Drug-induced reactive oxygen species-mediated inhibitory effect on growth ofTrypanosoma evansiin axenic culture system

Trypanosoma evansi, an extracellular haemoflagellate, has a wide range of hosts receptive and susceptible to infection, in which it revealed highly inconsistent clinical effects. Drugs used for the treatment of trypanosomosis have been utilized for more than five decades and have several problems like local and systemic toxicity. In the present investigation, imatinib and sorafenib were selected as drugs as they are reported to have the potential to cause reactive oxygen species (ROS)-mediated effect in cancer cells. Both have also been reported to have potential againstT. brucei,T. cruziandLeishmania donovani. To date, imatinib and sorafenib have not evaluated for their growth inhibitory effect againstT. evansi. Imatinib and sorafenib showed significant (p < 0.001) inhibition on parasite growth and multiplication with IC50(50% inhibitory concentration) values 6.12 mu M and 0.33 mu M respectively againstT. evansi. Both the drug molecules demonstrated for the generation of ROS inT. evansiand were found up to 65% increased level of ROS as compared with negative control in the axenic culture system. Furthermore, different concentrations of imatinib and sorafenib were found non-toxic on horse peripheral blood mononuclear cells and Vero cell lines. Also, in conclusion, our results demonstrated that imatinib- and sorafenib-induced generation of ROS contributed inhibitory effect on the growth ofTrypanosoma evansiin an axenic culture system.