Meglumine

Meglumine

Meglumine antimoniate-TiO2@Ag nanoparticle combinations reduce toxicity of the drug while enhancing its antileishmanial effect.[Pubmed:28111133]

Acta Trop. 2017 May;169:30-42.

Currently, the treatment of leishmaniasis is increasingly insufficient as current antileishmanial drugs have many disadvantages such as toxic side effects, high cost, and growing drug resistance. In order to overcome these disadvantages, researchers have recently focused on combination therapy by using pentavalent antimonials in conjunction with other antileihmanial compounds. Our previous study found that TiO2@Ag nanoparticles (TiAgNps) demonstrated significant antileishmanial effects. However, a lethal dose of TiAgNps on L. topica promastigotes was found to be toxic for macrophage cells. Moreover, non-toxic concentrations of TiAgNps were ineffective in inhibiting L. topica promastigotes and amastigotes. Thus, we propose the use of TiAgNps in combination with other antileishmanial compounds like Meglumine antimoniate (MA) at non-toxic concentrations, which may increase the efficacies of both agents and decrease their toxicities. Therefore, the aim of this study was to determine in vitro and in vivo antileishmanial efficacies of TiAgNps-MA combinations at non-toxic concentrations and develop a new approach for treatment that lowers the toxicities of pentavalent antimonials to minimal levels and enhances their effectiveness. In vitro screening was performed on L. topica promastigote and amastigote-macropage culture by using MTT assay to determine proliferation, perform infection index analysis, and to conduct a Griess reaction for nitric oxide production, while in vivo antileishmanial assays were applied on Balb/c mice with CL models. The results demonstrated that combinations including TiAgNps and MA at non-toxic concentrations were highly efficacious against both promastigotes and amastigotes, while MA application alone did not show any inhibitory effects. It was determined that combination applications decreased the proliferation of L. topica promastigotes 2- to 5-fold in contrast to use of MA alone, and was dependent on concentrations. Moreover, the use of combinations led to inhibition of L. topica amastigotes at rates ranging between 80% and 95%. Additionally, combinations were found to decrease metabolic activities of each form of the parasite at ranges between 7- to 20-fold, causing programmed-cell death and stimulation of macrophages for intensive production of nitric oxide, which is accepted as an important antileishmanial agent (p<0.05). Furthermore, Sigma FIC analysis demonstrated that the tested combinations composed little additive, but mostly synergistic effects for inhibition of promastigotes and amastigotes. According to in vivo screening results, the combinations displayed high antileishmanial activities by successfully healing lesions and significantly reducing parasite burdens. Combined, these results show that TiAgNps-MA combinations were much more effective than use of MA alone at non-toxic concentrations and they possess high potential for development of new antileishmanial drugs to fight against leishmaniasis.

Effect of hydroalcoholic extract of Echinacea purpurea in combination with meglumine antimoniate on treatment of Leishmania major-induced cutaneous leishmaniasis in BALB/c mice.[Pubmed:28251109]

Int J Appl Basic Med Res. 2017 Jan-Mar;7(1):53-56.

CONTEXT: Progressive resistance of Leishmania parasite to available drugs including, Meglumine antimoniate, has been reported from various regions of the world, especially Iran. AIMS: This study was conducted to evaluate the effect of hydroalcoholic extract of Echinacea purpurea in a combination therapy with glucantime in the treatment of cutaneous leishmaniasis caused by Leishmania major. MATERIALS AND METHODS: Hydroalcoholic extract of E. purpurea was prepared from the plant. Amastigote form of L. major was inoculated to the tail base of thirty mice. After their tails became wounded, mice were divided into six groups. The first group was used as control and the second group received 100 mg/kg of Echinacea extract (orally). The third group was treated by Meglumine antimoniate with dose of 20 mg/kg. Combination therapy was used for group four, five, and six where the mice received a different concentration of extract (100-200 mg/kg) and glucantime (10-20 mg/kg). The size of the cutaneous lesion on tail base was measured regularly. Findings were analyzed by SPSS software and using Kruskal-Wallis test. RESULTS: The sizes of the lesion were increased in all mice of control group by the time. The mean size of lesions in mice receiving the extract and/or receiving the extract along with Meglumine antimoniate was lower than those of control mice, but the differences were not statistically significant (P > 0.05). On the other hand, the differences between the group of mice which received Meglumine antimoniate alone, and the rest of groups were statistically significant (P < 0.05). CONCLUSION: E. purpurea extract in doses which have been used in this study and combination with Meglumine antimoniate was not much effective against L. major in BALB/C mice.