Parasite immunology · 2020
Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Pereira Isabela A G, Mendonça Débora V C, Tavares Grasiele S V, Lage Daniela P, Ramos Fernanda F, Oliveira-da-Silva João A, Antinarelli Luciana M R, Machado Amanda S, Carvalho Lívia M, Carvalho Ana Maria R S, Salustiano Iorrana V, Reis Thiago A R, Bandeira Raquel S, Silva Alessandra M, Martins Vívian T, Chávez-Fumagalli Miguel A, Humbert Maria V, Roatt Bruno M, Duarte Mariana C, Menezes-Souza Daniel, Coimbra Elaine S, Leite João Paulo V, Coelho Eduardo A F, Gonçalves Denise U
Аннотация
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.
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.