Abstract
This study examined if quercetin (QUR) prevents cadmium chloride (CdCl2)-induced hippocampal neurotoxicity in male rats by activating sirtuin-1 (SIRT1). Rats were divided into control, control + QUR, CdCl2, CdCl2 + QUR, and CdCl2 + QUR + EX-527 (a SIRT1 inhibitor). QUR (25 mg/kg) and CdCl2 (0.5 mg/kg) were administered orally for 30 days. QUR improved the structure of the dental gyrus and the spatial and avoidance memories of CdCl2-treated rats. Besides, QUR inhibited oxidative stress, inflammation, and apoptosis, increased glutathione (GSH) and manganese superoxide dismutase (MnSOD), acetylcholine (Ach), and brain-derived neurotrophic factor (BDNF) levels but downregulated acetylcholine esterase (AchE) in the hippocampi of rats. These effects were associated with higher hippocampal expression and activities of SIRT1 and decreased acetylation of Nrf2, NF-kappa B p65, and p53. Except for Ach and AChE, all these effects were prevented by EX-527. In conclusion, QUR prevents CdCl2 hippocampal neurotoxicity by activating SIRT1 and inhibiting AchE.