Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/29450
Title: Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes
Authors: Rebello, Karina M.
Andrade Neto, Valter V.
Zuma, Aline A.
Motta, Maria Cristina M.
Gomes, Claudia Regina B.
Souza, Marcus Vinícius N. de
Atella, Geórgia C.
Branquinha, Marta H.
Santos, André L. S.
Santos, Eduardo Caio Torres
d'Avila-Levy, Claudia M.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Síntese de Fármacos. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Síntese de Fármacos. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.
Abstract: The 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 in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. 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 in L. amazonensis in a concentration-response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. 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.
Keywords: Aspartyl
chemotherapy
co-infection
leishmaniasis
trypanosomatids
keywords: Aspartato
Quimioterapia
Leishmaniose
Co-ínfecção
tripanossomatídeos
Issue Date: 2018
Publisher: Cambridge University Press
Citation: REBELLO, Karina M. et al. Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes. Parasitology, v.145, p.1304-1310, May 2018.
DOI: 10.1017/S0031182018000823
ISSN: 0031-1820
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
karina_rebello_etal_IOC_2018.pdf460.66 kBAdobe PDF    Request a copy



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.