Risperidone-induced bioenergetic disruption in the isolated human peripheral blood monocytes.

Autor: Alenazi B; Pharmacology Department, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia., Al Doghaither HA; Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Al-Ghafari AB; Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Elmorsy EM; Pathology Department, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia. Electronic address: Ekramy.elmorsy@nbu.edu.sa.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2024 Dec; Vol. 101, pp. 105936. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.tiv.2024.105936
Abstrakt: Risperidone (RIS) is a widely used antipsychotic drug with reported alteration in immune response. The current study investigated mitochondrial disruption as the underlying mechanism of RIS-induced immunotoxicity in isolated human peripheral blood monocytes (hPBM). RIS was cytotoxic to hPBM in exposure duration and concentration-dependent patterns. Functionally, RIS was shown to increase the release of IL-6, TNF-α, and IL-8 with a decrease in test particle phagocytosis in concertation and exposure time-based patterns. It was found that RIS decreased ATP production in isolated monocytes' mitochondria, with an estimated EC50 of around 70 μM after 24 h with parallel inhibition of mitochondrial complexes I and III activities and decreased mitochondrial membrane potential and oxygen consumption rates with increased lactate production from by the treated cells in comparison to controls. Structurally, RIS in 100 μM concentration significantly increased the mitochondrial membrane fluidity with significant increase in increased unsaturated/saturated fatty acids ratios of the mitochondrial membranes of the treated cells. Interestingly, water-soluble CoQ10 formulation significantly decreased the cytotoxic effect of RIS and improved the phagocytic activity of RIS-treated cells. To conclude, the current data suggests mitochondrial disruption as the underlying mechanism of RIS-induced immunotoxicity with shown protective effect of water-soluble CoQ10 formulation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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