Integrated Proteomics and Metabolomics Assessment Indicated Metabolic Alterations in Hypothalamus of Mice Exposed to Triclosan

Abstract

Triclosan (TCS) is a ubiquitous antimicrobial used in many daily consumer products. It has been reported to induce endocrine disrupting effects at low doses in mammals, disturbing sex hormone function and thyroid function. The hypothalamus plays a crucial role in the maintenance of neuroendocrine function and energy homeostasis. We speculated that the adverse effects of TCS might be related to the disturbance of metabolic processes in hypothalamus. The present study aimed at investigating the effects of TCS exposure on the protein and metabolite profiles in hypothalamus of mice. Male C57BL/6 mice were orally exposed to TCS at the dosage of 10 mg/kg/d for 13 weeks. The hypothalamus was isolated and processed for mass spectrometry (MS)-based proteomics and metabolomics analyses. The results showed that a 10.6% decrease (P = 0.066) in body weight gain was observed in the TCS exposure group compared with vehicle control group. Differential analysis defined 52 proteins and 57 metabolites that delineated TCS exposed mice from vehicle controls. Among the differential features, multiple proteins and metabolites were found to play vital roles in neuronal signaling and function. Bioinformatics analysis revealed that these differentially expressed proteins and metabolites were involved in four major biological processes, including glucose metabolism, purine metabolism, neurotransmitter release, and neural plasticity, suggesting the disturbance of homeostasis in energy metabolism, mitochondria function, neurotransmitter system, and neuronal function. Our results may provide insights into the neurotoxicity of TCS and extend our understanding of the biological effects induced by TCS exposure.

Triclosan Reprograms Immunometabolism and Activates the Inflammasome in Human Macrophages

“…1,2,35 Although the metabolic profiles disturbed by triclosan were different, it was found that triclosan significantly disrupted energy metabolism. 1,2,35 To obtain more unknown metabolic profiles, nontargeted metabolomics is used here, and future analysis of samples with authentic standards is needed to validate compound names and pathway information found in untargeted metabolomics.…”

“…Overall, triclosan exposure disrupts macrophage metabolism by disrupting central carbon metabolism and purine metabolism. Untargeted metabolomics has also been used by other researchers to study the effects of triclosan on a variety of model organisms, such as hepatocytes, mouse hypothalamus, and zebrafish embryos. ,, Although the metabolic profiles disturbed by triclosan were different, it was found that triclosan significantly disrupted energy metabolism. ,, To obtain more unknown metabolic profiles, nontargeted metabolomics is used here, and future analysis of samples with authentic standards is needed to validate compound names and pathway information found in untargeted metabolomics.…”

“…Triclosan (TCS, Figure S1) is frequently utilized in a variety of consumer products due to its broad-spectrum antibacterial effects. − Considering its potential risks, triclosan has recently been banned by several government agencies. , However, triclosan is still widely used in toothpastes, mouthwashes, and hand sanitizers worldwide. In particular, the use of triclosan has increased significantly with the widespread use of hand sanitizers following the coronavirus disease 2019 (COVID-19) outbreak .…”

Antiseptic drugs and disinfectants with experience of the second year of COVID-19 pandemic-related side effects

“…A study in human ovarian granulosa cells in vitro showed that triclosan may increase estradiol and progesterone levels with upregulated expression of steroidogenesis gene ( Du et al, 2021 ) [E]. A study in mice exposed to triclosan for 13 weeks showed a decrease in body weight and metabolic alterations in the hypothalamus ( Huang et al, 2021 ) [E]. Using in vitro and gene-profiling assays, the estrogenic activity of triclosan was confirmed ( Yoon & Kwack, 2021 ) [E].…”