Macrophage activation and leishmanicidal activity by galactomannan and its oxovanadium (IV/V) complex in vitro

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:VO2+/VO3+) on macrophage activity. GALMAN-A increased nitric oxide levels by similar to 33% at a concentration of 250 mu g/ml, while GALMAN-A:VO2+/VO3+ decreased nitric oxide levels by similar to 33% at a concentration of 50 mu g/ml. Furthermore, GALMAN-A increased interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels by 5.5 and 2.3 times, respectively, at a concentration of 25 mu g/ml; at the same concentration, GALMAN-A:VO2+/VO3+ promoted an increase in IL-1 beta and IL-6 production by 8 and 5.5 times, respectively. However, neither GALMAN-A nor GALMAN-A:VO2+/VO3+ affected tumor necrosis factor alpha (TNF-alpha) or interleukin-10 (IL-10) levels. Importantly, both GALMAN-A and GALMAN-A:VO2+/VO3+ exhibited leishmanicidal activity on amastigotes of Leishmania (L) amazonensis, reaching similar to 60% activity at concentrations of 100 and 25 mu g/ml, respectively. These results indicate that GALMAN-A is three times more potent and its oxovanadium complex is twelve times more potent than Glucantime (300 mu g/ml), which is the drug of choice in leishmaniasis treatment The IC50 value for GALMAN-A:VO2+/VO3+ was 74.4 mu g/ml (0.58 mu g/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. (c) 2013 Elsevier Inc. All rights reserved.