%0 Journal Article
%T Quetiapine attenuates cadmium neurotoxicity by suppressing oxidative stress, inflammation, and pyroptosis.
%A Althagafy HS
%A Harakeh S
%A Azhari SA
%A Farsi RM
%A Al-Abbas NS
%A Shaer NA
%A Sharawi ZW
%A Almohaimeed HM
%A Hassanein EHM
%J Mol Biol Rep
%V 51
%N 1
%D 2024 May 15
%M 38750264
%F 2.742
%R 10.1007/s11033-024-09558-7
%X <B>BACKGROUND: </B>Cadmium (Cd) is a heavy metal with extremely harmful toxic effects on the brain. Quetiapine (QTP) has unique neuroprotective effects with anti-inflammatory and antioxidant actions. However, its neuroprotective effect against Cd-induced neurotoxicity has not been previously studied.<BR><B>METHODS: </B>QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg.<BR><B>RESULTS: </B>In our study, QTP dose-dependently attenuated neuronal injury by downregulating p-tau and β-amyloid. QTP potently attenuates histological abrasions induced by Cd. QTP counteracted oxidative injury by decreasing neuronal MDA and increased GSH levels mediated by downregulating Keap1 and upregulating Nrf2 and HO-1. QTP mitigated inflammation by decreasing MPO and NO2 and neuronal cytokines TNF-α and IL-1β and upregulating IL-10 levels mediated by NF-κB downregulation. Additionally, QTP counteracted Cd-induced pyroptosis by downregulating caspase-1, ASC, and NLRP3 protein levels.<BR><B>CONCLUSIONS: </B>In conclusion, QTP mitigates neurotoxicity induced by Cd through suppression of inflammation, pyroptosis, and oxidative stress by controlling the NF-κB, Keap1/Nrf2, and pyroptosis signals.