Mechanisms of toxicity caused by bisphenol analogs in human in vitro cell models

Abstract

Bisphenol analogs, structurally similar to bisphenol A (BPA), are widely used in various industries as a safer alternative to BPA. However, these alternatives also present risks, such as inflammation and potential connections to chronic diseases like cancer and diabetes, highlighting the need for further research into their toxicity mechanisms. Building on our previous cytotoxicity research, this study delves into the mechanisms of toxicity associated with bisphenol analogs (bisphenol AF, bisphenol AP, bisphenol E, and bisphenol P) on human in vitro cell models (HepaRG, Caco-2, HMC3, and HMEC-1). In this study, we assessed the impact of these compounds on key cellular stress markers: reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), and mitochondrial calcium levels. Results revealed dose-dependent increases in oxidative stress and decrease in mitochondrial membrane potential (ΔΨm), with Caco-2 cells (enterocytes) exhibiting the highest sensitivity, indicating tissue-specific vulnerability. Notably, bisphenol AF, bisphenol AP and bisphenol P were identified as the most potent analogs in inducing ROS, affecting mitochondrial integrity and calcium homeostasis among all cell models. This research highlights the importance of understanding analog-specific and cell-specific responses to bisphenol compounds, providing a foundation for improved regulatory strategies to mitigate health risks associated with their exposure.