The dithiocarbamate pesticides maneb and mancozeb disturb the metabolism of lipids and xenobiotics in an in vitro model of metabolic dysfunction-associated steatotic liver disease.
Saved in:
| Title: | The dithiocarbamate pesticides maneb and mancozeb disturb the metabolism of lipids and xenobiotics in an in vitro model of metabolic dysfunction-associated steatotic liver disease. |
|---|---|
| Authors: | Petitjean, Kilian1 (AUTHOR), Dicara, Giovanna1 (AUTHOR), Bristeau, Sébastien2 (AUTHOR), Coppens-Exandier, Hugo1 (AUTHOR), Amalric, Laurence2 (AUTHOR), Baran, Nicole2 (AUTHOR), Savary, Camille C.3 (AUTHOR), Corlu, Anne1 (AUTHOR), Loyer, Pascal1 (AUTHOR), Fromenty, Bernard1 (AUTHOR) bernard.fromenty@inserm.fr |
| Source: | Environmental Toxicology & Pharmacology. Sep2025, Vol. 118, pN.PAG-N.PAG. 1p. |
| Subject Terms: | *Pesticides, Mancozeb, Fatty liver, Hepatotoxicology, Low density lipoproteins, Metabolic disorders, Cytochrome P-450 |
| Abstract: | Pesticides are increasingly recognized to be hepatotoxic, but less is known about their toxicity in metabolic dysfunction-associated steatotic liver disease (MASLD). Herein, differentiated HepaRG cells cultured for 2 weeks without (-FA) or with (+FA) a mixture of fatty acids were treated with different pesticides, including maneb and mancozeb, during the same period. While maneb and mancozeb did not induce neutral lipid accumulation in -FA-HepaRG cells, they worsened steatosis in +FA-HepaRG cells. MnCl 2 treatment reproduced these effects. Maneb or MnCl 2 impaired very low-density lipoprotein (VLDL) secretion and increased fatty acid uptake. Zinc supplementation restored VLDL secretion, reduced fatty acid uptake, and prevented steatosis worsening in +FA-HepaRG cells treated with mancozeb or MnCl 2. Maneb, or MnCl 2, also reduced the mRNA expression and activity of several cytochromes P450 in +FA- and -FA-HepaRG cells. This was associated with impaired biotransformation of diazinon. These findings could have major pathophysiological consequences in dithiocarbamate-exposed individuals with MASLD. • Pesticide hepatotoxicity is understudied in the setting of obesity-related steatosis. • Maneb, mancozeb, or MnCl 2 worsens steatosis in HepaRG cells cultured with fatty acids. • This effect is associated with reduced VLDL secretion and increased fatty acid uptake. • Zinc supplementation prevents mancozeb or MnCl 2 -induced steatosis. • Maneb or MnCl 2 also impairs the activity of several cytochromes P450 in HepaRG cells. [ABSTRACT FROM AUTHOR] |
| Copyright of Environmental Toxicology & Pharmacology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | GreenFILE |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: 8gh DbLabel: GreenFILE An: 187647635 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: The dithiocarbamate pesticides maneb and mancozeb disturb the metabolism of lipids and xenobiotics in an in vitro model of metabolic dysfunction-associated steatotic liver disease. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Petitjean%2C+Kilian%22">Petitjean, Kilian</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dicara%2C+Giovanna%22">Dicara, Giovanna</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bristeau%2C+Sébastien%22">Bristeau, Sébastien</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Coppens-Exandier%2C+Hugo%22">Coppens-Exandier, Hugo</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Amalric%2C+Laurence%22">Amalric, Laurence</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Baran%2C+Nicole%22">Baran, Nicole</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Savary%2C+Camille+C%2E%22">Savary, Camille C.</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Corlu%2C+Anne%22">Corlu, Anne</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Loyer%2C+Pascal%22">Loyer, Pascal</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fromenty%2C+Bernard%22">Fromenty, Bernard</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> bernard.fromenty@inserm.fr</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Environmental+Toxicology+%26+Pharmacology%22">Environmental Toxicology & Pharmacology</searchLink>. Sep2025, Vol. 118, pN.PAG-N.PAG. 1p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22Pesticides%22">Pesticides</searchLink><br /><searchLink fieldCode="DE" term="%22Mancozeb%22">Mancozeb</searchLink><br /><searchLink fieldCode="DE" term="%22Fatty+liver%22">Fatty liver</searchLink><br /><searchLink fieldCode="DE" term="%22Hepatotoxicology%22">Hepatotoxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Low+density+lipoproteins%22">Low density lipoproteins</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolic+disorders%22">Metabolic disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Cytochrome+P-450%22">Cytochrome P-450</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Pesticides are increasingly recognized to be hepatotoxic, but less is known about their toxicity in metabolic dysfunction-associated steatotic liver disease (MASLD). Herein, differentiated HepaRG cells cultured for 2 weeks without (-FA) or with (+FA) a mixture of fatty acids were treated with different pesticides, including maneb and mancozeb, during the same period. While maneb and mancozeb did not induce neutral lipid accumulation in -FA-HepaRG cells, they worsened steatosis in +FA-HepaRG cells. MnCl 2 treatment reproduced these effects. Maneb or MnCl 2 impaired very low-density lipoprotein (VLDL) secretion and increased fatty acid uptake. Zinc supplementation restored VLDL secretion, reduced fatty acid uptake, and prevented steatosis worsening in +FA-HepaRG cells treated with mancozeb or MnCl 2. Maneb, or MnCl 2, also reduced the mRNA expression and activity of several cytochromes P450 in +FA- and -FA-HepaRG cells. This was associated with impaired biotransformation of diazinon. These findings could have major pathophysiological consequences in dithiocarbamate-exposed individuals with MASLD. • Pesticide hepatotoxicity is understudied in the setting of obesity-related steatosis. • Maneb, mancozeb, or MnCl 2 worsens steatosis in HepaRG cells cultured with fatty acids. • This effect is associated with reduced VLDL secretion and increased fatty acid uptake. • Zinc supplementation prevents mancozeb or MnCl 2 -induced steatosis. • Maneb or MnCl 2 also impairs the activity of several cytochromes P450 in HepaRG cells. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Environmental Toxicology & Pharmacology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=8gh&AN=187647635 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.etap.2025.104773 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 1 StartPage: N.PAG Subjects: – SubjectFull: Pesticides Type: general – SubjectFull: Mancozeb Type: general – SubjectFull: Fatty liver Type: general – SubjectFull: Hepatotoxicology Type: general – SubjectFull: Low density lipoproteins Type: general – SubjectFull: Metabolic disorders Type: general – SubjectFull: Cytochrome P-450 Type: general Titles: – TitleFull: The dithiocarbamate pesticides maneb and mancozeb disturb the metabolism of lipids and xenobiotics in an in vitro model of metabolic dysfunction-associated steatotic liver disease. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Petitjean, Kilian – PersonEntity: Name: NameFull: Dicara, Giovanna – PersonEntity: Name: NameFull: Bristeau, Sébastien – PersonEntity: Name: NameFull: Coppens-Exandier, Hugo – PersonEntity: Name: NameFull: Amalric, Laurence – PersonEntity: Name: NameFull: Baran, Nicole – PersonEntity: Name: NameFull: Savary, Camille C. – PersonEntity: Name: NameFull: Corlu, Anne – PersonEntity: Name: NameFull: Loyer, Pascal – PersonEntity: Name: NameFull: Fromenty, Bernard IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 09 Text: Sep2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 13826689 Numbering: – Type: volume Value: 118 Titles: – TitleFull: Environmental Toxicology & Pharmacology Type: main |
| ResultId | 1 |
