Gillings School researchers uncover new mechanisms of PFAS toxicity in liver cells

August 22, 2024

A recent study published in PubMed led by researchers in the Department of Environmental Sciences and Engineering at the Gillings Global School of Public Health revealed new insights into how per- and polyfluoroalkyl substances (PFAS) affect liver cells. This research highlights a novel mechanism involving extracellular vesicles (EVs) as mediators of PFAS liver toxicity. 

PFAS are a group of human-made chemicals that have been used in various industrial and consumer products, from firefighting foam to nonstick cookware, for decades. Their widespread use and persistence in the environment have raised significant public health concerns. In many parts of North Carolina, PFAS levels in drinking water exceed the Environmental Protection Agency’s health advisory levels, posing potential risks to the population.  

Human exposure to PFAS has been linked to various adverse health effects, including liver damage. However, the specific mechanisms underlying these effects are not fully understood. Extracellular vesicles are tiny particles released by cells that carry molecular signals, such as microRNAs, to other parts of the body, acting as messengers and influencing disease. 

The research team exposed HepG2 liver cells to a defined mixture of PFAS, including PFOS, PFOA and PFHxA, selected based on their prevalence in North Carolina’s water sources.  

They found that PFAS exposure increases the number of EVs released from liver cells. Moreover, these EVs carried microRNAs and PFAS chemical signatures, with altered microRNA profiles predicted to target pathways involved in liver fibrosis and cancer. 

This study was the first to evaluate EVs as mediators of PFAS liver toxicity. 

“Understanding how EVs mediate PFAS toxicity opens up new possibilities for assessing and mitigating the health risks associated with these contaminants,” said Dr. Celeste Carberry, a recent Gillings School graduate and the study’s first author. “Our findings suggest that EVs could serve as biomarkers for PFAS exposure, providing a new tool for evaluating environmental health risks.” 

The study’s results are significant not only for North Carolina but for communities worldwide facing PFAS contamination. By identifying EVs as novel responders to PFAS exposure, this work sets a foundation for future studies to leverage EVs in biomarker detection and the development of health interventions.  

Julia Rager, PhD, assistant professor in the Department of Environmental Sciences and Engineering added “By characterizing the molecular content of EVs, we can gain a deeper understanding of the cellular processes disrupted by PFAS. This knowledge sets an important foundation for future studies aiming to develop targeted interventions to protect public health.”