title: Macrophage activation and leishmanicidal activity by galactomannan and its oxovanadium (IV/V) complex in vitro.
abstract: Compounds that activate macrophage antimicrobial activity are potential targets for treatment of leishmaniasis. The present study investigated the in vitro immunomodulatory effects of a galactomannan (GALMAN-A) isolated from seeds of Mimosa scabrella and its oxovanadium (IV/V) complex (GALMAN-A:VO(2+)/VO(3+)) on macrophage activity. GALMAN-A increased nitric oxide levels by ~33% at a concentration of 250μg/ml, while GALMAN-A:VO(2+)/VO(3+) decreased nitric oxide levels by ~33% at a concentration of 50μg/ml. Furthermore, GALMAN-A increased interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels by 5.5 and 2.3 times, respectively, at a concentration of 25μg/ml; at the same concentration, GALMAN-A:VO(2+)/VO(3+) promoted an increase in IL-1β and IL-6 production by 8 and 5.5 times, respectively. However, neither GALMAN-A nor GALMAN-A:VO(2+)/VO(3+) affected tumor necrosis factor alpha (TNF-α) or interleukin-10 (IL-10) levels. Importantly, both GALMAN-A and GALMAN-A:VO(2+)/VO(3+) exhibited leishmanicidal activity on amastigotes of Leishmania (L.) amazonensis, reaching ~60% activity at concentrations of 100 and 25μg/ml, respectively. These results indicate that GALMAN-A is three times more potent and its oxovanadium complex is twelve times more potent than Glucantime (300μg/ml), which is the drug of choice in leishmaniasis treatment. The IC50 value for GALMAN-A:VO(2+)/VO(3+) was 74.4μg/ml (0.58μg/ml of vanadium). Thus, the significant activation of macrophages and the noted leishmanicidal effect demonstrate the need for further studies to clarify the mechanisms of action of these compounds.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Izabela Ono
authors.initials: IO
authors.lastname: Adriazola
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Alex
authors.initials: A
authors.lastname: Evangelista do Amaral
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Juliana Carolina
authors.initials: JC
authors.lastname: Amorim
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Beatriz Lourenço
authors.initials: BL
authors.lastname: Correia
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Carmen Lúcia Oliveira
authors.initials: CL
authors.lastname: Petkowicz
authors.affiliation: Departamento de Química, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Ana Lucia Ramalho
authors.initials: AL
authors.lastname: Mercê
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: guilherminanoleto@ufpr.br.
authors.forename: Guilhermina Rodrigues
authors.initials: GR
authors.lastname: Noleto
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D005690:Galactose / Q000031:analogs & derivatives; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects*; D008351:Mannans / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D014639:Vanadium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000977:Antiparasitic Agents; D056831:Coordination Complexes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008351:Mannans; D014639:Vanadium; C012990:galactomannan; D005690:Galactose
keywords: Galactomannan; Immunomodulators; Leishmaniasis; Macrophages; Oxovanadium (IV/V) complexes