Evaluation of Apoptotic and Antileishmanial Activities of Artemisinin on Promastigotes and BALB/C Mice Infected with Leishmania major.
AbstractBackground: In leishmaniasis, some drugs prescribed for treatment have toxic ef-fects and there are reports about drug resistance in some countries. Due to this fact, using herbal drugs such as artemisinin with good efficacy and low toxic effect might be suitable.Methods: We evaluated the apoptotic effect of artemisinin on Leishmania major in vitro and the antileishmanial activities of artemisinin on leishmaniasis in BALB/c mice and at the end INF-γ and IL-4 cytokines levels were detected by ELISA in spleen cell culture supernatants. During treatment the lesion size and survival rate were measured each four and ten days, respectively.Results: Percentage of early and late apoptosis in promastigotes of control group and promastigotes treated with 10, 25, 50 and 100 μg/ml of artemisinin after 48 h were 0.13, 16.04, 41.23, 49.03 and 81.83, respectively. The IFN-γ in ointment treated group were higher than those of other groups (P<0.05). The in vivo results showed that ointment compounds healed the lesions more effectively rather than intraperito-neal injection method (P<0.05). The survival rate of mice 150 days after challenge in treated group with ointment of artemisinin was 66% while all mice in control groups were died.Conclusion: All of in vitro results represented that this drug had antileishmanial ef-fects and these results were confirmed by evaluation effects in vivo condition of leishmaniasis. Interestingly, according to these results it can be concluded that this drug has antileishmanial effects in vitro and in vivo conditions. Artemisinin induces cytotoxic effect on L. major via apoptosis-related mechanism.
Sundar S, Mehta H, Chhabra A, Singha V, Chau-han V, Desjeux P, et al. Amphotericin B colloidal dispersion for the treatment of Indian visceral leishmaniasis. Clin Infect Dis. 2006; 42:608–13.
Van Agtmael MA, Eggelte TA, Van Boxtel CJ. Artemisinin drugs in the treatment of malaria from medicinal herb to registered medication. Trends Pharmacol Sci. 1999; 20:199-205.
Sen R, Ganguly S, Saha P, Chatterjee M Efficacy of artemisinin in experimental Visceral Leishman-iasis. Int J AntimicrobAgents. 2010; 36:43-49.
Scott P. IFN-g modulates the early development of Th1 responses in a murine model of cutaneous leishmaniasis. J Immunol. 1991; 147:3149-155.
Kurtzhals J, Kemp M, Poulsen LK. Interleukin-4 and interferon-gamma production by Leishmania stimulated peripheral blood mononuclear cells from nonexposed individuals. Scand J Immunol. 1995; 41:342-349.
Ebrahimisadr P, Ghaffarifar F, Hassan ZM. In-vitro evaluation of antileishmanial activity and toxicity of artemether with focus on its apoptotic effect. Iran J Pharm Res. 2013; 12: 903-904.
Mortazavi Dehkordi N, Ghaffarifar F, Hasan Z , Esavand Heydari F. In Vitro and In Vivo Studies of Anti leishmanial Effect of Artemether on Leishmania infantum. Jundishapur J Microbiol. 2013; 6(5): e6379DOI: 10.5812/jjm.6379.
Esavan H ydari F, G affarifar F, Soflaei S, Dalimi A. Comparison between in-vitro effect of Ar-temisia sieberi and artemisinin on Leishmania major. Jundishapur J Nat Pharm Prod. 2013; 8(2): 70-75.
Doroodgar A, Arbabi M, Razavi MR, Mohebali M, Sadr F. Treatment of Cutaneous Leish-maniasis in Murine Model by Hydro Alcoholic Essence of Artemisia sieberi. Iran J Arthropod-Borne Dis. 2008; 2(2): 42-47.
Yousefi R, Ghaffarifar F, Dalimi A. The effect of Alkanna tincturia and Peganum harmala extracts on Leishmania major MRHO/ IR/75/ER) in vitro. Iran J Parasitol. 2009; 4:40-7.
Chang KP, DwyerbDM. Leishmania donovani-hamster macrophage interactions in vitro: cell en-try, intracellular survival, and multiplication of amastigotes. J Exp Med. 1978; 147:515-530
Spellberg B. Edwards JE Jr. Type 1/type 2 im-munity in infectious diseases. Clin Infect Dis. 2001; 32: 76-102.
Vercammen D, Declercq W, Vandenabeele P, Van Breusegem F. Are metacaspases caspases? J Cell Biol. 2007; 179(3): 375-380.
Cunningham AC. Parasitic adaptive mechanisms in infection by Leishmania. Exp Mol Pathol. 2002; 72:132-141.
Venuprasad K, Banerjee PP, Chattopadhyay S, Sharma S, Pal S, Parab P, et al. Human neutro-phil-expressed CD28 interacts with macrophage B7 to induce phosphatidylinositol3-kinase-dependent IFN-γ secretion and restriction of Leishmania growth. J Immunol. 2002; 169:920-928.
Murphy ML,Engwerda CR, Gorak PM, Kaye PM. B7-2 blockade enhances T cell responses to Leishmania donovani. J Immunol. 1997; 159:4460-4466.
Pearson R, Steigbigel R. Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes. J Immunol. 1981; 127:1438-43.
Chang KP. Leishmanicidal mechanisms of hu-man polymorphonuclear phagocytes. Am J Trop Med Hyg. 1981a; 30:322-333.
Chang KP. Antibody-mediated inhibition of phagocytosis in Leishmania donovani- human phag-ocyte interactions in vitro. Am J Trop Med Hyg. 1981b; 30: 334-339.
Handman E, Bullen DV. Interaction of Leishma-nia with the host macrophage. Trends Parasitol. 2002; 18:154.
Channon JY, Roberts MB, Blackwell JM A study of the differential respiratory burst activity elicited by promastigotes and amastigotes of Leishmania donovani in murine resident peritoneal macrophag-es. Immunology. 1984; 53: 345-55.
Pearson RD, Harcus JL, Roberts D, Donowitz GR. Differential survival of Leishmania donovani amastigotes in human monocytes. J Immunol. 1983; 131:1994-1999.
Moore KJ, Matlashewski G. Intracellular infec-tion by Leishmania donovani inhibits macrophage apoptosis. J Immunol. 1994; 152:2930-2937.
Mauel J. Macrophage-parasite interactions in Leishmania infections. J Leucocyte Biol. 1990; 47:187-195.
Reiner NE, Ng W, McMaster WR. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage ex-pression of class I and class II major histocom-patibility complex gene products. J Immunol. 1987; 138:1926-1932.
Saha B, Das G,Vohra H, Ganguly NK, Mishra GC. Macrophage-T cell interaction in experi-mental visceral leishmaniasis: failure to express costimulatory molecules on Leishmania-infected macrophages and its implication in the suppres-sion of cell-mediated immunity. Eur J Immunol. 1995; 5:2492-2498.
Pinelli E, Rutten VP, Bruysters M, Moore PF, Ruitenberg EJ. Compensation for decreased ex-pression of B7 molecules on Leishmania infantum-infected canine macrophages results in restoration of parasite-specific T-cell proliferation and gam-ma interferon production. Infect Immun. 1999;67(1):237-43.
Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of inter-feron gamma or interleukin 4 during the res-olution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989; 169:59-72.
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