Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction

Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remai...

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Main Authors: Peilin Li, Daisuke Miyamoto, Tomohiko Adachi, Takanobu Hara, Akihiko Soyama, Hajime Matsushima, Hajime Imamura, Kengo Kanetaka, Weili Gu, Susumu Eguchi
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324014064
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author Peilin Li
Daisuke Miyamoto
Tomohiko Adachi
Takanobu Hara
Akihiko Soyama
Hajime Matsushima
Hajime Imamura
Kengo Kanetaka
Weili Gu
Susumu Eguchi
author_facet Peilin Li
Daisuke Miyamoto
Tomohiko Adachi
Takanobu Hara
Akihiko Soyama
Hajime Matsushima
Hajime Imamura
Kengo Kanetaka
Weili Gu
Susumu Eguchi
author_sort Peilin Li
collection DOAJ
description Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remains unclear. Recent studies have demonstrated that PS-MPs cause lipid and bile acid metabolism disorders. The human hepatobiliary organoids (HBOs) regenerated from chemically induced liver progenitor cells converted by mature hepatocytes and the bile duct provides a bioengineering model for liver disease and hepatic metabolism. Approach & Results: Exposure of HBOs to PS-MPs with a diameter of 1 µm for 48 h causes hepatotoxicity, hepatocyte damage, and changes in bile acid metabolism. PS-MPs could be accumulated into the bile ducts of HBOs, which can be promoted by ursodeoxycholic acid, increasing bile flow and volume by activating the bile transporter of BSEP in a dose-dependent manner along with MRP-2. The accumulation of PS-MPs in the bile duct was able to be inhibited by the bile transporter inhibitor of troglitazone that could inhibit the transporters of BSEP and MRP-2, which increased the hepatotoxicity caused by PS-MPs. Conclusions: This study provides insights into the metabolic pathways of PS-MPs in the liver and suggests potential therapeutic strategies to reduce MP-induced liver damage.
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spelling doaj-art-d4e089fca848452998fadf26ca9e2d9c2025-08-20T02:20:56ZengElsevierEcotoxicology and Environmental Safety0147-65132024-12-0128811733010.1016/j.ecoenv.2024.117330Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extractionPeilin Li0Daisuke Miyamoto1Tomohiko Adachi2Takanobu Hara3Akihiko Soyama4Hajime Matsushima5Hajime Imamura6Kengo Kanetaka7Weili Gu8Susumu Eguchi9Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, Japan; Department of Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, JapanDepartment of Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, Japan; Corresponding author.Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remains unclear. Recent studies have demonstrated that PS-MPs cause lipid and bile acid metabolism disorders. The human hepatobiliary organoids (HBOs) regenerated from chemically induced liver progenitor cells converted by mature hepatocytes and the bile duct provides a bioengineering model for liver disease and hepatic metabolism. Approach & Results: Exposure of HBOs to PS-MPs with a diameter of 1 µm for 48 h causes hepatotoxicity, hepatocyte damage, and changes in bile acid metabolism. PS-MPs could be accumulated into the bile ducts of HBOs, which can be promoted by ursodeoxycholic acid, increasing bile flow and volume by activating the bile transporter of BSEP in a dose-dependent manner along with MRP-2. The accumulation of PS-MPs in the bile duct was able to be inhibited by the bile transporter inhibitor of troglitazone that could inhibit the transporters of BSEP and MRP-2, which increased the hepatotoxicity caused by PS-MPs. Conclusions: This study provides insights into the metabolic pathways of PS-MPs in the liver and suggests potential therapeutic strategies to reduce MP-induced liver damage.http://www.sciencedirect.com/science/article/pii/S0147651324014064MicroplasticHepatotoxicityChemical induced progenitor cellsOrganoidbile metabolism
spellingShingle Peilin Li
Daisuke Miyamoto
Tomohiko Adachi
Takanobu Hara
Akihiko Soyama
Hajime Matsushima
Hajime Imamura
Kengo Kanetaka
Weili Gu
Susumu Eguchi
Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction
Ecotoxicology and Environmental Safety
Microplastic
Hepatotoxicity
Chemical induced progenitor cells
Organoid
bile metabolism
title Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction
title_full Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction
title_fullStr Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction
title_full_unstemmed Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction
title_short Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction
title_sort mitigation of polystyrene microplastic induced hepatotoxicity in human hepatobiliary organoids through bile extraction
topic Microplastic
Hepatotoxicity
Chemical induced progenitor cells
Organoid
bile metabolism
url http://www.sciencedirect.com/science/article/pii/S0147651324014064
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