Coenzyme Q10 exhibits anti-inflammatory and immune-modulatory thereby decelerating the occurrence of experimental cerebral malaria.

Autor: Nyariki JN; Department of Biochemistry and Biotechnology, Technical of University of Kenya, P.O Box 52428-00200 Nairobi, Kenya. Electronic address: nyabukaj@tukenya.ac.ke., Kimani NM; Department of Physical Sciences, University of Embu, P.O Box 6-60100 Embu, Kenya., Kibet PS; Department of Pathology, Hematology and Blood Transfusion thematic unit, University of Nairobi, PO Box 30197-00100, Nairobi, Kenya., Kinuthia GK; Department of Science & Public Health, Daystar University, PO Box 44400-00100, Nairobi, Kenya., Isaac AO; Department of Pharmaceutical Sciences and Technology, School Health Sciences and Biomedical Sciences, Technical University of Kenya, P.O Box 52428-00200 Nairobi, Kenya.
Jazyk: angličtina
Zdroj: Molecular and biochemical parasitology [Mol Biochem Parasitol] 2023 Sep; Vol. 255, pp. 111579. Date of Electronic Publication: 2023 Jun 27.
DOI: 10.1016/j.molbiopara.2023.111579
Abstrakt: Cerebral Malaria (CM) is associated with the complex neurological syndrome, whose pathology is mediated by severe inflammatory processes following infection with Plasmodium falciparum. Coenzyme-Q 10 (Co-Q 10 ) is a potent anti-inflammatory, anti-oxidant, and anti-apoptotic agent with numerous clinical applications. The aim of this study was to elucidate the role of oral administration of Co-Q 10 on the initiation or regulation of inflammatory immune response during experimental cerebral malaria (ECM). For this purpose, the pre-clinical effect of Co-Q 10 was evaluated in C57BL/6 J mice infected with Plasmodium berghei ANKA (PbA). Treatment with Co-Q 10 resulted in the reduction of infiltrating parasite load, greatly improved the survival rate of PbA-infected mice that occurred independent of parasitaemia and prevented PbA-induced disruption of the blood-brain barrier (BBB) integrity. Exposure to Co-Q 10 resulted in the reduction of infiltration of effector CD8 + T cells in the brain and secretion of cytolytic Granzyme B molecules. Notably, Co-Q 10 -treated mice had reduced levels of CD8 +T cell chemokines CXCR3, CCR2, and CCR5 in the brain following PbA-infection. Brain tissue analysis showed a reduction in the levels of inflammatory mediators TNF- α, CCL3, and RANTES in Co-Q 10 administered mice. In addition, Co-Q 10 modulated the differentiation and maturation of both splenic and brain dendritic cells and cross-presentation (CD8α+DCs) during ECM. Remarkably, Co-Q 10 was very effective in decreasing levels of CD86, MHC-II, and CD40 in macrophages associated with ECM pathology. Exposure to Co-Q 10 resulted in increased expression levels of Arginase-1 and Ym1/chitinase 3-like 3, which is linked to ECM protection. Furthermore, Co-Q 10 supplementation prevented PbA-induced depletion of Arginase and CD206 mannose receptor levels. Co-Q 10 abrogated PbA-driven elevation in pro-inflammatory cytokines IL-1β, IL-18, and IL-6 levels. In conclusion, the oral supplementation with Co-Q 10 decelerates the occurrence of ECM by preventing lethal inflammatory immune responses and dampening genes associated with inflammation and immune-pathology during ECM, and offers an inimitable opening for developing an anti-inflammatory agent against cerebral malaria.
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 © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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