Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

Abstract

Succinate dehydrogenase inhibitors (SDHIs) are the most widely used fungicides against plant parasitic fungi. They act by blocking the enzyme succinate dehydrogenase (SDH), a key component of mitochondrial respiration, which is highly conserved throughout evolution. Recently, it has been reported that some SDHIs used in many fungicides do not only inhibit the SDH activity of target fungi but can also block several non-target human cells in in vitro models. This study reveals a lack of SDHI species specificity and so points to a major health risk for exposed organisms, including humans. Despite the frequent detection of SDHIs in the environment and on harvested products and their increasing use in modern agriculture, their potential toxic effects in vivo, especially on neurodevelopment, are still under-evaluated. Here, we assessed the neurotoxicity of bixafen, one of the latest-generation SDHIs, which had never been tested during neurodevelopment. For this purpose, we used a well-known vertebrate model for toxicity testing, namely zebrafish transparent embryos, and live imaging using transgenic lines labelling the brain and spinal cord. Here we show that bixafen causes microcephaly and defects on motor neuron axon outgrowth and their branching during development. Our findings show that the central nervous system is highly sensitive to bixafen, thus demonstrating for the first time in vivo that an SDHI, bixafen, widely used in agriculture, is neurotoxic in vertebrates and causes neurodevelopmental defects. This work adds to our knowledge of the toxic effect of SDHIs on neurodevelopment and may help us take the appropriate precautions to ensure protection against the neurotoxic effects of these substances

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

“…Other recent reports revealed neurodevelopmental defects in zebrafish models after exposure of embryos to Bixafen or Boscalid a few hours post-fertilization [ 5 , 6 ] as well as severe cardiac toxicity [ 7 ]. Chronic exposures (28 days) of adult zebrafish led to alterations in carbohydrate and lipid metabolism, and induced damage in the kidneys and the liver [ 8 ].…”