4.7 Review

Indirect mediators of systemic health outcomes following nanoparticle inhalation exposure

Journal

PHARMACOLOGY & THERAPEUTICS
Volume 235, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2022.108120

Keywords

Nanoparticles; Nanotubes; Nanomaterials; Inhalation toxicology; Neurotoxicology; Peptidomics

Funding

  1. National Institute for Occupational Safety and Health, United States [OH010495, NIOSH/NTRC 939ZXFL]
  2. National Institute of Environmental Health Sciences, United States [ES014639]
  3. National Institute on Aging, United States [AG070776]

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The field of nanoscience has revealed the wide diversity of nano-scale particulates from natural and anthropogenic sources, raising concerns about their impacts on human health. Inhalation is the primary route of entry, depositing nanoparticles deep into the lungs and potentially affecting organs like the cardiovascular system and brain. Research has shown that the translocation of nanoparticles from the lungs to the circulation, as well as the release of molecules from the lungs into the bloodstream, can lead to various systemic outcomes.
The growing field of nanoscience has shed light on the wide diversity of natural and anthropogenic sources of nano-scale particulates, raising concern as to their impacts on human health. Inhalation is the most robust route of entry, with nanoparticles (NPs) evading mucociliary clearance and depositing deep into the alveolar region. Yet, impacts from inhaled NPs are evident far outside the lung, particularly on the cardiovascular system and highly vascularized organs like the brain. Peripheral effects are partly explained by the translocation of some NPs from the lung into the circulation; however, other NPs largely confined to the lung are still accompanied by systemic outcomes. Omic research has only just begun to inform on the complex myriad of molecules released from the lung to the blood as byproducts of pulmonary pathology. These indirect mediators are diverse in their molecular make-up and activity in the periphery. The present review examines systemic outcomes attributed to pulmonary NP exposure and what is known about indirect pathological mediators released from the lung into the circulation. Further focus was directed to outcomes in the brain, a highly vascularized region susceptible to acute and longer-term outcomes. Findings here support the need for big-data toxicological studies to understand what drives these health outcomes and better predict, circumvent, and treat the potential health impacts arising from NP exposure scenarios. (C) 2022 Elsevier Inc. All rights reserved.

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