THE ROLE OF COENZYME-QlO IN THE REGULATION OF ThTFLAMMATORY IMMUNE RESPONSES DURING EXPERIMENTAL CEREBRAL MALARIA IN MICE

Abstract

Cerebral Malaria (CM) is a form of malaria that causes a complex neurological syndrome, whose ~ology is mediated by severe inflammatory processes triggered by the immune system of the : 5t following infection with Plasmodium Jalciparum. There is limited progress in the -. development of new approaches for the treatment of CM. The aim of this study was to -~-:ematically elucidate the putative impact of oral administration of Coenzyme-QlO (CO-QIO) on ~ initiation or regulation of inflammatory immune response in experimental cerebral malaria \1). In addition, the ability of CO-Q lO to assuage ECM-induced inflammation and oxidative _ss was detennined. For this purpose, one group of C57BLl6J mice was used as control; the _::lnd group was infected with Plasmodium berghei ANKA (PbA) and the third group of mice -. orally supplemented with 200mglkg CO-Q IO and then infected with PbA. Within this -:--erimental set up, a series of experiments were carried out in concert with the study objectives. _... included: survival analysis, extensive clinical and biochemical analyses, flow cytometry, rime PCR for mRNA levels, immunoblot and immune-based assays. It was observed that __dministration of CO-QlO both before and after PbA infection protected majority of mice --J ECM. Importantly, CO-QIO supplementation significantly hampered infiltration of -lmatory monocytes, T cells and cytotoxic granzyme B into the brain. Brain tissue analysis ed a reduction in the expression levels of inflammatory transcripts TNF -u and MIP-l ~ in administered mice. Furthermore, CO-QlO administration resulted in decreased expression -~okines (CXCL9, CXCL 10) in the brain, leading to reduced levels of activated pathogenic _ -with concomitant improvement in blood brain barrier disruption. In addition, CO-QIO __ 91ed the differentiation and maturation of both splenic and brain dendritic cells during '\otably, anti-inflammatory cytokines IL-IO and IL-22 together with T-regulatory celis, -are associated with protection during ECM, were up-regulated in CO-QlO treated mice. -. ably, Co-QJO was very effective in decreasing NF-KB phosphorylation, which is _ -:-00 with ECM pathology. Splenic analysis of innate lymphoid class two (ILC2), which -.ll to playa protective role during ECM, showed augmentation in the spleens of CO-QIO . . ered mice. Meanwhile, levels of matrix metalloproteinases-9 and angiopoietin-l&2, :!..."'e linked to severity of CM were reduced in mice administered with CO-QIO. '----~~. . e. CO-Q IO supplementation abrogated malondialdehyde, diene and 8-hydroxy:'::::::trr:--2 osine \8-0HDG( which are markers of oxidative stress and DNA damall>e. Moreover,