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Quetiapine attenuates cadmium neurotoxicity by suppressing oxidative stress, inflammation, and pyroptosis.

Authors :
Althagafy, Hanan S.
Harakeh, Steve
Azhari, Sheren A.
Farsi, Reem M.
Al-Abbas, Nouf S.
Shaer, Nehad A.
Sharawi, Zeina W.
Almohaimeed, Hailah M.
Hassanein, Emad H. M.
Source :
Molecular Biology Reports; 5/15/2024, Vol. 51 Issue 1, p1-16, 16p
Publication Year :
2024

Abstract

Background: 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. Methods: QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg. Results: 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 NO<subscript>2</subscript> 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03014851
Volume :
51
Issue :
1
Database :
Complementary Index
Journal :
Molecular Biology Reports
Publication Type :
Academic Journal
Accession number :
177250255
Full Text :
https://doi.org/10.1007/s11033-024-09558-7