Send Orders for Print-Reprints and e-prints to reprints@benthamscience.ae Infectious Disorders - Drug Targets, 2018, 18, 1-8 1 RESEARCH ARTICLE 1871-5265/18 $58.00+.00 © 2018 Bentham Science Publishers Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major Lima Asgharpour Sarouey 1 , Parvaneh Rahimi-Moghaddam 2 , Fatemeh Tabatabaie 1,* and Khadijeh Khanaliha 3,* 1 Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 2 Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 3 Research Cen- ter of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sci- ences, Tehran, Iran A R T I C L E H I S T O R Y Received: June 28, 2018 Revised: October 29, 2018 Accepted: November 08, 2018 DOI: 10.2174/1871526518666181113114820 Abstract: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. In this experimental study, four concentrations of the drug (5, 10, 15 and 20 g/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 g/ml and 23.73 g/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 g/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal mod- els of this drug as candidates for cutaneous leishmaniasis therapy. Keywords: Cinnarizine, MTT, Apoptosis, IC50, Cutaneous Leishmaniasis, Leishmania major, Promastigote, Amastigote. 1. INTRODUCTION Leishmaniasis causes various health complications for human populations particularly in endemic regions. The de- velopment of disease depends on many factors such as host immunity and genetic attributes [1-3]. The pentavalent anti- monials such as Glucantime (meglumine antimoniate) and Pentostam (sodium stibogluconate) are the first line drugs *Address correspondence to these authors at Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; E-mails: tabatabaei.f@iums.ac.ir, tabatabaie59@gmail.com and Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; E-mails: khanaliha.kh@iums.ac.ir; khanalihakh@yahoo.com against the disease [4-6]. Many studies have examined me- dicinal herbs, nanoparticles and other chemotherapeutic agents to treat leishmaniasis. Other recent drugs such as liposomal amphotericin B, miltefosine, pentamidine, imiqui- mod, tamoxifen are being examined. Cinnarizine (CNZ) inhibits penetration of parasites into cells by stabilizing cell membrane. H1 antagonist drugs in- hibit mastocyte secretion and release of histamine, chemokine and other vasoactive substances known to be involved in asthma and allergic rhinitis [7]. CNZ(Stugeron ® , Stunarone ® , Arlevert ® ) is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome. CNZ is a calcium ion channel antagonist, antihistaminic, antiserotinergic, anti-