TY - JOUR
T1 - Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis
AU - Pereira, Isabela A.G.
AU - Mendonça, Débora V.C.
AU - Tavares, Grasiele S.V.
AU - Lage, Daniela P.
AU - Ramos, Fernanda F.
AU - Oliveira-da-Silva, João A.
AU - Antinarelli, Luciana M.R.
AU - Machado, Amanda S.
AU - Carvalho, Lívia M.
AU - Carvalho, Ana Maria R.S.
AU - Salustiano, Iorrana V.
AU - Reis, Thiago A.R.
AU - Bandeira, Raquel S.
AU - Silva, Alessandra M.
AU - Martins, Vívian T.
AU - Chávez-Fumagalli, Miguel A.
AU - Humbert, Maria V.
AU - Roatt, Bruno M.
AU - Duarte, Mariana C.
AU - Menezes-Souza, Daniel
AU - Coimbra, Elaine S.
AU - Leite, João Paulo V.
AU - Coelho, Eduardo A.F.
AU - Gonçalves, Denise U.
N1 - Publisher Copyright:
© 2020 John Wiley & Sons Ltd
PY - 2020/12
Y1 - 2020/12
N2 - Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and Results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4’-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.
AB - Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and Results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4’-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.
KW - delivery systems
KW - flavonoids
KW - immune response
KW - leishmaniasis
KW - miltefosine
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85089975140&partnerID=8YFLogxK
U2 - 10.1111/pim.12784
DO - 10.1111/pim.12784
M3 - Article
C2 - 32772379
AN - SCOPUS:85089975140
SN - 0141-9838
VL - 42
JO - Parasite Immunology
JF - Parasite Immunology
IS - 12
M1 - e12784
ER -