Toxicological evaluation of ametryn effects in Wistar rats

São Paulo state, Brazil, is one of the main areas of sugar cane planting in the world. Extensive use of ametryn, a triazine herbicide, in sugar cane agriculture and the properties of this herbicide suggest it could be present in the environment as a potential contaminant of soil, surface water, groundwater, and river sediment. In order to clarify the mechanism through which ametryn could be toxic, an in vivo study with Wistar rats was conducted using hematological, biochemical, molecular, morphological and genotoxic approaches. For this purpose, two sub-lethal ametryn concentrations (15 mg and 30 mg/kg/day) were administered to 42 rats divided into three groups (n=12) by gavage during 56 days, whereupon blood, liver and bone marrow were collected. The results showed ametryn genotoxic activity by in vivo micronuclei testing. This event probably occurred as consequence of oxidative stress induction demonstrated by GSTM1 transcript levels increase (indicating complexation between ametryn and/or metabolites with GSH) and by SOD activity decrease. Also, Mn-SOD transcripts were increased, probably avoiding mtDNA damage caused by EROS. These mechanisms displayed hepatic stellate cell (HSCs) activation because two major biomarkers were regulated, connexin and cadherin. N-cad transcripts were increased on both exposed groups while E-cad decreased in the T1 group, indicating epithelial-to-mesenchymal transition. In addition, Cx43 transcripts were decreased suggesting an increase in collagen content. Volumetric proportion of sinusoids was significantly decreased in T1 group and no significant alteration in hepatocyte volume was observed, indicating an increase in the space of Disse, due to fibrosis. Hepatocyte nuclei showed significant decrease in diameter and volume. Few hematological alterations were found. We emphasize the importance of other approaches, such as cell death and proliferation assays, so that ametryn toxicity can better be understood.