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: Izabela Ono Adriazola, Alex Evangelista do Amaral, Juliana Carolina Amorim, Beatriz Lourenço Correia, Carmen Lúcia Oliveira Petkowicz, Ana Lucia Ramalho Mercê, Guilhermina Rodrigues Noleto
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 132 Pg. 45-51 (Mar 2014) ISSN: 1873-3344 [Electronic] United States
• PMID: 24169303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Antiparasitic Agents
• Coordination Complexes
• Interleukin-1beta
• Interleukin-6
• Mannans
• Vanadium
• galactomannan
• Galactose

Topics

• Animals
• Antiparasitic Agents (chemistry, pharmacology)
• Cells, Cultured
• Coordination Complexes (chemistry, pharmacology)
• Galactose (analogs & derivatives)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Leishmania (drug effects)
• Macrophage Activation (drug effects)
• Mannans (chemistry, pharmacology)
• Mice
• Models, Molecular
• Vanadium (chemistry, pharmacology)