Study of the Activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis Mansoni in Mice
Identifieur interne : 002C65 ( Pmc/Curation ); précédent : 002C64; suivant : 002C66Study of the Activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis Mansoni in Mice
Auteurs : Andréa Cristina Apolinário Da Silva [Brésil] ; Juliana Kelle De Andrade Lemoine Neves [Brésil] ; João Inácio Irmão [Brésil] ; Vláudia Maria Assis Costa [Brésil] ; Valdênia Maria Oliveira Souza [Brésil] ; Paloma Lys De Medeiros [Brésil] ; Eliete Cavalcanti Da Silva [Brésil] ; Maria Do Carmo Alves De Lima [Brésil] ; Ivan Da Rocha Pitta [Brésil] ; Mônica Camelo Pessoa De Azevedo Albuquerque [Brésil] ; Suely Lins Galdino [Brésil]Source :
- The Scientific World Journal [ 2356-6140 ] ; 2012.
Abstract
Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult
Url:
DOI: 10.1100/2012/520524
PubMed: 22623908
PubMed Central: 3353485
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Study of the Activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis Mansoni in Mice</title>
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<author><name sortKey="Neves, Juliana Kelle De Andrade Lemoine" sort="Neves, Juliana Kelle De Andrade Lemoine" uniqKey="Neves J" first="Juliana Kelle De Andrade Lemoine" last="Neves">Juliana Kelle De Andrade Lemoine Neves</name>
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<author><name sortKey="Irmao, Joao Inacio" sort="Irmao, Joao Inacio" uniqKey="Irmao J" first="João Inácio" last="Irmão">João Inácio Irmão</name>
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<author><name sortKey="Costa, Vlaudia Maria Assis" sort="Costa, Vlaudia Maria Assis" uniqKey="Costa V" first="Vláudia Maria Assis" last="Costa">Vláudia Maria Assis Costa</name>
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<author><name sortKey="Souza, Valdenia Maria Oliveira" sort="Souza, Valdenia Maria Oliveira" uniqKey="Souza V" first="Valdênia Maria Oliveira" last="Souza">Valdênia Maria Oliveira Souza</name>
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<author><name sortKey="Da Silva, Eliete Cavalcanti" sort="Da Silva, Eliete Cavalcanti" uniqKey="Da Silva E" first="Eliete Cavalcanti" last="Da Silva">Eliete Cavalcanti Da Silva</name>
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<author><name sortKey="De Lima, Maria Do Carmo Alves" sort="De Lima, Maria Do Carmo Alves" uniqKey="De Lima M" first="Maria Do Carmo Alves" last="De Lima">Maria Do Carmo Alves De Lima</name>
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<author><name sortKey="Pitta, Ivan Da Rocha" sort="Pitta, Ivan Da Rocha" uniqKey="Pitta I" first="Ivan Da Rocha" last="Pitta">Ivan Da Rocha Pitta</name>
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<author><name sortKey="Albuquerque, Monica Camelo Pessoa De Azevedo" sort="Albuquerque, Monica Camelo Pessoa De Azevedo" uniqKey="Albuquerque M" first="Mônica Camelo Pessoa De Azevedo" last="Albuquerque">Mônica Camelo Pessoa De Azevedo Albuquerque</name>
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<author><name sortKey="Galdino, Suely Lins" sort="Galdino, Suely Lins" uniqKey="Galdino S" first="Suely Lins" last="Galdino">Suely Lins Galdino</name>
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<series><title level="j">The Scientific World Journal</title>
<idno type="ISSN">2356-6140</idno>
<idno type="eISSN">1537-744X</idno>
<imprint><date when="2012">2012</date>
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<front><div type="abstract" xml:lang="en"><p>Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult <italic>Schistosoma mansoni</italic>
worms <italic>in vitro</italic>
. In the first phase of this study, <italic>S. mansoni</italic>
-infected mice were treated, orally, with 100 mg/Kg of the LPSF-PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30) emulsion, and solid dispersion with polyethylene glycol (PEG). In the second phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg. These treatment regimens significantly reduced the number of recovered worms due to increases in the solubility of the compound in this formulation; the greatest reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in the pattern of mature egg compared to immature eggs; however there was a significant increase in the number of dead eggs. Histopathological analysis of liver tissue showed changes in morphological aspects of the hepatic parenchyma with decrease exudative-productive hepatic granuloma stages, although we found no significant differences in IFN-<italic><italic>γ</italic>
</italic>
, IL-4, IL-10, or NO production in response to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a potential candidate in the etiological treatment of schistosomiasis with a possible dampening effect of the granulomatous process.</p>
</div>
</front>
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<author><name sortKey="Keiser, J" uniqKey="Keiser J">J Keiser</name>
</author>
<author><name sortKey="Bos, R" uniqKey="Bos R">R Bos</name>
</author>
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<biblStruct><analytic><author><name sortKey="Utzinger, J" uniqKey="Utzinger J">J Utzinger</name>
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<biblStruct><analytic><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">ScientificWorldJournal</journal-id>
<journal-id journal-id-type="iso-abbrev">ScientificWorldJournal</journal-id>
<journal-id journal-id-type="publisher-id">TSWJ</journal-id>
<journal-title-group><journal-title>The Scientific World Journal</journal-title>
</journal-title-group>
<issn pub-type="ppub">2356-6140</issn>
<issn pub-type="epub">1537-744X</issn>
<publisher><publisher-name>The Scientific World Journal</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22623908</article-id>
<article-id pub-id-type="pmc">3353485</article-id>
<article-id pub-id-type="doi">10.1100/2012/520524</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Study of the Activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis Mansoni in Mice</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>da Silva</surname>
<given-names>Andréa Cristina Apolinário</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Neves</surname>
<given-names>Juliana Kelle de Andrade Lemoine</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Irmão</surname>
<given-names>João Inácio</given-names>
</name>
<xref ref-type="aff" rid="I2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Costa</surname>
<given-names>Vláudia Maria Assis</given-names>
</name>
<xref ref-type="aff" rid="I2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="I3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Souza</surname>
<given-names>Valdênia Maria Oliveira</given-names>
</name>
<xref ref-type="aff" rid="I3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Medeiros</surname>
<given-names>Paloma Lys</given-names>
</name>
<xref ref-type="aff" rid="I4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>da Silva</surname>
<given-names>Eliete Cavalcanti</given-names>
</name>
<xref ref-type="aff" rid="I4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Lima</surname>
<given-names>Maria do Carmo Alves</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pitta</surname>
<given-names>Ivan da Rocha</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Albuquerque</surname>
<given-names>Mônica Camelo Pessoa de Azevedo</given-names>
</name>
<xref ref-type="aff" rid="I2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="I3"><sup>3</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Galdino</surname>
<given-names>Suely Lins</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="I1"><sup>1</sup>
Laboratório de Planejamento e Síntese de Fármacos (LPSF), Universidade Federal de Pernambuco, Avenida Profssors Moraes Rego 1265, Cidade Universitária, 50670-901 Recife, PE, Brazil</aff>
<aff id="I2"><sup>2</sup>
Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Avenida Profssors Moraes Rego 1265, Cidade Universitária, 50670-901 Recife, PE, Brazil</aff>
<aff id="I3"><sup>3</sup>
Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Avenida Profssors Moraes Rego 1265, Cidade Universitária, 50670-901 Recife, PE, Brazil</aff>
<aff id="I4"><sup>4</sup>
Departamento de Histologia e Embriologia, Universidade Federal de Pernambuco, Avenida Profssors Moraes Rego 1265, Cidade Universitária, 50670-901 Recife, PE, Brazil</aff>
<author-notes><corresp id="cor1">*Mônica Camelo Pessoa de Azevedo Albuquerque: <email>jcmonica@globo.com</email>
</corresp>
<fn fn-type="other"><p>Academic Editor: Issa Nebie</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>1</day>
<month>5</month>
<year>2012</year>
</pub-date>
<volume>2012</volume>
<elocation-id>520524</elocation-id>
<history><date date-type="received"><day>31</day>
<month>10</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>29</day>
<month>12</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012 Andréa Cristina Apolinário da Silva et al.</copyright-statement>
<copyright-year>2012</copyright-year>
<license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p>Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult <italic>Schistosoma mansoni</italic>
worms <italic>in vitro</italic>
. In the first phase of this study, <italic>S. mansoni</italic>
-infected mice were treated, orally, with 100 mg/Kg of the LPSF-PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30) emulsion, and solid dispersion with polyethylene glycol (PEG). In the second phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg. These treatment regimens significantly reduced the number of recovered worms due to increases in the solubility of the compound in this formulation; the greatest reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in the pattern of mature egg compared to immature eggs; however there was a significant increase in the number of dead eggs. Histopathological analysis of liver tissue showed changes in morphological aspects of the hepatic parenchyma with decrease exudative-productive hepatic granuloma stages, although we found no significant differences in IFN-<italic><italic>γ</italic>
</italic>
, IL-4, IL-10, or NO production in response to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a potential candidate in the etiological treatment of schistosomiasis with a possible dampening effect of the granulomatous process.</p>
</abstract>
</article-meta>
</front>
<floats-group><fig id="fig1" position="float"><label>Figure 1</label>
<caption><p>IFN-<italic>γ</italic>
(a), IL-4 (b), and nitric oxide (c) production by spleen cells after treatment of <italic>S. mansoni</italic>
-infected mice with LPSF-PT05-PEG. *<italic>P</italic>
< 0.001 in comparison with control.</p>
</caption>
<graphic xlink:href="TSWJ2012-520524.001"></graphic>
</fig>
<fig id="fig2" position="float"><label>Figure 2</label>
<caption><p>Photomicrographs of granuloma stage in the livers of mice infected by <italic>S. mansoni</italic>
. (a) Infected control exhibiting exudative-productive stage granulomas (arrows) with a mature, viable egg in the center of the fibrocellular granulomas. (b) LPSF-PT05-PEG (3 mg/kg per day); micrographs show well-circumscribed small fibrocellular granulomas and marked ovum degeneration (asterisks). (c) LPSF-PT05-PEG (10 mg/kg per day); productive (arrow) and involutional (asterisk) granulomas stage. (d) LPSF-PT05-PEG (30 mg/kg per day). (e) LPSF-PT05-PEG (100 mg/kg per day) involutional stage granulomas (asterisks). H&E, micrographs are at 100x magnification.</p>
</caption>
<graphic xlink:href="TSWJ2012-520524.002"></graphic>
</fig>
<table-wrap id="tab1" position="float"><label>Table 1</label>
<caption><p>Effect of different formulations of LPSF-PT05 on worm burdens and oogram patterns in experimentally infected mice harbouring adult <italic>S. mansoni</italic>
(BH strain).</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1">Group</th>
<th align="center" rowspan="2" colspan="1">Dosing protocols (mg/Kg × day) </th>
<th align="center" colspan="2" rowspan="1">Worm reductions</th>
<th align="center" colspan="3" rowspan="1">% egg developmental stages</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1">Total worms</th>
<th align="center" rowspan="1" colspan="1">Total worms reduction%</th>
<th align="center" rowspan="1" colspan="1">Total Immature</th>
<th align="center" rowspan="1" colspan="1">Mature</th>
<th align="center" rowspan="1" colspan="1">Dead</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Control (7)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">24.60 ± 16.29</td>
<td align="center" rowspan="1" colspan="1">—</td>
<td align="center" rowspan="1" colspan="1">58.88 ± 14.19</td>
<td align="center" rowspan="1" colspan="1">27.80 ± 10.18</td>
<td align="center" rowspan="1" colspan="1">13.33 ± 4.40</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">LPSF-PT05-Tween (7)</td>
<td align="center" rowspan="1" colspan="1">100 × 5</td>
<td align="center" rowspan="1" colspan="1">19.43 ± 7.87</td>
<td align="center" rowspan="1" colspan="1">21.0</td>
<td align="center" rowspan="1" colspan="1">47.50 ± 7.37</td>
<td align="center" rowspan="1" colspan="1">27.93 ± 5.49</td>
<td align="center" rowspan="1" colspan="1">24.58 ± 7.97</td>
</tr>
<tr><td align="left" colspan="7" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Control (5)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">30.43 ± 12.20</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">50.72 ± 6.14</td>
<td align="center" rowspan="1" colspan="1">29.52 ± 4.16</td>
<td align="center" rowspan="1" colspan="1">19.71 ± 5.51</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">LPSF-PT05-Emulsion (5)</td>
<td align="center" rowspan="1" colspan="1">100 × 5</td>
<td align="center" rowspan="1" colspan="1">18.25 ± 2.87</td>
<td align="center" rowspan="1" colspan="1">40.0</td>
<td align="center" rowspan="1" colspan="1">36.10 ± 12.68</td>
<td align="center" rowspan="1" colspan="1">31.67 ± 4.35</td>
<td align="center" rowspan="1" colspan="1">32.23 ± 14.57</td>
</tr>
<tr><td align="left" colspan="7" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Control (5)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">26.50 ± 12.34</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">57.51 ± 1.17</td>
<td align="center" rowspan="1" colspan="1">34.16 ± 3.53</td>
<td align="center" rowspan="1" colspan="1">8.330 ± 2.36</td>
</tr>
<tr><td align="left" rowspan="4" colspan="1">LPSF-PT05-PEG (5)</td>
<td align="center" rowspan="1" colspan="1">100 × 5</td>
<td align="center" rowspan="1" colspan="1">7.80 ± 3.27</td>
<td align="center" rowspan="1" colspan="1">70.5<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">35.34 ± 7.05*</td>
<td align="center" rowspan="1" colspan="1">41.41 ± 3.48</td>
<td align="center" rowspan="1" colspan="1">23.25 ± 5.01<sup>#</sup>
</td>
</tr>
<tr><td align="center" rowspan="1" colspan="1">30 × 5</td>
<td align="center" rowspan="1" colspan="1">14.00 ± 2.08</td>
<td align="center" rowspan="1" colspan="1">47.1<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">49.17 ± 6.06</td>
<td align="center" rowspan="1" colspan="1">24.38 ± 4.87</td>
<td align="center" rowspan="1" colspan="1">26.46 ± 4.66<sup>#</sup>
</td>
</tr>
<tr><td align="center" rowspan="1" colspan="1">10 × 5</td>
<td align="center" rowspan="1" colspan="1">13.80 ± 4.43</td>
<td align="center" rowspan="1" colspan="1">47.9<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">40.59 ± 15.46</td>
<td align="center" rowspan="1" colspan="1">33.33 ± 12.02</td>
<td align="center" rowspan="1" colspan="1">26.10 ± 3.48<sup>#</sup>
</td>
</tr>
<tr><td align="center" rowspan="1" colspan="1">3 × 5</td>
<td align="center" rowspan="1" colspan="1">21.25 ± 3.40</td>
<td align="center" rowspan="1" colspan="1">19.8</td>
<td align="center" rowspan="1" colspan="1">53.76 ± 5.99</td>
<td align="center" rowspan="1" colspan="1">28.33 ± 3.60</td>
<td align="center" rowspan="1" colspan="1">16.66 ± 2.35</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>The values are expressed in means ± SD. *<italic>P</italic>
≤ 0.05, <sup>#</sup>
<italic>P</italic>
≤ 0.01 in comparison to control.</p>
</fn>
<fn><p>Numbers in brackets represent the numbers of mice.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab2" position="float"><label>Table 2</label>
<caption><p>Hepatic granulomas of mice infected by <italic>S.mansoni</italic>
and treated with LPSF/PT05-PEG.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Granuloma stages</th>
<th align="center" rowspan="1" colspan="1">Control</th>
<th align="center" rowspan="1" colspan="1">3 mg/Kg</th>
<th align="center" rowspan="1" colspan="1">10 mg/Kg</th>
<th align="center" rowspan="1" colspan="1">30 mg/Kg</th>
<th align="center" rowspan="1" colspan="1">100 mg/Kg</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Exudative-productive</td>
<td align="center" rowspan="1" colspan="1">22.33 ± 4.16</td>
<td align="center" rowspan="1" colspan="1">15.66 ± 8.50</td>
<td align="center" rowspan="1" colspan="1">8.00 ± 1.70*</td>
<td align="center" rowspan="1" colspan="1">20.66 ± 5.80</td>
<td align="center" rowspan="1" colspan="1">11.00 ± 1.00*</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Involutional</td>
<td align="center" rowspan="1" colspan="1">32.33 ± 12.50</td>
<td align="center" rowspan="1" colspan="1">43.33 ± 16.20</td>
<td align="center" rowspan="1" colspan="1">20.66 ± 7.76</td>
<td align="center" rowspan="1" colspan="1">44.00 ± 11.35</td>
<td align="center" rowspan="1" colspan="1">29.66 ± 9.29</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>Animals per groups (<italic>n</italic>
= 5). The values are expressed in means ± SD. Comparisons were made by Student's <italic>t</italic>
-test (*<italic>P</italic>
≤ 0.05).</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
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