title: Effects of combined therapy with silymarin and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice.
abstract: Leishmania major is resistant to the traditional treatments in many parts of the world. PgpA, a member of (ABC) transporter superfamily, has been identified in Leishmania involved in antimony resistance. Silymarin can inhibit PgpA. The aim of this study was to determine the effect of combined therapy with glucantime and silymarin on Cutaneous Leishmaniasis. The effects of silymarin on response of L. major to glucantime were evaluated with amastigote macrophage and mice model of leishmaniasis. Immediately after injection in mice inoculated into footpads with L. major amastigote, systemic treatment was performed and the size of footpad swelling was measured twice a week. 4 and 8 weeks after the beginning of the treatment, splenic parasite burden was done. Silymarin showed no significant effect on the response of L. major promastigotes to glucantime. 2 formulations (glucantime 25 µm with silymarin 25 µm or 12.5 µm) reduced cell death in amastigote assays. The effect of silymarin on footpad swelling was detected when the combination of low-dose glucantime (20 mg/kg) with 25-50 mg/kg silymarin (especially 50 mg/kg) were used at day 22 of post infection (P<0.05). According to the parasite burden data, use of silymarin in the presence of different doses of glucantime, did not show significant effect compared to glucantime alone. The results of this study suggest that silymarin in conjunction with glucantime may have benefit effects in murine model of cutaneous leishmaniasis.
authors.affiliation: Biotechnology Research Center and School of Pharmacy, Mashhad -University of Medical Sciences, Mashhad, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Jabini
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Jaafari
authors.affiliation: Medical Toxicology Research Centre and Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Vahdati Hasani
authors.affiliation: Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Ghazizadeh
authors.affiliation: Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Khamesipour
authors.affiliation: Medical Toxicology Research Centre and Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: G
authors.initials: G
authors.lastname: Karimi
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination / Q000379:methods; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D009942:Organometallic Compounds; D012838:Silymarin; D008536:Meglumine; D000077485:Meglumine Antimoniate