Neurotoxicidade associada à exposição crônica via inalatória e via oral ao ácido diclorofenóxiacético (2,4-D) em ratos

Abstract

Herbicides are agents made up of a wide variety of chemical or biological compounds designed to eliminate, fight, repel or control insects. Ingestion, respiration, or dermal contact with pesticides of the phenoxyacetic acid class, such as dichlorophenoxyacetic acid (2,4-D), can cause loss of appetite, nausea, vomiting, muscle fasciculation, and even cancer. 2,4-D-associated neurotoxicity is controversial. The aim of this study was to evaluate the possible neurotoxic effect of chronic oral and inhalation exposure of the herbicide dichlorophenoxyacetic acid (2,4-D). For the experiments, 80 male adult rats (200-250g) were divided into eight groups (n = 10): Group 1: nebulization with sodium chloride solution (NaCl); Group 2: food nebulized with sodium chloride solution (NaCl); Group 3: herbicide nebulization with 3.71 x 10-3 grams of active ingredient per hectare (g.i.a / ha); Group 4: nebulized feed with herbicide at a concentration of 3.71 x 10-3 g.i.a / ha; Group 5: 6.19 x 10-3 g.i.a / ha herbicide nebulization; Group 6: herbicide nebulized feed at a concentration of 6.19 x 10-3 g.i.a / ha; Group 7: 9.28 x 10-3 g.i.a / ha herbicide nebulization; Group 8: Nebulized herbicide feed at a concentration of 9.28 x 10-3 g.i.a / ha. Daily nebulization for 15 minutes for 6 months. For behavioral evaluation the behavioral tests were: Open Field Test and High Cross Maze, whose objective will be the observation of the general health, neurological reflexes, sensory skills and motor function of the animals used. Brain was collected for histological and immunohistochemical analysis. Results: The administration of 2,4-D for six months led to a deficit in the neurobehavioral tests that evaluated locomotion and anxiety level of animals, regardless of the exposure route (oral or inhaled). There was individual necrosis of neurons and a decrease in the thickness of the cerebral cortex associated with increased expression of the BAX antibody (a pro-apoptotic marker). Conclusion: This study demonstrated that 2,4-D leads to neurodegeneration of the central nervous system by deregulation of pro-apoptotic proteins.