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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Elsevier
2024-12-01
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| 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. |
| format | Article |
| id | doaj-art-d4e089fca848452998fadf26ca9e2d9c |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| 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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