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Original Article

A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica

Mahshid Mostafavi1, Payam Khazaeli2,*, Iraj Sharifi1, Saeedeh Farajzadeh3, Hamid Sharifi4, Alireza Keyhani1, Maryam Hakimi Parizi1, Sina Kakooei1
The Korean Journal of Parasitology 2019;57(1):1-8.
Published online: February 26, 2019

1Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran

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*Corresponding author (Khazaeli.payam97@gmail.com)
• Received: October 27, 2018   • Revised: January 16, 2019   • Accepted: January 22, 2019

Copyright © 2019 by The Korean Society for Parasitology and Tropical Medicine

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A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica
Korean J Parasitol. 2019;57(1):1-8.   Published online February 26, 2019
DOI: https://doi.org/10.3347/kjp.2019.57.1.1
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A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica
Korean J Parasitol. 2019;57(1):1-8.   Published online February 26, 2019
DOI: https://doi.org/10.3347/kjp.2019.57.1.1
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A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica
Image Image Image Image
Fig. 1 Microscopic images of Span/Tween 40 (molar ratio=5:5) selenium niosome (A), and Span/Tween 40 (molar ratio=5:5) selenium plus glucantime niosome (B).
Fig. 2 Comparison of inhibitory effect selenium, selenium niosome, selenium plus glucantime niosome and glucantime plus selenium niosome, on Leishmania tropica promastigotes with glucantime as a standard drug, by MTT assay (*P<0.05).
Fig. 3 Inhibitory effect of selenium plus glucantime on promastigotes of Leishmania tropica.
Fig. 4 The gene expression profiles of (A) metacaspase, (B) IL-10, and (C) IL-12p40 on the Leishmania tropica treated by the selenium plus glucantime niosome and glucantime in comparison with untreated control (*P<0.001) as measured by using real-time PCR.

Fig. 1

Fig. 2

Fig. 3

Fig. 4

A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica

Primers which were used for real-time PCR

Primers Gene Forward Sequence (5′-3′) Reverse Sequence (5′-3′) Product size (bp)
Macrophages murine cells IL-12 P40 CTGGAGCACTCCCCATTCCTA GCAGACATTCCCGCCTTTG 160
IL-10 CTTACTGACTGGCATGAGGATCA GCAGCTCTAGGAGCATGTGC 101
GAPDH AGCTTCGGCACATATTTCATCTG CGTTCACTCCCATGACAAACA 89
Promastigotes of L. tropica Metacaspase CAGCAACAATTCCTGGCGATA AAGTTTGAAGTAAAAGGAGACAATTTGG 140
RPS18 Ribosomal protein (S18) GTTGAGGTGCGTGGTCTGTC TGCAGGTTGCTCAGGAGCTT 166

Comparison of the IC50 values of selenium, selenium niosome, glucantime, glucantime plus selenium niosome and selenium plus glucantime niosome on Leishmania tropica promastigotes and amastigotes, CC50 values of drugs on macrophage and SI index

Drug Amastigote Promastigote Macrophage SI
IC50±SD (μg/ml) P-value IC50±SD (μg/ml) P-value CC50 (μg/ml) (Selectivity Index)
Glucantime 222.31±28.04 ≤0.001 144.5±97.3 ≤0.001 1634 7.35
Selenium 216.18±2.82 ≤0.001 78.07±5 ≤0.001 260.51 1.2
Selenium niosome 78.45±1.3 ≤0.001 48.2±6.2 ≤0.001 1202 15.32
Selenium plus glucantime niosome 8.67±0.1 ≤0.001 16.11±0.99 ≤0.001 1105 127.45
Glucantime plus selenium niosome 14.47±2.22 ≤0.001 42.17±2.47 ≤0.001 1511 104.42

IC50, Concentration of drug that caused 50% of growth inhibition of promastigotes and amastigotes; CC50, Concentration of drug that caused 50% of cytotoxicity on macrophages; SI (Selectivity index), the ratio between CC50 on J774 cells and IC50 against L. tropica amastigotes (SI=CC5O/IC50≥10 non-toxic).

Comparison of the overall mean effect of various concentrations of selenium, selenium niosome and, glucantime, selenium plus glucantime niosome, and glucantime plus selenium niosome on the mean number of amastigotes in macrophage

Concentration (μg/ml) Glucantime Selenium Selenium niosome Selenium plus glucantime niosome Glucantime plus selenium niosome
Mean±SD P-value Mean±SD P-value Mean±SD P-value Mean±SD P-value Mean±SD P-value
0 (Untreated control) 22±1 NR 22±0.1 NR 22±1 NR 32±0.56 NR 32±0.56 NR
12.5 21±0.26 0.51 14.7±0.1 ≤0.001 15±0.2 ≤0.001 13.95±0.13 ≤0.001 15.9±0.38 ≤0.001
25 20±0.75 0.51 13.03±0.12 ≤0.001 13±0.7 ≤0.001 13±0.1 ≤0.001 13.84±0.63 ≤0.001
50 15±0.17 ≤0.001 12.37±0.21 ≤0.001 10±0.2 ≤0.001 12.95±0.05 ≤0.001 12.85±0.27 ≤0.001
100 12±0.26 ≤0.001 11.56±0.52 ≤0.001 9±0.05 ≤0.001 11.06±0.19 ≤0.001 10.83±0.35 ≤0.001
200 10±0.62 ≤0.001 8.03±0.14 ≤0.001 8±0.7 ≤0.001 6.32±0.25 ≤0.001 6.45±0.14 ≤0.001

Comparison of the overall mean effect of various concentrations of selenium plus glucantime on the mean number of amastigotes in each macrophage

Concentrations (μg/ml) Glucantime plus selenium
Mean±SD P-value
0 (Untreated control) 36±0.38 NR
50+50 20.4±0.4 ≤0.001
50+100 19.76±0.45 ≤0.001
50+200 18.01±0.4 ≤0.001
100+50 19.7±0.3 ≤0.001
100+100 17.2±0.37 ≤0.001
100+200 13.7±0.46 ≤0.001
200+50 17.07±0.31 ≤0.001
200+100 16.2±0.41 ≤0.001
200+200 13.67±0.5 ≤0.001
Table 1 Primers which were used for real-time PCR
Table 2 Comparison of the IC50 values of selenium, selenium niosome, glucantime, glucantime plus selenium niosome and selenium plus glucantime niosome on Leishmania tropica promastigotes and amastigotes, CC50 values of drugs on macrophage and SI index

IC50, Concentration of drug that caused 50% of growth inhibition of promastigotes and amastigotes; CC50, Concentration of drug that caused 50% of cytotoxicity on macrophages; SI (Selectivity index), the ratio between CC50 on J774 cells and IC50 against L. tropica amastigotes (SI=CC5O/IC50≥10 non-toxic).

Table 3 Comparison of the overall mean effect of various concentrations of selenium, selenium niosome and, glucantime, selenium plus glucantime niosome, and glucantime plus selenium niosome on the mean number of amastigotes in macrophage
Table 4 Comparison of the overall mean effect of various concentrations of selenium plus glucantime on the mean number of amastigotes in each macrophage

Table 1

Table 2

Table 3

Table 4

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