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

Introduction

Triclosan (TCS) is a synthetic and lipophilic compound with the IUPAC name is 2,4,4′-trichloro-2′-hydroxydiphenyl ether or 5-chloro-2-(2,4-dichlorophenoxy) phenol. It is widely used globally as an ingredient in disinfectants, soaps, detergents, toothpaste, mouthwash, fabrics, deodorant, shampoo and plastic additives, in addition to numberless other personal care, veterinary, pharmaceutical, industrial and household products, due to its antimicrobial properties¹. Moreover, the use of TCS as a household sanitizing agent, in kitchenware, textiles and plastic toys has also been reported².

Due to misuse, overuse, slow absorption, high water solubility and resistance to degradation, anti-microbial agents are often pervasive in the environment³. The widespread use of TCS in various products creates multiple pathways for the compound to enter the environment, particularly through wastewater. Studies have shown that since the COVID-19 pandemic, the heightened use and constant release of TCS from soaps and sanitizers have increased considerably⁴. While TCS plays an important role in infection prevention and has been effective in controlling microbial growth in medical and consumer products, its accumulation in the environment has raised concerns due to potential risks, including antimicrobial resistance, endocrine disruption, bioaccumulation in aquatic ecosystems, and toxicity to non-target organisms, including humans⁵. Furthermore, developing alternatives that maintain antimicrobial effectiveness while minimizing ecological impact remains a significant challenge. These issues highlight the need for a careful evaluation of TCS’s benefits and potential hazards to both human health and the environment⁶.

Approximately 96% of TCS from consumer products is discharged into residential drains, which subsequently enter the wastewater treatment plants (WWTP)^7,8. Inappropriate wastewater treatment and continuous sewage emanations into river surface water ultimately contaminate aquatic ecosystems⁴. Due to COVID-19 measures, the worldwide river contamination with TCS was reported to be enhanced by 33%⁹. Its presence has been detected in various biological fluids, including urine, breast milk and blood plasma, as well as tissues like the liver, placenta, adipose and brain in various quantities^10,11.

As an antibacterial agent, TCS targets multiple sites within cells and the cytoplasm, potentially interfering with gene transcription and disrupting signaling pathways¹². The Endoplasmic Reticulum (ER), a crucial intracellular organelle, plays a vital role in protein synthesis, folding, modification, lipid metabolism, and...