Effects of linalool and eugenol on the survival of Leishmania (L.) infantum chagasi within macrophages

• Published in: Acta tropica 2016-12, Vol.164, p.69-76
• Main Authors: Dutra, Fernando L., Oliveira, Maurício M., Santos, Reinaldo S., Silva, Wagner Seixas, Alviano, Daniela S., Vieira, Danielle P., Lopes, Angela H.
• Format: Article
• Language: English
• Subjects: Animals; Eugenol; Eugenol - pharmacology; Infectivity; Insecticides - pharmacology; Leishmania; Leishmania infantum - drug effects; Linalool; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - parasitology; Mice, Inbred BALB C; Monoterpenes - pharmacology; Survival
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2016.08.026

[Display omitted] •Eugenol and linalool reduced the intracellular proliferation of amastigotes.•Linalool increased PKA activity only after 4h of treatment in axenic amastigotes.•PKA activity was increased (1h) and reduced (4h) by eugenol in axenic amastigotes.•Eugenol and linalool enhanced PKC activity in axenic amastigotes.•Linalool caused a decrease in L. infantum chagasi oxygen consumption. The most commonly used drugs against visceral leishmaniasis are based on pentavalent antimonial compounds, which have played a fundamental role in therapy for over 70 years. However, the treatment is painful and has severe toxic side effects that can be fatal. Antimonial resistance is spreading and reaching alarming proportions. Linalool and eugenol have been shown to kill Leishmania (L.) amazonensis and Trypanosoma cruzi at low doses. In the present study, we demonstrate the effects of linalool and eugenol, components of essential oils, on Leishmania (L.) infantum chagasi, one of the causative agents of visceral leishmaniasis. We compared the effects of those compounds to the effects of glucantime, a positive control. In L. infantum chagasi killing assays, the LD50 for eugenol was 220μg/ml, and that for linalool was 550μg/ml. L. infantum chagasi was added to cultures of peritoneal mouse macrophages for four hours prior to drug treatment. Eugenol and linalool significantly decreased the number of parasites within the macrophages. Eugenol and linalool enhanced the activities of the L. infantum chagasi protein kinases PKA and PKC. Linalool also decreased L. infantum chagasi oxygen consumption. In conclusion, both linalool and eugenol promoted a decrease in the proliferation and viability of L. infantum chagasi. These effects were more pronounced during the interaction between the parasites and peritoneal mouse macrophages.