Metabolomic changes associated with behavioral and molecular findings: Triclocarban toxicity in the zebrafish model.
📄 Abstract
Triclocarban (TCC), an antimicrobial agent used in personal care products, has been widely detected in aquatic ecosystems and has raised significant concerns for aquatic organisms and human health. This study aimed to investigate the neurotoxic effects of TCC exposure, a broad-spectrum bactericide, through behavioral, molecular, pathological, and metabolomic analyses. For this purpose, adult zebrafish were exposed to TCC at doses of 3, 10, and 30 μg/L for 96 h, and their brain tissues were removed. Subsequently, behavioral (anxiety and circadian rhythm tests), molecular (qPCR), histopathological, and metabolomic analyses were performed on these fish. The data obtained showed that TCC treatment increased anxiety-like behaviors in zebrafish and caused disruptions in the circadian rhythm. Additionally, it was determined that the expression levels of both core clock genes (Bmal and Gnat2) and genes associated with neuroplasticity, stress response, and neurotransmission (Bdnf, Crhr, 5-ht4, Ache) changed significantly in a dose-dependent manner compared to the control group. Additionally, it was observed that TCC increased degeneration and necrosis in the brain in parallel with the dose increase, while raising 8-OHdG and BDNF protein levels and decreasing NRF2 and SIRT1 protein levels. When metabolomic analysis data were evaluated, it was determined that TCC, especially at the highest dose, significantly altered metabolite levels. These results reveal that TCC, beyond being an environmental pollutant, may cause behavioral disorders and neurotoxic effects.