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The study aimed to investigate the toxic impacts of TCS on <jats:italic>Labeo rohita<\/jats:italic>, revealing a 96-h LC<jats:sub>50<\/jats:sub> of 0.742\u00a0mg\/L. Well-acclimatized fish were categorised into three groups: one control and two treatment (T1 and T2) that were exposed to 1\/10th and 1\/5th of 96-h LC<jats:sub>50<\/jats:sub> i.e., 0.0742\u00a0mg\/L and 0.148\u00a0mg\/L, respectively for 6 weeks under semi-static condition. Significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) elevated extents of reactive oxygen species (ROS) in the liver indicated enhanced oxidative stress. The activities of enzymatic antioxidants viz. superoxide dismutase (SOD) and catalase (CAT) were significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) increased while the reduced glutathione (GSH) levels were significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) decreased in a dose- and duration-dependent manner. A significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) increase was observed in the lipid peroxidation (LPO) rate, which coincided with disruptions in the histological structure of the liver. Significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) induction in Micronuclei frequency validated genomic instability. Furthermore, Endoplasmic Reticulum (ER) stress was marked by the increased intracellular calcium levels and elevated expression of <jats:italic>grp78<\/jats:italic>,<jats:italic> chop<\/jats:italic>,<jats:italic> atf4<\/jats:italic>,<jats:italic> perk<\/jats:italic>,<jats:italic> eIF2\u03b1<\/jats:italic> and <jats:italic>gadd34<\/jats:italic> in TCS-exposed groups. Moreover, the consequent activation of <jats:italic>bax<\/jats:italic>,<jats:italic> caspase-3<\/jats:italic>,<jats:italic> caspase-9<\/jats:italic>,<jats:italic> apaf-1<\/jats:italic> and the regulation of <jats:italic>bcl-2<\/jats:italic> due to ER-stress, ultimately resulted in apoptosis of hepatocytes. Pearson correlation matrix and Principal Component Analysis (PCA) further underscored key interactions among parameters. Our findings demonstrate that the TCS, at its sub-lethal concentrations, is causing severe anomalies and even cell-death via triggering ER-stress-mediated apoptotic pathway in the fish liver.<\/jats:p>","DOI":"10.1038\/s41598-025-93997-0","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T15:50:15Z","timestamp":1747410615000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-1256","authenticated-orcid":false,"given":"Abha","family":"Trivedi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Banaee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumman","family":"Bakhasha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeti","family":"Arya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamlesh K.","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Faggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"93997_CR1","doi-asserted-by":"publisher","first-page":"125086","DOI":"10.1016\/j.chemosphere.2019.125086","volume":"241","author":"C Wang","year":"2020","unstructured":"Wang, C. et al. 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