Antileishmanial activity of Hi-antihistamine drugs and cellular alterations in Leishmania (L.) infantum

Author(s)

Mendes, Viviane de Melo ^[1] ; Tempone, Andre Gustavo ^[1] ; Treiger Borborema, Samanta Etel ^[1]

Affiliation

^[1] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Acta Tropica; v. 195, p. 6-14, JUL 2019.
• Web of Science Citations: 1

Abstract

Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown satisfactory results in their treatment. Analyses of antihistaminic drugs have revealed their in vitro and in vivo activity against trypanosomatids. In this way, this study evaluated the antileishmanial activity of H1-antihistamines and identified the cellular alterations in Leishmania (L.) infantum. Cinnarizine, cyproheptadine, and meclizine showed activity against promastigotes with 50% inhibitory concentration (IC50) values between 10-29 mu M. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC50 values between 20-35 mu M. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - > 200 mu M. These drugs depolarized the mitochondria membrane of parasites and caused morphological alterations, including mitochondrial damage, disorganization of the intracellular content, and nuclear membrane detachment. In conclusion, the L. infantum death may be ascribed by the subcellular alterations followed by a pronounced decrease in the mitochondrial membrane potential, indicating dysfunction in the respiratory chain upon Hl-antihistamine treatment. These H1-antihistamines could be used to explore new routes of cellular death in the parasite and the determination of the targets at a molecular level, would contribute to understanding the potential of these drugs as antileishmanial. (AU)

• FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/24908-4 - Evaluation of antileishmanial activity of antihistaminic drugs and identification of cellular alteration related to therapeutic response in Leishmania (Leishmania) infantum
• Grantee: Viviane de Melo Mendes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation