The Short-Term Exposure to SDHI Fungicides Boscalid and Bixafen Induces a Mitochondrial Dysfunction in Selective Human Cell Lines

Abstract

Fungicides are used to suppress the growth of fungi for crop protection. The most widely used fungicides are succinate dehydrogenase inhibitors (SDHIs) that act by blocking succinate dehydrogenase, the complex II of the mitochondrial electron transport chain. As recent reports suggested that SDHI-fungicides could not be selective for their fungi targets, we tested the mitochondrial function of human cells (Peripheral Blood Mononuclear Cells or PBMCs, HepG2 liver cells, and BJ-fibroblasts) after exposure for a short time to Boscalid and Bixafen, the two most used SDHIs. Electron Paramagnetic Resonance (EPR) spectroscopy was used to assess the oxygen consumption rate (OCR) and the level of mitochondrial superoxide radical. The OCR was significantly decreased in the three cell lines after exposure to both SDHIs. The level of mitochondrial superoxide increased in HepG2 after Boscalid and Bixafen exposure. In BJ-fibroblasts, mitochondrial superoxide was increased after Bixafen exposure, but not after Boscalid. No significant increase in mitochondrial superoxide was observed in PBMCs. Flow cytometry revealed an increase in the number of early apoptotic cells in HepG2 exposed to both SDHIs, but not in PBMCs and BJ-fibroblasts, results consistent with the high level of mitochondrial superoxide found in HepG2 cells after exposure. In conclusion, short-term exposure to Boscalid and Bixafen induces a mitochondrial dysfunction in human cells.

Assessment of Mitochondrial Function in the AmE‐711 Honey Bee Cell Line: Boscalid and Pyraclostrobin Effects

“…The authors suggest that the observed differential sensitivity to boscalid may have been driven by the differences in antioxidant capacity of the cell lines and the differences in mitochondrial content (e.g., hepatoma cells have very high numbers of mitochondria). This explanation was supported by the finding of higher levels of mitochondrial superoxide in HepG2 cells exposed to boscalid (d'Hose et al, 2021), and is congruent with the findings of Bénit et al (2019) showing that effects of SDH inhibitors are more pronounced in cell types that are not well equipped to counter oxidative insults, such as cells with impaired superoxide dismutase signaling resulting from defective nuclear factor erythroid 2–related factor 2 translocation.…”

“…For example, Karakayali et al (2021) reported reduced viability for the mouse neuroblastoma cell line N2a after 24 to 48‐h exposure to boscalid (EC50 = 55.66 μM). d'Hose et al (2021) reported an increase in apoptosis in HepG2 cells exposed to 1 μM boscalid for 2 h, but not in peripheral blood mononuclear cells and BJ fibroblasts. The authors suggest that the observed differential sensitivity to boscalid may have been driven by the differences in antioxidant capacity of the cell lines and the differences in mitochondrial content (e.g., hepatoma cells have very high numbers of mitochondria).…”

“…Boscalid (2‐chloro‐ N ‐[2‐(4‐chlorophenyl)phenyl]pyridine‐3‐carboxamide) and pyraclostrobin (methyl N ‐[2‐[[1‐(4‐chlorophenyl)pyrazol‐3‐yl]oxymethyl]phenyl]‐ N ‐methoxycarbamate) were selected as test chemicals because they have been shown to act as mitochondrial stressors in mammalian cells (d'Hose et al, 2021; Luz et al, 2018; van der Stel et al, 2020). Boscalid is a Group 7 carboxamide that targets fungal succinate dehydrogenase (SDH)/respiratory complex II (CII; reviewed in Avenot & Michailides, 2010).…”

Analysis of Pesticide Residues on Fruit Using Swab Spray Ionization Mass Spectrometry

“…According to the Food and Agriculture Organization (FAO) of the United Nations [ 23 ], global pesticide usage in agriculture reached 2.7 million tons of active ingredients in 2020. Analytical methods for the detection of pesticide residues on food are indispensable for ensuring food safety at all steps, from the producers to the consumers, therefore avoiding exposure and toxic effects to humans [ 24 , 25 , 26 ]. Furthermore, the global pesticide usage causes environmental impacts, including the transformation of known pesticides into hitherto unknown agents [ 27 ].…”

Novel Coumarin 7-Carboxamide/Sulfonamide Derivatives as Potential Fungicidal Agents: Design, Synthesis, and Biological Evaluation

“…Carboxamide fungicides are a kind of ancient fungicides, the number of which occupies a large proportion. Bayer, BASF, Syngenta, and other companies have successively developed novel varieties of commercial amide fungicides, such as sopyrazam, fluopyram, and bixafen [ 18 , 19 , 20 ]. Sulfonamide compounds have various physiological activities and are widely used in pesticides.…”