Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita

Abstract Triclosan (TCS), a widely used antimicrobial, has emerged as a concerning aquatic pollutant, especially post-COVID-19 due to increased disinfectant use. The study aimed to investigate the toxic impacts of TCS on Labeo rohita, revealing a 96-h LC50 of 0.742 mg/L. Well-acclimatized fish were...

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Main Authors: Abha Trivedi, Vaishnavi Saxena, Mahdi Banaee, Jumman Bakhasha, Neeti Arya, Kamlesh K. Yadav, Maria Giovanna Rizzo, Caterina Faggio
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-93997-0
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author Abha Trivedi
Vaishnavi Saxena
Mahdi Banaee
Jumman Bakhasha
Neeti Arya
Kamlesh K. Yadav
Maria Giovanna Rizzo
Caterina Faggio
author_facet Abha Trivedi
Vaishnavi Saxena
Mahdi Banaee
Jumman Bakhasha
Neeti Arya
Kamlesh K. Yadav
Maria Giovanna Rizzo
Caterina Faggio
author_sort Abha Trivedi
collection DOAJ
description Abstract Triclosan (TCS), a widely used antimicrobial, has emerged as a concerning aquatic pollutant, especially post-COVID-19 due to increased disinfectant use. The study aimed to investigate the toxic impacts of TCS on Labeo rohita, revealing a 96-h LC50 of 0.742 mg/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 LC50 i.e., 0.0742 mg/L and 0.148 mg/L, respectively for 6 weeks under semi-static condition. Significantly (p < 0.05) 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 (p < 0.05) increased while the reduced glutathione (GSH) levels were significantly (p < 0.05) decreased in a dose- and duration-dependent manner. A significant (p < 0.05) increase was observed in the lipid peroxidation (LPO) rate, which coincided with disruptions in the histological structure of the liver. Significant (p < 0.05) induction in Micronuclei frequency validated genomic instability. Furthermore, Endoplasmic Reticulum (ER) stress was marked by the increased intracellular calcium levels and elevated expression of grp78, chop, atf4, perk, eIF2α and gadd34 in TCS-exposed groups. Moreover, the consequent activation of bax, caspase-3, caspase-9, apaf-1 and the regulation of bcl-2 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.
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spelling doaj-art-22d61a533c8042b9a0a5fd20d207abec2025-08-20T03:10:20ZengNature PortfolioScientific Reports2045-23222025-05-0115111810.1038/s41598-025-93997-0Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohitaAbha Trivedi0Vaishnavi Saxena1Mahdi Banaee2Jumman Bakhasha3Neeti Arya4Kamlesh K. Yadav5Maria Giovanna Rizzo6Caterina Faggio7Toxicogenomics Laboratory, Department of Animal Science, M.J.P. Rohilkhand UniversityToxicogenomics Laboratory, Department of Animal Science, M.J.P. Rohilkhand UniversityDepartment of Environmental Sciences, Faculty of Natural Resources, Behbahan Khatam Alanbia University of TechnologyToxicogenomics Laboratory, Department of Animal Science, M.J.P. Rohilkhand UniversityToxicogenomics Laboratory, Department of Animal Science, M.J.P. Rohilkhand UniversityDepartment of Zoology, Government Degree CollegeDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of MessinaDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of MessinaAbstract Triclosan (TCS), a widely used antimicrobial, has emerged as a concerning aquatic pollutant, especially post-COVID-19 due to increased disinfectant use. The study aimed to investigate the toxic impacts of TCS on Labeo rohita, revealing a 96-h LC50 of 0.742 mg/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 LC50 i.e., 0.0742 mg/L and 0.148 mg/L, respectively for 6 weeks under semi-static condition. Significantly (p < 0.05) 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 (p < 0.05) increased while the reduced glutathione (GSH) levels were significantly (p < 0.05) decreased in a dose- and duration-dependent manner. A significant (p < 0.05) increase was observed in the lipid peroxidation (LPO) rate, which coincided with disruptions in the histological structure of the liver. Significant (p < 0.05) induction in Micronuclei frequency validated genomic instability. Furthermore, Endoplasmic Reticulum (ER) stress was marked by the increased intracellular calcium levels and elevated expression of grp78, chop, atf4, perk, eIF2α and gadd34 in TCS-exposed groups. Moreover, the consequent activation of bax, caspase-3, caspase-9, apaf-1 and the regulation of bcl-2 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.https://doi.org/10.1038/s41598-025-93997-0TriclosanFishEndoplasmic reticulum stressPERK pathwayUnfolded protein response
spellingShingle Abha Trivedi
Vaishnavi Saxena
Mahdi Banaee
Jumman Bakhasha
Neeti Arya
Kamlesh K. Yadav
Maria Giovanna Rizzo
Caterina Faggio
Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita
Scientific Reports
Triclosan
Fish
Endoplasmic reticulum stress
PERK pathway
Unfolded protein response
title Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita
title_full Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita
title_fullStr Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita
title_full_unstemmed Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita
title_short Unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in Labeo rohita
title_sort unveiling the crosstalk between unfolded protein response and apoptosis in triclosan induced hepatotoxicity in labeo rohita
topic Triclosan
Fish
Endoplasmic reticulum stress
PERK pathway
Unfolded protein response
url https://doi.org/10.1038/s41598-025-93997-0
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