Determination of microplastic-induced sublethal phenotypic changes in two human hepatocyte models using high-content analysis

• Grant number: 22/07854-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcelo Bispo de Jesus
• Grantee: Mariana Rodrigues da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The uncontrollable accumulation of plastics in the environment is a growing global problem. Micro- and nanoplastics (MPs and NPs), derived from the degradation of plastic waste or intentionally produced, are found in air, water, and various foods, with polystyrene (PS) being one of the most common. It is estimated that we ingest up to 5 g of these particles weekly, which is concerning considering that MPs <150 m and NP can cross our intestinal barrier and accumulate in multiple organs, mainly the liver. However, studies evaluating the hepatotoxic potential of MPs and NPs in a predictive manner for human health and at environmentally relevant concentrations are insufficient. Therefore, we propose investigating sublethal hepatotoxic changes induced by PS MPs at relevant concentrations. Rather than using animal models, which have limitations of time, prediction, cost, and ethical issues, we decided to assess the toxic effects in two relevant human hepatocyte lineages using two high-content analysis/screening approaches, one oriented towards hepatotoxicity and another unbiased. The phenotypic profile is determined using morphological traits to identify and predict events associated with hepatotoxicity, assessing subtle changes in a detailed cell-by-cell analysis. This study can provide robust and predictive results that can contribute to a better understanding of the hepatotoxic potential of PS-NPs and MPs for humans and provide data for decision making based on the molecular and cellular mechanisms underlying the hepatotoxicity of microplastics.