Efeitos do extrato da Alpinia zerumbet sobre a neurotoxicidade e as alterações comportamentais induzidas pelo 3, 3’, 4, 4’, 5-pentaclorobifenil (PCB 126)

Abstract

Polychlorinated biphenyls (PCBs) are synthetic compounds that have bioaccumulated and consequently contaminated the global ecosystem. Research has demonstrated the brain’s susceptibility to these compounds. In contrast, polyphenols have shown neuroprotective effects. Our research group has previously demonstrated that the extract from fresh leaves of Alpinia zerumbet (AZE), rich in polyphenols, exhibits antioxidant properties in a hypertension model. This study aimed to evaluate whether AZE can prevent neurotoxicity and behavioral changes induced by PCB126 in adult C57BL/6 mice. Male C57BL/6 mice were divided into four groups: Control, Control+AZE (50 mg/kg/day in drinking water), PCB (2 mg/kg/week), and PCB+AZE (2 mg/kg/week; 50 mg/kg/day). The treatments were administered over four weeks. At the end of the experiment, the animals underwent behavioral tests and were subsequently euthanized (CEUA/021/2021). We assessed oxidative stress and antioxidant activity in the brain stem, cerebellum, midbrain and left cortex, as well as markers of neurodegeneration and neuroinflammation through qPCR and Western Blotting in the right cortex. Differences between groups were analyzed using analysis of variance (ANOVA), followed by Tukey's post-hoc test, with significance considered when p<0.05. Our findings revealed a reduction in locomotor activity in the PCB group compared to controls, an effect mitigated by AZE treatment in the Elevated Plus Maze and Open Field Test. Notably, no anxious behavior was observed in these tests. AZE treatment also improved spatial memory in the PCB-exposed group, as demonstrated by the Object Location Test. There were no significant differences between groups in the Forced Swim Test. The PCB group showed increased lipid peroxidation in the brainstem and left cortex relative to the Control+AZE group, an increase that was prevented by AZE treatment in the PCB+AZE group. AZE treatment was associated with significantly higher activity of the antioxidant enzyme Catalase in the cerebellum and midbrain. Although there were no statistical differences in dopamine levels in the cortex of both hemispheres, levels of serotonin, glutamate, GABA and acetylcholine were elevated in the groups exposed to PCB and treated with AZE. In the right cortex, there were no differences in Parp-1, Bcl-2, and M1 receptor levels, but an increase in the pro-apoptotic protein Bax was observed in the PCB group, which was prevented by AZE treatment. In the hippocampus, the PCB-exposed group showed a reduction in the anti-apoptotic protein Bcl-2. Additionally, there was an increase in tyrosine hydroxylase expression in the PCB+AZE group and a decrease in D2 receptor expression in the PCB group. No significant statistical differences were found in the expression of Bax, M1 receptor, and BDNF in the hippocampus. There were no differences in RNAm expression of neuroinflammation markers in the right cortex. In conclusion, the results indicate that the extract of Alpinia zerumbet effectively prevents the development of locomotor deficits induced by PCB, does not induce anxious behavior and improves spatial memory. Moreover, the extract prevents oxidative damage and a reduction in antioxidant activity across different brain regions and beneficially prevents alterations in apoptosis-associated proteins, suggesting a neuroprotective effect.