# Subcytotoxic Exposure to Avobenzone and Ethylhexyl Salicylate Induces microRNA Modulation and Stress-Responsive PI3K/AKT and MAPK Signaling in Differentiated SH-SY5Y Cells

## TL;DR

This study shows that low doses of avobenzone and ethylhexyl salicylate, common UV filters, can trigger stress-related signaling in brain-like cells, suggesting potential effects on the nervous system.

## Contribution

The study reveals novel stress-related molecular responses in neuroblastoma cells exposed to subcytotoxic UV filters, linking them to PI3K/AKT and MAPK signaling pathways.

## Key findings

- Subcytotoxic concentrations of AVO and EHS modulate miR-200a-3p and miR-29b-3p in SH-SY5Y cells.
- Phosphorylation of AKT and ERK increases, indicating activation of PI3K/AKT and MAPK/ERK stress pathways.
- Exposure leads to an increased Bax/Bcl-2 ratio, suggesting pro-apoptotic signaling.

## Abstract

Avobenzone (AVO) and ethylhexyl salicylate (EHS) are widely used organic UV filters with distinct photochemical properties and reported biological effects. Experimental and predictive evidence suggests that some lipophilic UV filters may reach systemic circulation and potentially cross the blood–brain barrier (BBB), raising concerns about possible central nervous system effects, although direct evidence for AVO and EHS remains limited. This study evaluated the effects of subcytotoxic concentrations (0.01–1 µM) of AVO and EHS on differentiated SH-SY5Y human neuroblastoma cells, focusing on early stress-related molecular responses. Cell viability and reactive oxygen species production were not significantly affected at any tested concentration. Integrated analyses of microRNA, gene, and protein expression revealed modest and variable modulation of miR-200a-3p and miR-29b-3p. Western blot analysis showed increased phosphorylation of AKT and ERK, no significant changes in mTOR activation, and an increased Bax/Bcl-2 ratio. Overall, these findings indicate that AVO and EHS trigger an early stress-adaptive response involving PI3K/AKT and MAPK/ERK signaling and modulation of apoptosis-related pathways. Such responses reflect a dynamic balance between cellular adaptation and pro-apoptotic signaling, which may become relevant under prolonged or higher-intensity exposure conditions.