Effects of pesticide chemicals on the activity of metabolic enzymes: focus on thiocarbamates.

Cécile Mathieu, Romain Duval, Ximing Xu, Fernando Rodrigues-Lima, Jean-Marie Dupret

Expert opinion on drug metabolism & toxicology 2015 Jan

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Thiocarbamates are chemicals widely used as pesticides. Occupational exposure is associated with acute intoxication. Populations can be exposed through food and water. Moreover, certain thiocarbamates are used clinically. The widespread use of thiocarbamates raises many issues regarding their toxicological and pharmacological impact. Thiocarbamates and their metabolites can modify biological macromolecules functions, in particular enzymes, through modification of cysteine residues, chelation of metal ions or modulation of the oxidative stress. Loss of enzyme activity can lead to the disruption of metabolic pathways, and explain, at least in part, the effects of these pesticides. Additionally, their reactivity and ability to easily cross biological barrier confer them a great interest for development of clinical applications. Many advances in the study of thiocarbamates metabolism and reactivity have led to a better knowledge of biological effects of these compounds. However, more data are needed on the determination of targets and specificity. Only few data concerning the exposure to a cocktail of pesticides/chemicals are available, raising the need to evaluate the toxic side effects of representative pesticides mixtures. Moreover, the dithiocarbamate Disulfiram has shown great potential in therapeutic applications and leads to the development of pharmacological thiocarbamates derivatives, highly specific to their target and easily distributed.

Citation

Cécile Mathieu, Romain Duval, Ximing Xu, Fernando Rodrigues-Lima, Jean-Marie Dupret. Effects of pesticide chemicals on the activity of metabolic enzymes: focus on thiocarbamates. Expert opinion on drug metabolism & toxicology. 2015 Jan;11(1):81-94