Therapeutic properties and serum iron in T. brucei infected rats treated with amodiaquine and mefloquine
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Date
2005
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Published by Nigerian Society For Experimental Biology (NISEB).
Abstract
Serum iron was monitored in Trypanosoma brucei-infected rats treated with Amodiaquine and mefloquine antimalarials as the infection progressed. The chemotherapeutic properties of the drugs against African sleeping sickness were also assessed. Results show gradual reduction in the levels of serum iron in the infected but treated rats as the infection progressed. Results also show that reduction in serum iron level is more pronounced in amodiaquine treated but uninfected rats than the mefloquine treated rats. Serum level in infected but not treated rats increased steadily from the day of infection. For prophylactic treatments of infected rat, amodiaquine extended the lifespan of the rats for 14 days while mefloquine extended it for 7 days. For early stage treatment, amodiaquine and mefloquine extended life span for 7 and 4 days respectively while late stage treatment the extensions were 2 and 1 day respectively. Results suggest that these antimalarials especially amodiaquine could be useful in the clinical management of African sleeping sickness and that this may be through reduction of blood iron level, a situation that can inhibit ribonucleotide reductase of the proliferating parasites.
Description
Iron is an essential nutrient for most bacteria and has been identified as an important factor in the establishment of infections. The effect of trypanosome infection on rats leads to erythrocyte
lyses and anemia. Ribonucleotide reductase is an iron-requiring enzyme which plays a central role in DNA replication, cell division cycle and proliferation. This enzyme provides the deoxyribonucleotide (dNTP) precursors in DNA replication of the cell division cycle. It is the only enzyme along the cell division cycle that requires iron not as part of a prosthetic group but as part of the free iron pool. The recombinant ribonucleotide reductase enzyme of trypanosomes contain iron-tyrosyl free radical centre thus suggesting that the native enzyme could be subjected to regulation through iron deprivation.
Keywords
Amodiaquin, serum iron, T. brucei, mefloquin
Citation
Ekanem, J.T., Sulaiman, F.A. & Adeyemi, O. (2005): Therapeutic properties and serum iron in T. brucei infected rats treated with amodiaquine and mefloquine. Biokemistri. 17(2): 115-121. ISSN: 0795-8080. Published by Nigerian Society For Experimental Biology (NISEB). Available online at https://scholar.google.com/citations?user=32ATmMUAAAAJ&hl=en#d=gs_md_cita-d&u=%2Fcitations%3Fview_op%3Dview_citation%26hl%3Den%26user%3D32ATmMUAAAAJ%26citation_for_view%3D32ATmMUAAAAJ%3A9yKSN-GCB0IC%26tzom%3D-60 and http://www.bioline.org.br/bk