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Review
. 2023 Jun 10;2(3):95-106.
doi: 10.1016/j.eehl.2023.06.001. eCollection 2023 Sep.

The bio-distribution, clearance pathways, and toxicity mechanisms of ambient ultrafine particles

Dongyang Han  1 , Renjie Chen  1 , Haidong Kan  1 , Yanyi Xu  1
Affiliations
Review

The bio-distribution, clearance pathways, and toxicity mechanisms of ambient ultrafine particles

Dongyang Han et al. Eco Environ Health. .

Abstract

Ambient particles severely threaten human health worldwide. Compared to larger particles, ultrafine particles (UFPs) are highly concentrated in ambient environments, have a larger specific surface area, and are retained for a longer time in the lung. Recent studies have found that they can be transported into various extra-pulmonary organs by crossing the air-blood barrier (ABB). Therefore, to understand the adverse effects of UFPs, it is crucial to thoroughly investigate their bio-distribution and clearance pathways in vivo after inhalation, as well as their toxicological mechanisms. This review highlights emerging evidence on the bio-distribution of UFPs in pulmonary and extra-pulmonary organs. It explores how UFPs penetrate the ABB, the blood-brain barrier (BBB), and the placental barrier (PB) and subsequently undergo clearance by the liver, kidney, or intestine. In addition, the potential underlying toxicological mechanisms of UFPs are summarized, providing fundamental insights into how UFPs induce adverse health effects.

Keywords: Ambient ultrafine particles; Bio-distribution of particles; Clearance pathways; Toxicity mechanisms.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Bio-distribution and clearance pathways of ambient UFPs in the body. After inhaling via the respiratory system, UFPs are first deposited in the lung, and then they may penetrate the ABB and be deposited in extra-pulmonary organs such as the heart, liver, kidney, and spleen through blood circulation. In addition, UFPs in the circulation may also penetrate the BBB and PB, leading to deposition in the brain and placenta. It is worth noting that there is also a nasal olfactory pathway regarding the deposition of UFPs in the brain. The main clearance pathway of UFPs in the body is by the kidney, with the vast majority of particles excreted in urine. In addition, clearance by liver and gastrointestine also plays an important role in some cases. The lymphatic circulation also plays an essential role in the clearance process of UFPs in vivo.
Fig. 2
Fig. 2
The potential toxicity mechanisms of ambient UFPs. UFPs may induce toxicity mainly through pathways including the introduction of cell damage (such as cell membrane disruption marked by LDH extravasation, endoplasmic reticulum stress, cell apoptosis, IP3R-mediated mitochondrial dysfunction and lysosomal damage, STEAP3/DMT1-mediated ferroptosis), oxidative stress and inflammatory response (such as Nrf2-mediated oxidative stress, NF-κB and AP-1-mediated inflammatory responses), and DNA damage (such as PI3K/AKT/FOXO3a-mediated double-strand breakage and HIF-1α/miR-210/Rad52-mediated DNA repair defect).
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