities were suppressed, and LPO levels were markedly elevated in the higher AgNPs groups (AgNPs-50 and AgNPs-100). In contrast, fish exposed to bulk AgNO<jats:sub>3<\/jats:sub> exhibited activation of the enzymatic antioxidant system, although LPO levels remained elevated throughout the experimental period. Histopathological analysis revealed progressive liver damage, including congestion, dilation, fibrosis, fatty degeneration, and necrosis. These effects were more pronounced with higher doses of AgNPs. The results showed a mitigation response among all experimental groups during the first four weeks. However, by week 6, the antioxidant system in Nile tilapia exposed to higher doses of AgNPs failed to cope with the induced oxidative stress. This underscores the significantly higher ecological risks associated with prolonged exposure to AgNPs compared to AgNO<jats:sub>3<\/jats:sub>, revealing a critical concern for the stability and health of aquatic ecosystems.<\/jats:p>","DOI":"10.1038\/s41598-025-97731-8","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:02:51Z","timestamp":1746183771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Oxidative stress responses and histological changes in the liver of Nile tilapia exposed to silver bulk and nanoparticles"],"prefix":"10.1038","volume":"15","author":[{"given":"Hala E.","family":"Ghannam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa I.","family":"Khedr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwa","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasr M.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally M.","family":"Salaah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"97731_CR1","doi-asserted-by":"publisher","unstructured":"Salaah, S. 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