Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD

Abstract

People are frequently and unintentionally exposed to many chemical compounds, such as environmental pollutants and endocrine-disrupting chemicals (EDCs), in food and from the atmosphere. In particular, endocrine-disrupting TBBPA and dioxins are found in human breast milk and in the body. Conventional studies evaluate toxicity by administering a single substance to cells or animals, but evaluation of the toxicity of mixtures of these ingested compounds is essential for “true” toxicological assessment. We evaluated toxic effects in vitro using human mesenchymal stem cells (hMSCs). TBBPA increased the number of lipid droplets, and upregulated the expression of adipocyte-related mRNA, aP2 and LPL, through a PPARγ-dependent mechanism. TCDD suppressed lipid droplets and adipocyte-related mRNA levels. Adipocyte differentiation was stimulated by TBBPA and inhibited by TCDD in a dose-dependent manner. TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances.

A dose-dependent effect of dimethyl sulfoxide on lipid content, cell viability and oxidative stress in 3T3-L1 adipocytes

“…In such cases the interaction on mitochondrial energetics, oxidative stress and other antioxidant enzymes should be considered. These findings also add to the current debate on the danger associated with exposure of individuals to complex mixtures of chemicals via food, water and commercial products consumption, as previously discussed [ [23] , [24] , [25] , [26] ]. Although DMSO offers various benefits, especially for its use as a solvent, caution should be taken when working with higher concentrations as they can induce cellular stress and cell death.…”

“…Although DMSO offers various benefits, especially for its use as a solvent, caution should be taken when working with higher concentrations as they can induce cellular stress and cell death. Furthermore, higher concentrations of DMSO could potentially influence the results of other toxicological studies when used in mixture with other chemicals [ [23] , [24] , [25] , [26] ], however such proposals need to be further investigated.…”

An In Vitro Study on the Effects of Aromatic Hydrocarbons 1- Naphthol and Dibenz[a,h]anthracene in HepG2 Cells

“…Aromatic hydrocarbons are known to influence lipid metabolism (Kassotis et al, 2021). Hydroxylated aromatic hydrocarbon Tetra bromobisphenol A is reported to induce accumalation of oil droplets in human mesenchymal stem cells (Kakutani et al, 2018). The highly non polar Polycyclic aromatic hydrocarbon tetrachlorodibenzo-p-dioxin (TCDD) however, downregulated lipogenesis.…”

Obesogens: How They Are Identified and Molecular Mechanisms Underlying Their Action

“…In contrast, when TCDD was administered alone, it inhibited the differentiation process and PPARγ mRNA expression. However, when dually administered, TBBPA overrode TCDD’s inhibitory properties ( 124 ). Interestingly, TBBPA also increased the number of lipid droplets in hMSCs that differentiated into osteoblasts.…”

“…Interestingly, TBBPA also increased the number of lipid droplets in hMSCs that differentiated into osteoblasts. While lipids in the bone marrow are an essential component of bone health, too many lipids can result in the impairment of stem and progenitor cell function ( 124 , 125 ).…”