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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Polystyrene Microplastics Postpone APAP-Induced Liver Injury through Impeding Macrophage Polarization
Jing Liu1,2,3, Lecong Zhang1, Fang Xu1,3
1College of Eco-Environmental Engineering, Guizhou Minzu University, Guiyang 550025, China.
Abstract:
Polystyrene microplastics (PS MPs) are micrometer-scale items degraded from plastics and have been detected in various organisms. PS MPs have been identified as causing cognitive, cardiac, intestinal, and hepatic damage. However, their role in liver regeneration under drug-induced liver injury remains unknown. Thus, the current study aims to evaluate the impact of PS MPs on liver repair during APAP hepatotoxicity. PS MPs pretreatment exacerbates mice mortality and hepatocyte apoptosis, suppresses hepatic cell proliferation, and disturbs the inflammatory response in the APAP-induced damage model. Further mechanism exploration uncovers that prior PS MPs administration is sufficient to recruit neutrophils and macrophages, which are necessary for tissue recovery in the acute liver injury model. However, the polarization capacity of macrophages to anti-inflammatory sub-type is significantly delayed in PS MPs plus APAP group compared to the single APAP group, which is the leading cause of tissue repair suppression. Overall, the current study supports a new insight to realize the toxicity of PS MPs in acute liver injury, which should be considered in health risk assessment.
Insights
Polystyrene microplastics (PS MPs) impair liver repair following acetaminophen (APAP) induced liver injury by delaying crucial macrophage polarization, increasing mortality and liver damage in mice.
Area of Science:
- Environmental toxicology
- Hepatology
- Immunology
Background:
- Polystyrene microplastics (PS MPs) are pervasive environmental contaminants found in numerous organisms.
- Previous research indicates PS MPs can cause damage to cognitive, cardiac, intestinal, and hepatic systems.
- The specific impact of PS MPs on liver regeneration during drug-induced liver injury (DILI) is not well understood.
Purpose of the Study:
- To investigate the effects of PS MPs on liver repair mechanisms in a mouse model of acetaminophen (APAP)-induced liver injury.
- To elucidate the underlying cellular and molecular mechanisms by which PS MPs influence liver regeneration.
Main Methods:
- Mice were pretreated with PS MPs before APAP administration to induce acute liver injury.
- Evaluated parameters included mortality, hepatocyte apoptosis, cell proliferation, and inflammatory responses.
- Immune cell recruitment and macrophage polarization were analyzed using flow cytometry and histological assessments.
Main Results:
- PS MPs pretreatment significantly increased mortality and hepatocyte apoptosis in APAP-induced liver injury.
- Exposure to PS MPs suppressed hepatic cell proliferation and altered the inflammatory milieu.
- While PS MPs recruited neutrophils and macrophages, they delayed the polarization of macrophages towards an anti-inflammatory phenotype, hindering tissue repair.
Conclusions:
- Polystyrene microplastics exacerbate APAP-induced hepatotoxicity and impede liver regeneration.
- Delayed macrophage polarization is identified as a key mechanism underlying PS MP-induced suppression of liver repair.
- These findings highlight the potential health risks associated with PS MP exposure, particularly in individuals with compromised liver function, necessitating their consideration in health risk assessments.
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