Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism ofLeishmania amazonensispromastigotes

Abstract

AbstractThe anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy inLeishmaniaparasites. Considering the possibility that HIV-PIs induce lipid accumulation inLeishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism ofL. amazonensispromastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition inL. amazonensisin a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI inL. amazonensispromastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.