Tebuconazole induces ROS-dependent cardiac cell toxicity by activating DNA damage and mitochondrial apoptotic pathway

Othmène, Yosra Ben; Monceaux, Kévin; Karoui, Ahmed; Salem, Intidhar Ben; Belhadef, Anissa; Abid‐Essefi, Salwa; Lemaire, Christophe

doi:10.1016/j.ecoenv.2020.111040

Cited by 45 publications

(31 citation statements)

References 53 publications

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“…There are two principal apoptosis pathways: the extrinsic pathway and the intrinsic mitochondrial pathway [ 31 ], which is the key signaling pathway in the induction of apoptosis [ 32 ]. It has been reported that the loss of MMP is a typical phenomenon in mitochondrial-dependent apoptosis [ 33 ]. In this work, LGSP decreased the MMP of HeLa cells, indicating that LGSP-induced apoptosis may be through the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 99%

Lipophilic Grape Seed Proanthocyanidin Exerts Anti-Cervical Cancer Effects in HeLa Cells and a HeLa-Derived Xenograft Zebrafish Model

Zhang

Liu

et al. 2022

Antioxidants

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Lipophilic grape seed proanthocyanidin (LGSP) synthesized from GSP and lauric acid exhibits an excellent antioxidant and anti-inflammatory effect. However, its anti-cervical cancer activity is still unknown. In this study, the in vitro anti-cervical cancer activity of LGSP on HeLa cell lines was investigated by MTT assay, flow cytometry and Western blot analysis, and its effect was explored by a HeLa-derived xenograft zebrafish model. LGSP exhibited an excellent anti-proliferative effect on HeLa cells by increasing the level of reactive oxygen species, which further induced cell apoptosis and blocked cell cycle progression in the G2/M phase. LGSP-treated HeLa cells showed a reduction in mitochondrial membrane potential, upregulation of the Bax/Bcl-2 ratio, release of cytochrome c into the cytoplasm, and activation of cleaved caspase-9/3 and cleavage of PARP, thus indicating that LGSP induced apoptosis through the intrinsic mitochondrial/caspase-mediated pathway. In the zebrafish model, LGSP effectively suppressed the growth of a HeLa xenograft tumor. These data suggest that LGSP may be a good candidate for the prevention or treatment of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Lipophilic Grape Seed Proanthocyanidin Exerts Anti-Cervical Cancer Effects in HeLa Cells and a HeLa-Derived Xenograft Zebrafish Model

Zhang

Liu

et al. 2022

Antioxidants

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“…They also suggested that TEB might induce oxidative stress in cardiac cells via the mitochondrial apoptotic pathway due to the loss of mitochondrial transmembrane potential (ΔΨ m ), an increase in the Bax/Bcl-2 ratio, an activation of caspase-9 and caspase-3, a cleavage of poly (ADP-ribose) polymerase (PARP), and an increase in mitochondrial superoxide (measured by MitoSOX). However, when they treated cardiomyocytes with the ROS scavenger NAC, there was a decrease in TEB-induced DNA damage and activation of the mitochondrial pathway of apoptosis [ 161 ].…”

Section: Introductionmentioning

confidence: 99%

A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity

Sule

Condon

Gomes

2022

Oxidative Medicine and Cellular Longevity

215

102

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Pesticides are important chemicals or biological agents that deter or kill pests. The use of pesticides has continued to increase as it is still considered the most effective method to reduce pests and increase crop growth. However, pesticides have other consequences, including potential toxicity to humans and wildlife. Pesticides have been associated with increased risk of cardiovascular disease, cancer, and birth defects. Labels on pesticides also suggest limiting exposure to these hazardous chemicals. Based on experimental evidence, various types of pesticides all seem to have a common effect, the induction of oxidative stress in different cell types and animal models. Pesticide-induced oxidative stress is caused by both reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are associated with several diseases including cancer, inflammation, and cardiovascular and neurodegenerative diseases. ROS and RNS can activate at least five independent signaling pathways including mitochondrial-induced apoptosis. Limited in vitro studies also suggest that exogenous antioxidants can reduce or prevent the deleterious effects of pesticides.

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“…In agreement, chlorpyrifos has previously been shown to induce apoptosis on neuronal cells by disrupting mitochondrial function and ROS production (Lee et al, 2012; Singh et al, 2018). Similarly, paraquat and tebuconazole are known to induce mitochondrial superoxide production in mammalian cells (Ben Othmene et al, 2020; Mukhopadhyay et al, 2007). As can be seen in Figure 3b, the three mixtures based on typical UPM profiles among Bolivian farmers all significantly induced mitochondrial ROS production at the highest concentration (3.5–4.4‐fold, p <.0001) and probably because the composition of these mixtures were dominated by either chlorpyrifos (U1 and U2) or tebuconazole (U3).…”

Section: Resultsmentioning

confidence: 99%

In vitro cytotoxicity and genotoxicity of single and combined pesticides used by Bolivian farmers

Cuenca

Galvão

Endirlik

et al. 2021

Environ and Mol Mutagen

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We previously showed that farmers in Bolivia are exposed to many pesticides, some at elevated levels, and that this was associated with increased risk of genetic damage. To improve the understanding of possible mixture effects, the cytotoxicity and genotoxicity of pesticides were studied in vitro using human liver HepG2 cells. The studied pesticides were 2,4‐D, chlorpyrifos, cypermethrin, glyphosate, methamidophos, paraquat, profenofos, and tebuconazole. Three mixtures (U1, U2, and U3) were based on profiles of urinary pesticide metabolites and one mixture on the most frequently used pesticides (S1). The results showed that paraquat and methamidophos were the most cytotoxic pesticides (EC50 ≤0.3 mM). Paraquat, chlorpyrifos, tebuconazole, and the U1, U2, and U3 mixtures, which contained a large proportion of either chlorpyrifos or tebuconazole, significantly increased intracellular ROS levels. Most pesticides activated DNA damage signaling through proteins Chk1 and H2AX. Strongest responses were elicited by paraquat, profenofos, chlorpyrifos, cypermethrin, and the S1 mixture, which contained 25% paraquat. Comet assay revealed significant increases of DNA damage in response to paraquat, cypermethrin, and U2 and S1 mixtures, which contained high levels of cypermethrin and paraquat, respectively. In summary, we showed that the tested pesticides, alone or in mixtures, in general induced oxidative stress and that most pesticides, and especially paraquat and cypermethrin, were genotoxic in HepG2 cells. We could also show that mixtures dominated by these two pesticides displayed a marked genotoxic potency, which agreed with our previous population studies.

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Tebuconazole induces ROS-dependent cardiac cell toxicity by activating DNA damage and mitochondrial apoptotic pathway

Cited by 45 publications

References 53 publications

Lipophilic Grape Seed Proanthocyanidin Exerts Anti-Cervical Cancer Effects in HeLa Cells and a HeLa-Derived Xenograft Zebrafish Model

Lipophilic Grape Seed Proanthocyanidin Exerts Anti-Cervical Cancer Effects in HeLa Cells and a HeLa-Derived Xenograft Zebrafish Model

A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity

In vitro cytotoxicity and genotoxicity of single and combined pesticides used by Bolivian farmers

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