Co-administration of chloroquine and co-enzyme Q10 reduces neurological deficits, brain edema, and breach of the blood-brain barrier in experimental cerebral malaria

Cerebral malaria is characterized by severe neurological deficits, lethal inflammation and oxidative stress. The current study sought to establish if co-administration of co-enzyme Q10 (CoQ10), a potent antioxidant, anti-inflammatory and chloroquine (CQ) can improve treatment outcome in an experimental cerebral malaria (ECM). Mice were divided into five groups: control, PbA-infected, and PbA-infected treated with CoQ10, CoQ10 plus chloroquine, or chloroquine alone, using doses of 200 mg/kg for CoQ10 and 50 mg/kg for chloroquine. The study evaluated relative organ weights, neurological symptoms, blood-brain barrier integrity (BBB), hematological profile, creatinine, urea uric acid, albumin, nitrite levels, lipid peroxidation and brain pathology. Rapid murine coma and behavioral scale (RMCBS) data showed that combined CQ and CoQ10 treatment significantly improved neurological symptoms linked to ECM. This therapeutic regimen also prevented the disruption of the blood-brain barrier (BBB) during severe Plasmodium berghei ANKA (PbA) infection. Notably, it attenuated PbA-induced brain edema, leukopenia, microcytic hypochromic anemia, and thrombocytopenia, and restored the PbA-associated reduction trend in lung relative organ weight. The CQ/CoQ10 combination abrogated PbA-driven elevations in creatinine, urea, and uric acid, and was most effective in restoring depleted albumin and nitric oxide (NO) levels. Additionally, it reduced PbA-induced malondialdehyde (MDA) levels. Signs of brain injury, such as focal gliosis and perivascular cuffing, were also ameliorated. In conclusion, this regimen enhanced therapeutic efficacy, evidenced by improved RMCBS scores, preserved BBB integrity, and correction of hematological and biochemical abnormalities. CoQ10, used alongside CQ, shows promise as adjunct therapy, supporting evaluation in additional preclinical studies.