Abstract

RODRIGUES DA SILVA, Adielle  and  BISPO SOUSA, Sandra Mara. Succinate dehydrogenase inhibitors fungicides: a review of their impact on human health and epigenetic changes. Acta toxicol. argent. [online]. 2023, vol.31, n.1, pp.3-3. ISSN 1851-3743.

Succinate dehydrogenase inhibitors (SDHIs), fungicides currently most used in agriculture in Brazil, act by blocking the enzyme succinate dehydrogenase (SDH) from plant pathogens. However, studies show that SDHIs can not only inhibit SDH activity in target fungi, but also block that activity in human cells. Considering the medical and agricultural implications of SDH, the purpose of this narrative review is to describe the relationship between exposure to fungicides SDHIs and epigenetic regulation of SDH associated with the development of gastrointestinal stromal tumor, pheochromocytoma/paraganglioma, and cancer. The results obtained with the research showed that the human SDH enzyme exhibited sensitivity to some tested SDHIs, which may cause microcephaly and defects in neurological development. Deficiency of SDH activity causes accumulation of succinate which can act as an oncometabolite inhibit-ing iron-dependent dioxygenases and alpha-ketoglutarate, eleven translocation -TET and histone demethylases, inducing epigenetic changes that lead to multiple cancers and other diseases. Therefore, further in vitro and in vivo analyzes should be performed to assess susceptibility to diseases influenced by the toxic effect of SDHIs.

Keywords : SDHI; Agriculture; DNA methylation; Cancer; Paraganglioma; Gastrointestinal stromal tumor.

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