RESUMO
Brazil is a global agricultural commodity producer and the largest consumer of pesticides. Intern pesticide use comprised 549,280 thousand tons in 2018. In the country, soybean, corn, and sugar cane are extensively produced, which are the most pesticides demanding crops. In the last years, the records of new pesticides were the highest in the historical series. They can persist in soil or water, accumulate in organisms, and contaminate workers and the general population through the air, water, or food. This review aimed to gather toxicological data obtained by animal models exposed to four pesticides: glyphosate, chlorpyrifos, abamectin, and 2,4‐D. Besides, to compose an overview of how this subject has been approached, surveying which research groups are working on this field, where they are located and relations with pesticides used in those regions. We collected the papers from the platforms PubMed, Scopus, Scielo, and Web of Science, performed in Brazil from 2014 to 2019. After two‐step blind selection using the software Rayyan QCRI by different authors, 67 studies were selected to extract data. We observed that research is more concentrated in the South region, followed by the Southeast and Midwest, with 43, 32, and 23% of the studies, respectively. The prevalent institutions are from the states of Rio Grande do Sul, São Paulo, and Goiás. The effects on a variety of biomarkers help predict the potential risks in humans and non‐target organisms. The prevalent animal model was fish (36%). Overall, the main toxic effects evaluated were mortality, abnormalities in the blood cells, developmental abnormalities, and behavior alterations.
RESUMO
N-(2-butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (NBCN) is a nitroaromatic bioreducible compound with cytotoxic effects in cancer cell lines. The aim of this work was to investigate the molecular mechanisms involved in cell death promoted by NBCN in HL60 cells. We observed that NBCN treatment increased intracellular ROS and reduced mitochondria membrane potential (ΔΨm). NBCN treatment also induced morphological changes, phosphatidylserine exposure, cell cycle arrest in G2/M-phase, DNA condensation and fragmentation, but it did not show cytotoxic effects on normal human peripheral blood mononuclear cells (PBMCs). NBCN-induced caspase 3- and 9-dependent DNA fragmentation, which was blocked by pretreatment with the broad-spectrum caspase inhibitor, z-VAD-fmk. Flow cytometry analysis demonstrated that NBCN also increased of the number of autophagic vesicles in HL60 cells, which was not observed when cells were pre-treated with bafilomycin A1. Taken together, these results indicate that NBCN triggered the mitochondrial apoptotic pathway and led to the onset of autophagic cell death, which contributed to its cytotoxic effects.
