ABSTRACT
African trypanosomiasis still remains a lethal disease to both human and livestock. The disease persists due to limited drug availability, toxicity and emergence of drug resistance, hence the need to provide alternative forms of therapy. Studies have shown that the iron chelator deferoxamine exhibited anti-trypanosomal effects by inhibiting cell growth and interfering with the activity of some iron dependent enzymes. In this study, the in vitro effects of different phenolic acids, which are known to complex iron, were assessed for their trypanocidal activities against Trypanosoma brucei brucei using the alarmaBlue assay. The cell cycle effects of the chelators were determined by flow cytometry and parasite morphological analysis was done by microscopy. Gallic acid was the most potent phenolic acid with an IC50 value of 14.2µM. The compounds showed a dose dependent effect on the cell viability and the mitochondrion membrane potential. There was also a significant loss in kinetoplast and an increase in the S phase of the cell cycle. mRNA sequencing and RT-qPCR data showed an upregulation of almost all the transcripts and a corresponding increase in the iron related genes such as the ribonucleotide reductase and cyclin 2 genes. The chelators also showed moderate toxicity against macrophages. The results throw more light on the possible mechanism of action of the chelators and provide alternative therapeutic approaches in the treatment of African trypanosomiasis which might include interfering with the iron metabolism of the parasite.
AMISIGO, C (2021). Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Bruei. Afribary. Retrieved from https://tracking.afribary.com/works/effects-of-iron-chelators-on-bloodstream-forms-of-trypanosoma-bruei
AMISIGO, CYNTHIA "Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Bruei" Afribary. Afribary, 14 Apr. 2021, https://tracking.afribary.com/works/effects-of-iron-chelators-on-bloodstream-forms-of-trypanosoma-bruei. Accessed 09 Nov. 2024.
AMISIGO, CYNTHIA . "Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Bruei". Afribary, Afribary, 14 Apr. 2021. Web. 09 Nov. 2024. < https://tracking.afribary.com/works/effects-of-iron-chelators-on-bloodstream-forms-of-trypanosoma-bruei >.
AMISIGO, CYNTHIA . "Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Bruei" Afribary (2021). Accessed November 09, 2024. https://tracking.afribary.com/works/effects-of-iron-chelators-on-bloodstream-forms-of-trypanosoma-bruei