Mielotoxicidade e hepatotoxicidade da exposição crônica ao herbicida a base de glifosato em camundongos C57BL/6

Abstract

Introduction: The use of glyphosate-based herbicides (GBH) has intensified over the past decades, accompanying the expansion of agricultural production. This scenario has raised concerns regarding the potential health effects of chronic exposure to these compounds. Experimental studies have demonstrated alterations in various biological systems following exposure to glyphosate and commercial formulations containing this herbicide, including hepatic and hematological effects. However, the effects of chronic exposure on the bone marrow and the mechanisms involved in hematotoxicity remain incompletely understood. Objective: To evaluate the effects of chronic exposure to 5 and 50 mg/kg doses of a commercial GBH formulation on hematological parameters, bone marrow, and liver of male C57BL/6 mice. Methods: Male C57BL/6 mice, approximately 21 days old and with a mean body weight of 20 g, were distributed into three experimental groups: control (CTL), 5 mg/kg GBH (GBH-5), and 50 mg/kg GBH (GBH-50). The mice received the commercial formulation Xeque Mate HT® diluted in drinking water ad libitum for 20 weeks. At the end of the experimental period, following euthanasia, body profile assessment, hepatic histopathological analysis, complete blood count and reticulocyte count, cytological and histological evaluation of the bone marrow, and serum thrombopoietin (TPO) measurement were performed. Results: GBH exposure increased water and food consumption, without significantly affecting final body weight gain. Hepatic histopathological evaluation revealed hepatocellular hypertrophy, inflammatory infiltrate, and increased connective tissue. Regarding hematological evaluation, no relevant alterations in erythropoiesis were observed; however, alterations in the leukocyte profile were identified, with more pronounced leukocytosis, neutrophilia, and monocytosis in both GBH-exposed groups. In addition, platelet counts were reduced in the GBH-5 and GBH-50 groups compared with the CTL group, by 26.39% and 46.45%, respectively. Bone marrow evaluation revealed a significant increase in megakaryocyte numbers in the GBH-50 group compared with the CTL and GBH-5 groups, along with dysplastic alterations consistent with impaired megakaryopoiesis. Serum TPO concentrations remained unchanged among the experimental groups. Conclusions: Chronic exposure to 5 and 50 mg/kg doses of a commercial GBH formulation promoted hepatic and hematological alterations, as well as changes in the bone marrow of C57BL/6 mice. The main findings were thrombocytopenia associated with dysmegakaryocytopoiesis, with no change in serum TPO concentrations. These findings suggest ineffective thrombopoiesis as one of the mechanisms involved in herbicide-induced hematotoxicity.