Avaliação in vitro do efeito dos pesticidas dimetomorfe e fenpropimorfe em células hepáticas humanas

Abstract

Brazil is one of the largest consumers of pesticides worldwide, and some of these compounds have had their use restricted by international regulatory agences due to the lack of knowledge regarding their impacts on human health. Among the most widely used classes, fungicides receive considerable attention given their high toxicological potential. Therefore, the present study aims to evaluate, in silico and in vitro, the effects of the morpholine fungicides dimethomorph (DIM) and fenpropimorph (FEN) on two human hepatic cell lines. The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions indicated a high hepatotoxic potential and a tendency toward bioaccumulation for both compounds. Cell viability was assessed using Sulforhodamine B assay after incubation of the cells at concentrations of 300, 150, 75, 37.5, 18.75, and 9.375 µg/mL for DIM and 2, 1, 0.5, 0.25, 0.125, and 0.0625 µg/mL for FEN over a 24-hour period. For the LX-2 cell line, only the concentrations of 300 µg/mL (DIM) and 1 µg/mL (FEN) showed a significant decrease in viability. In HepG2 cells, treatments below 75 µg/mL (DIM) and above 0.25 µg/mL (FEN) resulted in reduced viability and increased production of reactive oxygen species (ROS), highlighting the possible role of such molecules in hepatotoxicity mechanisms and cell death. Additional studies are required to elucidate the molecular mechanisms involved.