Abstract
African trypanosomiasis remains a lethal disease to both humans and livestock. The disease persists due to limited drug availability, toxicity and drug resistance, hence the need for a better understanding of the parasite’s biology and provision of alternative forms of therapy. In this study, the in vitro effects of phenolic acids were assessed for their trypanocidal activities against Trypanosoma brucei brucei. The effect of the phenolic acids on Trypanosoma brucei brucei was determined by the alamarBlue assay. The cell cycle effects were determined by flow cytometry and parasite morphological analysis was done by microscopy. Effect on cell proliferation was determined by growth kinetic analysis. Reverse Transcriptase quantitative Polymerase Chain Reaction was used to determine expression of iron dependent enzymes and iron distribution determined by atomic absorption spectroscopy. Gallic acid gave an IC50 of 14.2±1.5 μM. Deferoxamine, gallic acid and diminazene aceturate showed a dose dependent effect on the cell viability and the mitochondrion membrane integrity. Gallic acid, deferoxamine and diminazene aceturate caused loss of kinetoplast in 22%, 26% and 82% of trypanosomes respectively and less than 10% increase in the number of trypanosomes in S phase was observed. Gallic acid caused a 0.6 fold decrease, 50 fold increase and 7 fold increase in the expression levels of the transferrin receptor, ribonucleotide reductase and cyclin 2 genes respectively while treatment with deferoxamine and diminazene aceturate also showed differential expressions of the transferrin receptor, ribonucleotide reductase and cyclin 2 genes.The data suggests that gallic acid possibly exerts its effect on T. brucei via iron chelation leading to structural and morphological changes and arrest of the cell cycle. These together provide information on the cell biology of the parasite under iron starved conditions and provide leads into alternative therapeutic approaches in the treatment of African trypanosomiasis.
Highlights
African trypanosomiasis (AT) is an infectious disease that affects humans, domestic and wild animals in sub-Saharan Africa and it is transmitted by the tsetse fly [1]
In addition to the cell cycle analysis and measurement of the expression levels of the transferrin receptor, ribonucleotide reductase and the cyclin gene, we investigated the effect of the chelators on the parasites’ morphology and the mitochondrial membrane integrity
In vitro trypanocidal activity of compounds against Trypanosoma brucei To investigate the effects of the compounds on cell viability, trypanosome cells were incubated with varying concentrations of compounds for 72 hours
Summary
African trypanosomiasis (AT) is an infectious disease that affects humans, domestic and wild animals in sub-Saharan Africa and it is transmitted by the tsetse fly [1]. Anti-trypanosomal effects of phenolic acids on Trypanosoma brucei (T. brucei) is responsible for causing AT in both cattle and humans [2]. Trypanosoma brucei brucei is one of the causative agents of Animal African Trypanosomiasis (AAT) or nagana in cattle. About 55 million cattle are at risk with the disease leading to a loss of three million animals annually [4]. Due to the antigenic variation exhibited by the parasites, there is currently no vaccine against trypanosomes the mode of treatment is mainly by chemotherapy [5]. The urgent need for the development of new anti-trypanosomal therapeutics which are safe and efficacious
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