Bifenthrin causes disturbance in mitochondrial dynamics and bioenergetic system in human embryonic kidney cells (HEK...

Synthetic pyrethroids (SPs) such as bifenthrin (BF) have been used worldwide in pest control due to their high insecticidal activity and low toxicity to mammals. However, due to their lipophilicity, BF can persist in various environments and cause significant adverse effects on non-target organisms, including humans. Mitochondria, crucial for cellular energy production and homeostasis, are primary targets of environmental toxins like BF. This study, which investigated the impact of BF on mitochondrial function in human embryonic kidney (Hek 293) cells, found that BF caused cytotoxicity via a reduction in cell viability assessed by the MTT assay and triggered apoptosis in cells characterized by nuclear condensation and formation of apoptotic bodies revealed through the AO/PI study. BF exposure also led to a marked increase in reactive oxygen species (ROS) levels and a significant reduction in mitochondrial membrane potential (MMP), indicating oxidative stress and mitochondrial dysfunction. BF treatment concentration of 1.00 μM and 2.00 μM significantly affects mitochondrial respiratory capacity by lowering the basal and maximal respiration, ATP production, and spare respiratory capacity, leading to mitochondrial impairment. Gene expression analysis also showed BF exposure altered the expression of genes related to mitochondrial fusion (MFN1, MFN2, OPA1) and fission (FIS1, DRP1), suggesting a disruption in the balance of mitochondrial dynamics. Defects in mitochondrial dynamics caused fragmentation of the mitochondrial branch length and number in BF induced cell compared to control. The analysis of mRNA expression of apoptosis genes also indicated that BF induced cell death. This study demonstrated that BF induced cytotoxicity disrupted mitochondrial membrane potential and impaired mitochondrial bioenergetics. Therefore, this finding emphasizes the significance of understanding the impact of BF on mitochondrial function, highlighting the need for further research and action to mitigate the potential long-term human health risks associated with this pesticide.