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

Abstract

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 LC 50 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 LC 50 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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