Deciphering the key events of micro- and nanoplastics toxicity triggered in skin to establish the adverse outcome pathway (AOP)

Overview

Project Summary

Plastic-based products are ubiquitous due to their tremendous utility in our daily lives. However, the limited biodegradable nature of plastics, especially micro- and nanoplastics (MPs/NPs), has recently raised global pollution concerns. These anthropogenic pollutants, currently widespread in the oceans, freshwater bodies, land or even present in food, are either manufactured specifically in the small size range for various commercial applications or formed due to fragmentation of macroplastics in the environment. The biological effects of MPs and NPs on aquatic organisms are well documented but their impacts on the mammalian system have not been deeply investigated and data on the impact on the human body at subcellular or molecular levels is scarce. In particular, the penetration of these particles through the skin epithelia and their effect on skin health has not been examined thoroughly. Therefore, going behind the state of the art, this project aims to elucidate the potential pathological events triggered by different MPs/NPs on skin with focus on oxidative and inflammatory damages, as well as aging-related events, at different levels of biological complexity (molecular, cellular and organ levels). Ultimately, this proposal will allow to identify the adverse outcome pathway (AOP) triggered by MPs/NPs exposome at the skin level.

Main Goals

The main goal of this project is to disclose the toxicity pathways triggered by microplastics (MPs) and nanoplastics (NPs) at the human skin level. To accomplish this, the effect of MPs/NPs exposome will be investigated at different levels of biological complexity, including organelles, cells representative of the epidermis and dermis as well as reconstructed human epidermis.

Specifically:

1) different types of MPs and NPs will be used, in particular polypropylene (PP), polyethylene (PE), polystyrene (PS) and polymethylmethacrylate (PMMA) particles;

2) different skin cells comprehending the epidermis (keratinocytes) and dermis (fibroblasts and macrophages), will be screened for toxicity triggered by the selected MPs and NPs; 

3) cellular and organelle key events affected by MPs/NPs skin exposome will be disclosed, with focus on oxidative and inflammatory damages, as well as senescence- and other aging-related events, namely generation of reactive oxygen species (ROS), release of pro-inflammatory mediators, activation of matrix metalloproteinases, DNA damage, endoplasmic reticulum stress, mitochondrial dysfunction, lysosome disruption and apoptosis resistance;

4) the most relevant key events triggered by MPs/NPs exposome will be confirmed at an organ level using Reconstructed Human Epidermis.

Hopefully, we expect to match MP/NPs toxicity endpoints with key events in order to better establish an AOP evoked by this specific exposome on the skin.

Project Details