EFEITOS METABÓLICOS E TOXICIDADE DOS PESTICIDAS ATRAZINA E GLIFOSATO IN VIVO E IN VITRO

Abstract

The increased use of pesticides in Brazil and worldwide has raised concerns among society and the scientific community regarding the risks these substances pose to the environment and human health. Among the most widely used pesticides are the herbicides atrazine and glyphosate. Both can act as endocrine disruptors and cause undesirable metabolic changes. This study aimed to evaluate, in an animal model, the metabolic effects of exposure to commercial pesticide formulations during critical developmental windows, as well as to assess whether there are differences between the commercial formulation and the isolated active ingredient in inducing oxidative stress and gene expression in a human hepatocyte cell line. Results from an initial study showed that maternal exposure during gestation and lactation to the glyphosate- based herbicide (GBH) promoted a reduction in body weight gain and retroperitoneal and perigonadal fat stores in the adult offspring of male mice fed a high -fat diet (HFD). In addition, greater glucose tolerance and insulin sensitivity were observed, as well as a lower degree of hepatic steatosis. In another study, it was observed that male and female mice exposed in the peripubertal period to the atrazine-based herbicide (ABH) at a dose of 5 mg/kg body weight and then fed an HFD for 90 days, showed differentiated responses to the herbicide. Although body weight and adiposity remained unchanged, male mice exposed to ABH showed hypertrophy of adipocytes and upregulation of genes involved in fatty acid uptake and lipid droplet regulation in perigonadal adipose tissue. Furthermore, pubertal exposure to ABH exacerbated hepatic steatosis in both sexes, with increased ectopic fat accumulation in females, correlating with increased expression of genes encoding proteins involved in fatty acid uptake and export. In a third study, the differential toxicity between the active ingredient glyphosate and GBH was evaluated in HepG2 cells. Exposure to GBH resulted in increased production of hydrogen peroxide in the mitochondria, and RNA sequencing data showed 7371 differentially expressed genes compared to isolated glyphosate, highlighting pathways related to oxidative stress, endoplasmic reticulum stress, autophagy and apoptosis. The joint analysis of the results demonstrates that GBH and ABH have the potential to act as endocrine disruptors and obesogens, respectively. The observed effects vary according to the exposure period and sex of the animals, evidencing the complex toxicity of these compounds. GBH proved to be even more toxic than the isolated active ingredient in hepatocytes. These results reinforce the need for stricter regulations for pesticides, emphasizing the importance of studies that assess long-term effects, as well as the toxicity of all ingredients present in commercial formulations.