Mechanistic insights into novel triclosan target pathways in Neocaridina denticulata revealed by multi-omics integration.

Crustaceans have received comparatively limited attention in the identification of novel target pathways of triclosan (TCS) toxicity relative to vertebrates and common model species. In this study, we employed an integrated multi-omics approach, including transcriptomics, proteomics, and metabolomics, to elucidate the molecular mechanisms underlying TCS toxicity in the freshwater shrimp Neocaridina denticulata. Individuals were exposed to three TCS concentrations (1, 5, and 10 μg L-1), including an environmentally relevant level, for 24 h. TCS body accumulation, along with molecular and biochemical alterations in whole-body tissues, was assessed through omics integration and in silico analyses. Results showed that TCS induced reactive oxygen species generation through disruption of the mitochondrial electron transport chain, accompanied by an atypical antioxidant response characterized by downregulation of the first-line antioxidant enzymes. Although endoplasmic reticulum stress markers were not significantly activated, the expression of mitochondrial chaperone-related molecules increased, likely reflecting mitochondrial oxidative stress. A compensatory metabolic response was also evident, in which amino acid metabolism appeared to supplement reduced glucose utilization. Impaired Complex I activity decreased NAD⁺ levels, driving increased LDHC expression as a compensatory mechanism to maintain TCA cycle flux. Additionally, alterations in Ca2+-dependent, muscle contraction-related genes were detected in the sarcomere. Collectively, these findings reveal distinct TCS-induced toxicological pathways in N. denticulata, underscoring mechanistic differences between crustaceans and vertebrate models. SYNOPSYS: Integrated multi-omics analyses reveal triclosan-induced mitochondrial dysfunction, atypical antioxidant responses, and distinct mechanistic toxicity pathways in the crustacean Neocaridina denticulata.