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Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum.
Acta Trop 2019; 195:6-14AT

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 μM. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC50 values between 20-35 μM. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - >200 μM. 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 H1-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.

Authors+Show Affiliations

Center for Parasitology and Mycology, Instituto Adolfo Lutz, Sao Paulo, Brazil.Center for Parasitology and Mycology, Instituto Adolfo Lutz, Sao Paulo, Brazil.Center for Parasitology and Mycology, Instituto Adolfo Lutz, Sao Paulo, Brazil. Electronic address: samanta.borborema@ial.sp.gov.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31002807

Citation

de Melo Mendes, Viviane, et al. "Antileishmanial Activity of H1-antihistamine Drugs and Cellular Alterations in Leishmania (L.) Infantum." Acta Tropica, vol. 195, 2019, pp. 6-14.
de Melo Mendes V, Tempone AG, Treiger Borborema SE. Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum. Acta Trop. 2019;195:6-14.
de Melo Mendes, V., Tempone, A. G., & Treiger Borborema, S. E. (2019). Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum. Acta Tropica, 195, pp. 6-14. doi:10.1016/j.actatropica.2019.04.017.
de Melo Mendes V, Tempone AG, Treiger Borborema SE. Antileishmanial Activity of H1-antihistamine Drugs and Cellular Alterations in Leishmania (L.) Infantum. Acta Trop. 2019;195:6-14. PubMed PMID: 31002807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum. AU - de Melo Mendes,Viviane, AU - Tempone,Andre Gustavo, AU - Treiger Borborema,Samanta Etel, Y1 - 2019/04/16/ PY - 2018/11/22/received PY - 2019/04/08/revised PY - 2019/04/15/accepted PY - 2019/4/20/pubmed PY - 2019/8/8/medline PY - 2019/4/20/entrez KW - Antihistamine KW - Antileishmanial KW - Drug repurposing KW - Histamine H1 antagonist KW - Leishmania infantum KW - Mitochondrion SP - 6 EP - 14 JF - Acta tropica JO - Acta Trop. VL - 195 N2 - 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 μM. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC50 values between 20-35 μM. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - >200 μM. 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 H1-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. SN - 1873-6254 UR - https://www.unboundmedicine.com/medline/citation/31002807/Antileishmanial_activity_of_H1-antihistamine_drugs_and_cellular_alterations_in_Leishmania_(L.)_infantum L2 - https://linkinghub.elsevier.com/retrieve/pii/S0001-706X(18)31507-9 DB - PRIME DP - Unbound Medicine ER -