The alternative analog plasticizer BPS displays similar phenotypic and metabolomic responses to BPA in HepG2 and INS-1E cells

Author(s)

Azevedo, L. Ferreira ; Masiero, M. Miguel ; Cherkaoui, S. ; Carneiro, M. F. Hornos ; Jr, F. Barbosa ; Zamboni, N.

• Document type: Journal article
• Source: Food and Chemical Toxicology; v. 167, p. 14-pg., 2022-07-12.

Abstract

Bisphenols A (BPA) and S (BPS) are endocrine-disrupting chemicals that affect energy metabolism, leading to impairment of glucose and lipid homeostasis. We aimed at identifying metabolic pathways regulated by both compounds in human liver cells and rat pancreatic beta-cells that could impair energy homeostasis regulation. We assessed the effects on growth, proliferation, and viability of hepatocarcinoma (HepG2) and insulinoma (INS-1E) cells exposed to either BPA or BPS in a full range concentration between 0.001 and 100 mu M. Both the dose and duration of exposure caused a differential response on growth and viability of both cells. Effects were more pronounced on HepG2, as these cells exhibited non-linear dose-responses following exposure to xenobiotics. For INS-1E, effect was observed only at the highest concentration. In addition, we profiled their intracellular state by untargeted metabolomics at 24, 48, and 72 h of exposure. This analysis revealed time-and dose-dependently molecular changes for HepG2 and INS-1E that were similar between BPA and BPS. Both increased levels of in-flammatory mediators, such as metabolites pertaining to linolenic and linoleic acid metabolic pathway. In summary, this study shows that BPS also disrupts molecular functions in cells that regulate energy homeostasis, displaying similar but less pronounced responses than BPA. (AU)

• FAPESP's process: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health
• Grantee: Fernando Barbosa Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/10456-0 - Evaluation of protein expression and biochemical parameters related to diabetes mellitus type II and dyslipidemias in animals exposed to the contaminants bisphenol A and S
• Grantee: Lara Ferreira Azevedo
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/19554-0 - Assessment of mechanisms associated with energy homeostasis disruption after bisphenol A or S exposures through untargeted metabolomics
• Grantee: Lara Ferreira Azevedo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)