Iron chelation excludes protein synthesis inhibition in the tetracycline management of African trypanosomosis

Abstract

Ribonucleotide reductase, an iron requiring enzyme necessary in the production of deoxyribonucleotides required for replication in cell division and proliferation is induced during the S phase of the cell cycle. We have compared the trypanocidal properties of four antibiotics that show bactericidal activities by destabilizing ribosome-mRNA complex to inhibit protein synthesis. Tetracycline and oxytetracycline that have iron chelating properties extended the lifespan of trypanosome infected rats from 6 and 5 days of control to 15 and 12 days respectively while chloramphenicol and streptomycin that have no iron chelating properties could not extend the lifespan of infected rats. We confirm our earlier report that iron chelation plays a prominent role in the tetracycline management of African trypanosomosis.

Therapeutic properties and serum iron in <i>T. brucei</i> infected rats treated with amodiaquine and mefloquine

“…Various reports [11][12][13][14] have indicated that ironchelation could be a potent means of killing African trypanosomes in vitro and in vivo and the prime suspect as target is the enzyme ribonucleotide reductase (RNR). It has been reported that blood stream forms of trypanosomes increase their transferring uptake from hosts by approximately 3 folds in iron depletion 7,24 .…”

“…Intracellularly, the iron-dependent, cell cycle related enzyme, ribonucleotide reductase plays a central role in cell division and proliferation 8 . This iron-requiring RNR is presented in T. brucei 9,10 and it has been suggested that it can be exploited for the development of cheap antiparasite therapies including African trypanosomiasis [11][12][13][14] . Drugs of the quinine family have also been suggested to have iron-chelating properties 15,16 .…”