Assessing the Potential of Ginkgo Biloba in Ameliorating Melarsoprol-driven Toxicities and Improving Treatment Outcome in Human African Trypanosomiasis

Abstract

One of the under treated diseases, human African trypanosomiasis (HAT), necessitates novel therapeutic strategies, particularly in its severe late stage (CNS stage), that is marked by oxidative stress, severe brain inflammation, organ damage, and disruption of the blood-brain barrier. For severe Trypanosoma brucei rhodesiense (T.b.r) illness of the central nervous system, melarsoprol (MelB) is the sole available treatment. MelB's toxicity, primarily fatal brain damage from post-treatment reactive encephalopathy, limits its use. The current investigation assessed the ability of Ginkgo biloba (GB), a strong antiinflammatory and antioxidant, to preserve the blood-brain barrier's integrity and reduce harmful inflammation and free radical damage from Trypanosoma brucei rhodesiense in mice given melarsoprol. 6-8 weeks old, male Swiss white mice, 10 per experimental group, were employed in this investigation. Group one entailed the control; group two of mice had trypanosome infection; the third group had T.b.r infection and received melarsoprol 2.2 mg per kilogram for 10 days; the fourth group received oral GB 80 mg per kilogram up to 30 days after trypanosome infection; the fifth group received oral GB 80 milligrams per kilogram up to 14 days before infection and throughout the treatment period and the sixth group was inoculated with trypanosomes, given GB with intraperitoneal melarsoprol. The animals were infected and monitored for a period of up to 50 days. Parasitaemia was monitored daily from the second day post-infection. Determination of weekly rapid murine coma and behavioral scale scores (RMCBS), body as well as organ weights was done. Further analysis focused on elucidating the integrity of various biochemical and physiological systems within the experimental design. The Log-rank (Mantel-Cox) Test was utilized to

assess survival rate. When MelB and GB were given together, the onset of infection was delayed by 6 days and the rate of survival of infected mice significantly (p<0.0001) enhanced. A similar trend in parasitaemia levels was observed through all experimental groups. The adjunct therapy with GB protected the blood-brain barrier’s integrity and enhanced neurological performance in diseased mice. Additionally, MelB given together with GB averted microcytic hypochromic anemia, as well as platelet depletion caused by T.b.r. Moreover, MelB administration with GB attenuated the down-regulation of total white blood cells (WBCs) and dyslipidaemia caused by T.b.r. Notably, GB prevented liver injury and blocked T.b.r-driven electrolyte imbalance. Moreover, MelB given together with GB prevented an increase in uric acid, urea, bilirubin and total proteins, caused by T.b.r, and impeded albumin depletion prompted by T.b.r. Infection with T.b.r prompted up-regulation of TNF-α and IFN-γ in serum, that was annuled by co-administration of MelB and GB. GB prevented oxidative stress caused by MelB and T.b.r in the heart, brain, liver, kidney, spleen, and lungs; as well as lipid peroxidation. Notably, GB promoted reduction in peroxidation and oxidant harm by reducing T.b.r and MelB-caused increase in malondialdehyde (MDA) in the brain, liver, kidney and serum.GB lessened the up-regulation of nitric oxide (NO) caused by T.b.r and MelB. Histological examination showed that GB could offer some protection against organ degeneration. In conclusion, co-administration of MelB and GB could be helpful in remediating brain and organ injury, lethal inflammation, oxidative stress and anemia in T.b.r HAT disease. It is evident that GB ameliorates MelB toxicity, while protecting from T.b.r-driven pathological sequelae