Alterações comportamentais e fisiológicas após exposição crônica de cletodim em ratos

Abstract

Clethodim (CL) is a selective herbicide belonging to the oxime-cyclohexanedione chemical group, whose mechanism of action involves the inhibition of acetyl coenzyme A. It is widely used to combat plants that are resistant to glyphosate. Due to the scarcity of studies in the literature on the impacts of this compound on human or animal health, studies seeking to assess its toxicity in non-target organisms are necessary. The objective of this study was to evaluate behavioral and physiological changes after repeated exposure to CL in rats. As materials and methods, after obtaining approval from the Animal Use Ethics Committee of the Federal University of Sergipe (CEUA/UFS) under protocol no. 5228100323, 30 adult male rats aged 6- 8 months (350-500 g) of the Wistar strain were used. The animals were divided into four groups with seven to eight animals per group, according to the concentration of the compound: control (CTL-0.9% saline solution), CL at concentrations of 0.06% (CL-0.06), 0.3% (CL-0.3), and 0.6% (CL-0.6). Twenty-five nebulization exposures were performed (one every 48 hours, lasting 10 minutes each) with saline solution or CL according to the experimental group. Throughout the experiment, behavioral tests were performed, namely: catalepsy (every 48 hours), open field (OF - days 0 and 38), novel object recognition (NOR - day 12), spontaneous alternation (SA - day 16), and forced swim test (FST - day 25). In addition, assessments of body mass (every 4 days), food intake (day 44), glycemic tolerance (day 48), and organ mass measurement and brain removal after perfusion (day 50) were performed. The brains were then processed to assess the immunoreactivity of Brain-Derived Neurotrophic Factor (BDNF), cFos, and Choline-O-Acetyl-Transferase (ChAT) proteins. Our results showed that the CL-0.06 group had a shorter time in the catalepsy test and lower spleen mass; in the CL-0.6 group, we observed a shorter time in the center in the CA and impairment in working memory in the AE, but not in the RO, increased body variation, and lower glycemic peak in the glucose tolerance test; in all concentrations, we observed lower food consumption and a higher number of immobility events with longer immobility time in the TNF. Regarding neurochemical assessments, lower immunoreactivity for BDNF and c-Fos was identified in hippocampal regions in the CL-0.06 and CL-0.3 groups, with no changes in ChAT expression in cholinergic areas. In conclusion, our study demonstrated that exposure to CL according to concentration was capable of promoting anxiety- and depression-like behavior, memory deficits, increased body mass, and decreased hippocampal activity.