Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells

Zhang, Baoyan; Xu, Zhiping; Zhang, Yixi; Shao, Xusheng; Xu, Xiaoyong; Cheng, Jiaogao; Li, Zhong

doi:10.1016/j.pestbp.2015.01.019

Cited by 47 publications

(21 citation statements)

References 60 publications

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“…Similar metabolic modulations have been observed in other cell types as well as mitochondria31474849; in addition, depending on the mode of exposure, these modulations can lead to cell death484950. We assume that these effects on the mortality and concentration of spermatozoa are due to physiological disruptions because an increase in energetic metabolism could lead to oxidative injuries by generating reactive oxygen species, as previously confirmed for Fipronil384950. Although spermatozoa exhibit antioxidant defenses51, an overload of these defenses can lead to cell death, explaining the high mortality rate of spermatozoa in drones exposed to Fipronil.…”

Section: Resultssupporting

confidence: 81%

Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential

Kairo¹,

Provost

Tchamitchian³

et al. 2016

Sci Rep

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A species that requires sexual reproduction but cannot reproduce is doomed to extinction. The important increasing loss of species emphasizes the ecological significance of elucidating the effects of environmental stressors, such as pesticides, on reproduction. Despite its special reproductive behavior, the honey bee was selected as a relevant and integrative environmental model because of its constant and diverse exposure to many stressors due to foraging activity. The widely used insecticide Fipronil, the use of which is controversial because of its adverse effects on honey bees, was chosen to expose captive drones in hives via syrup contaminated at 0.1 μg/L and gathered by foragers. Such environmental exposure led to decreased spermatozoa concentration and sperm viability coupled with an increased sperm metabolic rate, resulting in drone fertility impairment. Subsequently, unexposed queens inseminated with such sperm exhibited fewer spermatozoa with lower viability in their spermatheca, leaving no doubt about the detrimental consequences for the reproductive potential of queens, which are key for colony sustainability. These findings suggest that pesticides could contribute to declining honey bee populations through fertility impairment, as exemplified by Fipronil. More broadly, reproductive disorders should be taken into consideration when investigating the decline of other species.

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Section: Resultssupporting

confidence: 81%

Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential

Kairo¹,

Provost

Tchamitchian³

et al. 2016

Sci Rep

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“…Similar results of acaricide-induced cytotoxicity have been reported in cell lines derived from the insect Spodoptera frugiperda treated with permethrin [26] and in a Drosophila melanogaster embryo-derived cell line treated with fipronil [27]. It has been suggested that these in vitro toxic effects are due to oxidative stress and the subsequent activation of apoptosis [27–29].…”

Section: Discussionsupporting

confidence: 68%

“…It has been suggested that these in vitro toxic effects are due to oxidative stress and the subsequent activation of apoptosis [27–29]. …”

Section: Discussionmentioning

confidence: 99%

Exposure to amitraz, fipronil and permethrin affects cell viability and ABC transporter gene expression in an Ixodes ricinus cell line

et al. 2018

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BackgroundOver-expression of ATP-binding cassette (ABC) transporter proteins has been implicated in resistance of ticks to acaricides. Tick cell lines are useful for investigating resistance mechanisms, as development of an in vitro model for the study of acaricide resistance would contribute to improving knowledge of the molecular basis behind drug processing and exclusion in ticks. In the present study, cultures of the Ixodes ricinus-derived cell line IRE/CTVM19 were treated with the acaricides amitraz, permethrin or fipronil to determine modulation of ABC transporter gene expression. Cells were treated with different drug concentrations (25, 50, 100, 150 μM) and incubated for ten days. Cell morphology, viability, metabolic activity and relative expression of ABC (B1, B6, B8 and B10) genes were determined at day 10 post-treatment.ResultsCell morphology determined by light microscopy was altered following treatment with all drugs, but only at high concentrations, while total cell numbers decreased with increasing drug dose. Cell viability determined by trypan blue exclusion was not significantly different from untreated controls (P > 0.1) following treatment with amitraz and permethrin, but high concentrations of fipronil caused decrease (up to 37%, P < 0.01) in viability. At all drug concentrations, fipronil and permethrin induced dose-dependent reduction in cell metabolic activity measured by MTT assay (P < 0.01). Quantitative RT-PCR showed that the drugs significantly affected expression of ABC genes. In particular, fipronil treatment downregulated ABCB1 (P < 0.001) and upregulated ABCB6, ABCB8 and ABCB10 (P < 0.01); amitraz treatment down regulated ABCB1 (significant difference between 25 and 150 μM, P < 0.001) and upregulated ABCB8 and ABCB10 at lower concentrations (25 and 50 μM, P < 0.05); and permethrin upregulated ABCB6, ABCB8 and ABCB10 only at 150 μM (P < 0.01).ConclusionsThe adverse effects on cell viability and metabolic activity, and changes in expression of different ABC transporter genes, detected in IRE/CTVM19 cells following treatment with amitraz, permethrin and fipronil, support the proposed application of tick cell lines as in vitro models for the study of resistance to these acaricides in ticks.

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“…After the death receptor, located on the cell membrane, receives stimulation signals, the initial caspase is activated by the extrinsic pathway (extrinsic) and intrinsic pathway (mitochondrial pathway). Finally, the executed caspase is activated to make the relevant substrate degradation and induce apoptosis (Fuchs & Steller, 2011;Zhang et al, 2015). Among them, caspase-3 is the major effector protein of apoptosis that is activated by an initiator caspase as caspase-9.…”

Section: Discussionmentioning

confidence: 99%

“…Cell viability, as a testing endpoint of cytotoxicity, was determined by MTT assays (Zhang et al, 2015). This assay measures the conversion of MTT to purple formazan by succinate dehydrogenase of the intact mitochondria of living cells.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Potential threat of Chlorpyrifos to human liver cells via the caspase-dependent mitochondrial pathways

Zhang

Chang

Hong-ping

et al. 2017

Food and Agricultural Immunology

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Chlorpyrifos (CPF) has been widely used around the world as a pesticide for both agricultural and residential application. Although various studies have reported toxicity and health-related effects from CPF exposure, the potential threat and the molecular mechanism of CPF toxicity to human liver have not been wellcharacterized. In this study, we identify cytotoxicity of CPF to human normal liver cells in vitro. We demonstrate that the viability of QSG7701 cells is inhibited by CPF in a time-and concentration-dependent manner. Intracellular biochemical assays showed that CPF-induced apoptosis of QSG7701 cells concurrent with a decrease in the mitochondrial membrane potential, the release of cytochrome c into the cytosol, up-regulate the expression level of Bax/Bcl-2 and a marked activation of caspase-9/-3. These results indicate that CPF has a potential risk to human liver that can induce apoptosis of human liver cells through caspase-dependent mitochondrial pathways. ARTICLE HISTORY

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Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells

Cited by 47 publications

References 60 publications

Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential

Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential

Exposure to amitraz, fipronil and permethrin affects cell viability and ABC transporter gene expression in an Ixodes ricinus cell line

Potential threat of Chlorpyrifos to human liver cells via the caspase-dependent mitochondrial pathways

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