Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid

The fungicides strobilurins and succinate dehydrogenase inhibitors (SDHIs) are blockers of the electron transport chain (ETC) in fungi. Here, we show that the exposure for 24 h to kresoxym-methyl, a fungicide from the class of strobilurins, alters the mitochondrial respiration in human HepG2 hepatoc...

Full description

Saved in:
Bibliographic Details
Main Authors: Yasmine Vandensande, Mélina Carbone, Barbara Mathieu, Bernard Gallez
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Redox Report
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2024.2424677
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846138658300624896
author Yasmine Vandensande
Mélina Carbone
Barbara Mathieu
Bernard Gallez
author_facet Yasmine Vandensande
Mélina Carbone
Barbara Mathieu
Bernard Gallez
author_sort Yasmine Vandensande
collection DOAJ
description The fungicides strobilurins and succinate dehydrogenase inhibitors (SDHIs) are blockers of the electron transport chain (ETC) in fungi. Here, we show that the exposure for 24 h to kresoxym-methyl, a fungicide from the class of strobilurins, alters the mitochondrial respiration in human HepG2 hepatocytes. In addition, we demonstrate an increase in production of mitochondrial superoxide radical anion, a reduction in ATP level, a decrease in the ratio reduced/oxidized glutathione and a decrease in cell viability (assessed by the LDH assay, Presto Blue assay, and Crystal Violet assay). As kresoxym-methyl is associated to boscalid (SDHI) in commercial formulations, we analyzed a potential exacerbation of the induced mitochondrial dysfunction for this combination. For the highest dose at which kresoxym-methyl (5 µM) and boscalid (0.5 µM) did not induce changes in mitochondrial function when used separately, in contrast, when both fungicides were used in combination at the same concentration, we observed a significant alteration of the mitochondrial function of hepatocytes: there was a decrease in oxygen consumption rate, in the ATP level. In addition, the level of mitochondrial superoxide radical anion was increased leading to a decrease in the ratio reduced/oxidized glutathione, and an increase in viability.
format Article
id doaj-art-280dbd9a7e6f4c1d88bf1a41cc6d1d0b
institution Kabale University
issn 1351-0002
1743-2928
language English
publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Redox Report
spelling doaj-art-280dbd9a7e6f4c1d88bf1a41cc6d1d0b2024-12-07T06:20:31ZengTaylor & Francis GroupRedox Report1351-00021743-29282024-12-0129110.1080/13510002.2024.2424677Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalidYasmine Vandensande0Mélina Carbone1Barbara Mathieu2Bernard Gallez3Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, BelgiumBiomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, BelgiumBiomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, BelgiumBiomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, BelgiumThe fungicides strobilurins and succinate dehydrogenase inhibitors (SDHIs) are blockers of the electron transport chain (ETC) in fungi. Here, we show that the exposure for 24 h to kresoxym-methyl, a fungicide from the class of strobilurins, alters the mitochondrial respiration in human HepG2 hepatocytes. In addition, we demonstrate an increase in production of mitochondrial superoxide radical anion, a reduction in ATP level, a decrease in the ratio reduced/oxidized glutathione and a decrease in cell viability (assessed by the LDH assay, Presto Blue assay, and Crystal Violet assay). As kresoxym-methyl is associated to boscalid (SDHI) in commercial formulations, we analyzed a potential exacerbation of the induced mitochondrial dysfunction for this combination. For the highest dose at which kresoxym-methyl (5 µM) and boscalid (0.5 µM) did not induce changes in mitochondrial function when used separately, in contrast, when both fungicides were used in combination at the same concentration, we observed a significant alteration of the mitochondrial function of hepatocytes: there was a decrease in oxygen consumption rate, in the ATP level. In addition, the level of mitochondrial superoxide radical anion was increased leading to a decrease in the ratio reduced/oxidized glutathione, and an increase in viability.https://www.tandfonline.com/doi/10.1080/13510002.2024.2424677Fungicidesmitochondrial functionElectron Paramagnetic Resonance (EPR)cocktail effectstrobilurinSDHI
spellingShingle Yasmine Vandensande
Mélina Carbone
Barbara Mathieu
Bernard Gallez
Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid
Redox Report
Fungicides
mitochondrial function
Electron Paramagnetic Resonance (EPR)
cocktail effect
strobilurin
SDHI
title Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid
title_full Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid
title_fullStr Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid
title_full_unstemmed Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid
title_short Mitochondrial dysfunction induced in human hepatic HepG2 cells exposed to the fungicide kresoxim-methyl and to a mixture kresoxim-methyl/boscalid
title_sort mitochondrial dysfunction induced in human hepatic hepg2 cells exposed to the fungicide kresoxim methyl and to a mixture kresoxim methyl boscalid
topic Fungicides
mitochondrial function
Electron Paramagnetic Resonance (EPR)
cocktail effect
strobilurin
SDHI
url https://www.tandfonline.com/doi/10.1080/13510002.2024.2424677
work_keys_str_mv AT yasminevandensande mitochondrialdysfunctioninducedinhumanhepatichepg2cellsexposedtothefungicidekresoximmethylandtoamixturekresoximmethylboscalid
AT melinacarbone mitochondrialdysfunctioninducedinhumanhepatichepg2cellsexposedtothefungicidekresoximmethylandtoamixturekresoximmethylboscalid
AT barbaramathieu mitochondrialdysfunctioninducedinhumanhepatichepg2cellsexposedtothefungicidekresoximmethylandtoamixturekresoximmethylboscalid
AT bernardgallez mitochondrialdysfunctioninducedinhumanhepatichepg2cellsexposedtothefungicidekresoximmethylandtoamixturekresoximmethylboscalid