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

Autor: Vandensande Y; Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, Belgium., Carbone M; Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, Belgium., Mathieu B; Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, Belgium., Gallez B; Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Brussels, Belgium.
Jazyk: angličtina
Zdroj: Redox report : communications in free radical research [Redox Rep] 2024 Dec; Vol. 29 (1), pp. 2424677. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1080/13510002.2024.2424677
Abstrakt: 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.
Databáze: MEDLINE