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bioRxiv · 10.1101/2023.10.24.563735

Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress

Gettings, S. M.·Timbury, W.·Dmochowska, A.·Sharma, R.·MacKenzie, L. E.·Miquelard-Garnier, G.·Bourbia, N.
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Abstract

The objective of this investigation was to evaluate the influence of micro- and nanoplastic particles composed of polyethylene terephthalate (PET), a significant contributor to plastic pollution, on human brain vascular pericytes. Specifically, we delved into their impact on mitochondrial functionality, oxidative stress, and the expression of genes associated with oxidative stress and ferroptosis. Our findings demonstrate that the exposure of a monoculture of human brain vascular pericytes to PET particles in vitro at a concentration of 50 ppm for a duration of 6 days did not elicit oxidative stress. Notably, we observed an augmentation in various aspects of mitochondrial respiration, including extracellular acidification, proton pump leakage, maximal respiration, spare respiratory capacity, and ATP production in pericytes subjected to PET particles. Furthermore, there were no statistically significant alterations in mitochondrial DNA copy number, or the expression of genes linked to oxidative stress and ferroptosis. These outcomes suggest that, at a concentration of 50 parts per million (ppm) and for 6 days exposure, PET particles do not induce oxidative stress in human brain vascular pericytes. Instead, they seem to incite a potential mitochondrial hormesis, also named mitohormesis, response, which seemingly enhances mitochondrial function. Further investigations are warranted to explore the stages of mitohormesis and the potential consequences of plastics on the integrity of the blood-brain barrier and intercellular interactions. This research contributes to our comprehension of the potential repercussions of nanoplastic pollution on human health and underscores the imperative need for ongoing examinations into the exposure to plastic particles. Graphical Abstract (created with BioRender.com) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/563735v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@2ea981org.highwire.dtl.DTLVardef@17a7619org.highwire.dtl.DTLVardef@df661eorg.highwire.dtl.DTLVardef@a9518f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightO_LIFabrication of polyethylene terephthalate (PET) micro- and nanoplastics C_LIO_LIPET particles increase pericytes mitochondrial respiration functions C_LIO_LIPET particles increase pericytes extracellular acidification C_LIO_LIOxidative stress was not observed in pericytes subjected to PET particles C_LI

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Gettings, S. M., Timbury, W., Dmochowska, A., Sharma, R., MacKenzie, L. E., Miquelard-Garnier, G., Bourbia, N.. 2023-10-28. Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress. https://doi.org/10.1101/2023.10.24.563735

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