Neurotoxicity associated with chronic exposure to dichlorophenoxyacetic acid (2,4-D) – a simulation of environmental exposure in adult rats

Abstract

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is the second most widely used herbicide in the world. The objective of this study was to evaluate the neurotoxic effects and the possible role of the dysregulation of apoptosis in the genesis of brain damage in chronic exposure to 2,4-D in rats. Eighty adult male rats were distributed into eight groups (n = 10) and exposed orally (contaminated feed) and via inhalation, with two groups exposed to distilled water (control) and six to 2,4-D in three distinct concentrations. They were exposed for 6 months. A neurobehavioral assessment was performed, and the brain was collected for histopathology and immunohistochemistry. The animals in the control groups showed greater motility in the open-field test and a greater number of entries in the elevated-plus-maze test than those exposed to 2,4-D (p < 0.05). Neuronal necrosis was more incident in animals exposed to 2,4-D (p < 0.05). There was a negative correlation between the expression of BAX and the measurement of the cerebral cortex thickness (r = −0.713; p = 0.047). Regardless of the route of exposure, 2,4-D led to a deficit in neurobehavioral tests and decreased thickness of the cerebral cortex associated with increased expression of the pro-apoptotic protein BAX.

Keywords:

• Central nervous system
• cell cycle
• pesticides
• behavior
• environment

Acknowledgments

The authors would like to thank the technicians of the Laboratory of Surgical Pathology and Cytopathology of UNOESTE, Carlos Alexandre Santana de Oliveira, Mariana Fonseca Motta Borges and Talita Rizo Pereira, for the histological processing of the specimens, and Professor Rui Daniel Schroder Prediger of the Department of Pharmacology at the Federal University of Santa Catarina (Florianópolis, SC, Brazil) for the guidelines for the performance of behavioral tests. V. M. Souza received a scholarship from the Scientific Initiation Scholarship Program of the National Council for Scientific and Technological Development (PIBIC/CNPq).

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This work was funded by research funds from the Universidade do Oeste Paulista (UNOESTE).