Activity of the antiarrhythmic drug amiodarone against Leishmania (L.) infantum: an in vitro and in vivo approach
Autor: | Andre G. Tempone, Erika G. Pinto |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 030106 microbiology Amiodarone Pharmacology Toxicology 03 medical and health sciences In vitro In vivo lcsh:RA1190-1270 lcsh:Zoology Medicine lcsh:QL1-991 Amastigote IC50 lcsh:Toxicology. Poisons Leishmania Visceral leishmaniasis business.industry Research medicine.disease Drug repositioning 030104 developmental biology Infectious Diseases Toxicity Animal Science and Zoology Parasitology business medicine.drug |
Zdroj: | The Journal of Venomous Animals and Toxins Including Tropical Diseases Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 24, Iss 1, Pp 1-6 (2018) Journal of Venomous Animals and Toxins including Tropical Diseases v.24 2018 The Journal of venomous animals and toxins including tropical diseases Universidade Estadual Paulista (UNESP) instacron:UNESP |
ISSN: | 1678-9199 |
Popis: | Background: Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. Methods: In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.)infantum and its in vitro and in vivo activity. Results: The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Conclusions: Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL. |
Databáze: | OpenAIRE |
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