Eucalyptol Attenuates Lead-Induced Anxiety-like Behaviors by Suppressing Oxidative Stress and Neuroinflammation, Modulating SIRT1/NF-κB Signaling, and Upregulating BDNF Expression.

Lead is an environmental pollutant that possesses harmful effects on the nervous system. The current study was conducted to investigate the impacts of eucalyptol, a type of monoterpene, on anxiety behaviors, oxidative stress, neuroinflammation, and neuronal death in the hippocampus of rats exposed to lead and its possible protective mechanism. Adult male Wistar rats were divided into Control, Lead, Eucalyptol, and Lead + Eucalyptol groups. The Lead and Lead + Eucalyptol groups were given lead acetate (25 mg/kg, gavage) daily for fourteen days. The Eucalyptol and Lead + Eucalyptol groups also received eucalyptol (100 mg/kg, gavage). The results showed that eucalyptol prevented an increase in malondialdehyde levels and a decrease in glutathione levels, as well as a reduction in the activity of superoxide dismutase and glutathione peroxidase enzymes in the hippocampus of Lead + Eucalyptol animals. It also prevented an increase in the expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)- 1β, and IL- 6, and a decrease in the expression of anti-inflammatory cytokine IL- 10. In addition, this monoterpene prevented the reduction in sirtuin 1 (SIRT1) expression and the increase in nuclear factor kappa b (NF-κB) expression. It enhanced the expression of brain-derived neurotrophic factor (BDNF) at the level of mRNA and protein and reduced neuronal death in different subfields of the hippocampus. Eucalyptol also improved the performance of rats receiving lead acetate in elevated plus maze and open field tests. We concluded that eucalyptol reduces anxiety behaviors in lead-exposed rats by suppressing oxidative stress, neuroinflammation, and neuronal death in the hippocampus. The anxiolytic effect of eucalyptol in lead pollution is likely mediated by modulating SIRT1/NF-κB signaling and increasing BDNF expression.