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Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against Schistosoma mansoni, induced liver pathology

Identifieur interne : 000588 ( Pmc/Curation ); précédent : 000587; suivant : 000589

Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against Schistosoma mansoni, induced liver pathology

Auteurs : Asmaa M. El-Kady ; Alzahraa Abdelraouf Ahmad [Égypte] ; Tasneem M. Hassan [Égypte] ; Heba E M. El-Deek [Égypte] ; Samer S. Fouad [Égypte] ; Sultan S. Althagfan [Arabie saoudite]

Source :

RBID : PMC:6445185

Abstract

Introduction

Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible antischistosomal effect of eugenol on Schistosoma mansoni.

Materials and methods

The murine model of S. mansoni was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined.

Results

Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups.

Conclusion

Although eugenol could not totally eradicate adults of S. mansoni, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol’s role as a promising antifibrotic and a complementary antischistosomal agent.


Url:
DOI: 10.2147/IDR.S196544
PubMed: 30992676
PubMed Central: 6445185

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<p>The murine model of
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<p>Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups.</p>
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<p>Although eugenol could not totally eradicate adults of
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Infect Drug Resist</journal-id>
<journal-id journal-id-type="iso-abbrev">Infect Drug Resist</journal-id>
<journal-id journal-id-type="publisher-id">Infection and Drug Resistance</journal-id>
<journal-title-group>
<journal-title>Infection and Drug Resistance</journal-title>
</journal-title-group>
<issn pub-type="epub">1178-6973</issn>
<publisher>
<publisher-name>Dove Medical Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">30992676</article-id>
<article-id pub-id-type="pmc">6445185</article-id>
<article-id pub-id-type="doi">10.2147/IDR.S196544</article-id>
<article-id pub-id-type="publisher-id">idr-12-709</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against
<italic>Schistosoma mansoni,</italic>
induced liver pathology</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>El-kady</surname>
<given-names>Asmaa M</given-names>
</name>
<xref ref-type="aff" rid="af1-idr-12-709">1</xref>
<xref ref-type="corresp" rid="c1-idr-12-709"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ahmad</surname>
<given-names>Alzahraa Abdelraouf</given-names>
</name>
<xref ref-type="aff" rid="af2-idr-12-709">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hassan</surname>
<given-names>Tasneem M</given-names>
</name>
<xref ref-type="aff" rid="af2-idr-12-709">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>El-Deek</surname>
<given-names>Heba E M</given-names>
</name>
<xref ref-type="aff" rid="af3-idr-12-709">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fouad</surname>
<given-names>Samer S</given-names>
</name>
<xref ref-type="aff" rid="af4-idr-12-709">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Althagfan</surname>
<given-names>Sultan S</given-names>
</name>
<xref ref-type="aff" rid="af5-idr-12-709">5</xref>
</contrib>
</contrib-group>
<aff id="af1-idr-12-709">
<label>1</label>
Department of Medical Parasitology, Faculty of Medicine, South Valley University, Qena 83523, Egypt,
<email>Asmaa.elkady@med.svu.edu.eg</email>
</aff>
<aff id="af2-idr-12-709">
<label>2</label>
Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</aff>
<aff id="af3-idr-12-709">
<label>3</label>
Department of Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</aff>
<aff id="af4-idr-12-709">
<label>4</label>
Department of Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt</aff>
<aff id="af5-idr-12-709">
<label>5</label>
Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia</aff>
<author-notes>
<corresp id="c1-idr-12-709">Correspondence: Asmaa M El-kady, Department of Medical Parasitology, Qena Faculty of Medicine, South Valley University, 83523 Qena, Egypt, Tel +20 10 0224 0877, Email
<email>Asmaa.elkady@med.svu.edu.eg</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>28</day>
<month>3</month>
<year>2019</year>
</pub-date>
<volume>12</volume>
<fpage>709</fpage>
<lpage>719</lpage>
<permissions>
<copyright-statement>© 2019 El-kady et al. This work is published and licensed by Dove Medical Press Limited</copyright-statement>
<copyright-year>2019</copyright-year>
<license>
<license-p>The full terms of this license are available at
<ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link>
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>
). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Introduction</title>
<p>Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible antischistosomal effect of eugenol on
<italic>Schistosoma mansoni</italic>
.</p>
</sec>
<sec>
<title>Materials and methods</title>
<p>The murine model of
<italic>S. mansoni</italic>
was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined.</p>
</sec>
<sec>
<title>Results</title>
<p>Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Although eugenol could not totally eradicate adults of
<italic>S. mansoni</italic>
, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol’s role as a promising antifibrotic and a complementary antischistosomal agent.</p>
</sec>
</abstract>
<kwd-group>
<title>Keywords</title>
<kwd>eugenol</kwd>
<kwd>
<italic>Schistosoma mansoni</italic>
</kwd>
<kwd>praziquantel</kwd>
<kwd>liver enzymes</kwd>
<kwd>hepatic stellate cells</kwd>
<kwd>anti-inflammatory</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="f1-idr-12-709" position="float">
<label>Figure 1</label>
<caption>
<p>Mean level of ALT in different mice groups.</p>
<p>
<bold>Abbreviation:</bold>
ALT, alanine aminotransferase.</p>
</caption>
<graphic xlink:href="idr-12-709Fig1"></graphic>
</fig>
<fig id="f2-idr-12-709" position="float">
<label>Figure 2</label>
<caption>
<p>Mean level of AST in different mice groups.</p>
<p>
<bold>Abbreviation:</bold>
AST, aspartate aminotransferase.</p>
</caption>
<graphic xlink:href="idr-12-709Fig2"></graphic>
</fig>
<fig id="f3-idr-12-709" position="float">
<label>Figure 3</label>
<caption>
<p>Photomicrographs of the liver stained with H&E.</p>
<p>
<bold>Notes:</bold>
(
<bold>A</bold>
) control group, showing normal portal triad along with a normal hepatocytes and the central vein (×100). (
<bold>B</bold>
)Infected untreated group, showing numerous granulomas with bilharzial ova surrounded by numerous chronic inflammatory cells (×100). (
<bold>C</bold>
and
<bold>D</bold>
) Higher power view showed numerous bilharzial ova containing meracedium and brownish black bilharzial pigmentation(straight arrow) and hydropic degeneration in hepatocytes (curved arrow) (×400). (
<bold>E</bold>
) PZQ treated group. (
<bold>F</bold>
) Eugenol treated group, showing reduced size and number of granuloma and decreased amount of bilharzial ova and the chronic inflammatory cells with absence of hydropic changes in hepatocytes (×100).</p>
</caption>
<graphic xlink:href="idr-12-709Fig3"></graphic>
</fig>
<fig id="f4-idr-12-709" position="float">
<label>Figure 4</label>
<caption>
<p>Photomicrographs of the liver stained with Masson trichrome.</p>
<p>
<bold>Notes:</bold>
(
<bold>A</bold>
) Control group, showing normal (typical) distribution of connective tissue (×100). (
<bold>B</bold>
) Infected untreated group, showing granulomatous lesions with condensed fibrous connective tissue in the granuloma and portal tracts (×200). (
<bold>C</bold>
) Portal-portal bridging fibrosis (×100). (
<bold>D</bold>
) Portal tract that showing marked dilatation of portal vein and excess fibrosis (×200). (
<bold>E</bold>
) PZQ treated group. (
<bold>F</bold>
) Eugenol treated group, showing reduced size and number of granuloma with less fibrous tissue in the granuloma and portal tracts (×100).</p>
</caption>
<graphic xlink:href="idr-12-709Fig4"></graphic>
</fig>
<fig id="f5-idr-12-709" position="float">
<label>Figure 5</label>
<caption>
<p>Photomicrographs of the liver stained with Masson trichrome.</p>
<p>
<bold>Notes:</bold>
(
<bold>A</bold>
) Control group, showing normal (typical) distribution of connective tissue (×100). (
<bold>B</bold>
) Infected untreated group, showing granulomatous lesions with condensed fibrous connective tissue in the granuloma and portal tracts (×200). (
<bold>C</bold>
)Portal-portal bridging fibrosis (×100). (
<bold>D</bold>
)-Portal tract that showing marked dilatation of portal vein and excess fibrosis (×200). (
<bold>E</bold>
) PZQ treated group. (
<bold>F</bold>
) Eugenol treated group, showing reduced size and number of granuloma with less fibrous tissue in the granuloma and portal tracts (×100).</p>
</caption>
<graphic xlink:href="idr-12-709Fig5"></graphic>
</fig>
<table-wrap id="t1-idr-12-709" position="float">
<label>Table 1</label>
<caption>
<p>Statistical analysis of the parasitic and histopathological effects of eugenol and praziquantel on
<italic>Schistosoma mansoni</italic>
-infected mice</p>
</caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1"></th>
<th valign="top" align="left" rowspan="1" colspan="1"></th>
<th valign="top" align="left" rowspan="1" colspan="1">Control group</th>
<th valign="top" align="left" rowspan="1" colspan="1">Eugenol</th>
<th valign="top" align="left" rowspan="1" colspan="1">Praziquantel</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="4" valign="top" align="left" colspan="1">Mean worm burden</td>
<td valign="top" align="left" rowspan="1" colspan="1">Male</td>
<td valign="top" align="left" rowspan="1" colspan="1">3.2±1.9</td>
<td valign="top" align="left" rowspan="1" colspan="1">3±1.4</td>
<td valign="top" align="left" rowspan="1" colspan="1">0.0±0.0</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Female</td>
<td valign="top" align="left" rowspan="1" colspan="1">0±0</td>
<td valign="top" align="left" rowspan="1" colspan="1">0±0</td>
<td valign="top" align="left" rowspan="1" colspan="1">0.0±0.0</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Couple</td>
<td valign="top" align="left" rowspan="1" colspan="1">4.7±1.03</td>
<td valign="top" align="left" rowspan="1" colspan="1">3±1.7</td>
<td valign="top" align="left" rowspan="1" colspan="1">0.0±0.0</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Total</td>
<td valign="top" align="left" rowspan="1" colspan="1">7.8±2.3</td>
<td valign="top" align="left" rowspan="1" colspan="1">6.3±2.4</td>
<td valign="top" align="left" rowspan="1" colspan="1">0.0±0.0</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Total worm burden reduction (%)</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1">19.2</td>
<td valign="top" align="left" rowspan="1" colspan="1">100</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Number of ova/gram, mean ± SEM</td>
<td valign="top" align="left" rowspan="1" colspan="1">Intestine</td>
<td valign="top" align="left" rowspan="1" colspan="1">8,929±1,614.3</td>
<td valign="top" align="left" rowspan="1" colspan="1">7,886.6±504.2</td>
<td valign="top" align="left" rowspan="1" colspan="1">354.7±64.9</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Reduction of ova count in tissues (%)</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1">11.7
<xref ref-type="table-fn" rid="tfn1-idr-12-709">*</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">96
<xref ref-type="table-fn" rid="tfn1-idr-12-709">*</xref>
</td>
</tr>
<tr>
<td rowspan="3" valign="top" align="left" colspan="1">Egg developmental stages, mean ± SEM</td>
<td valign="top" align="left" rowspan="1" colspan="1">Immature eggs</td>
<td valign="top" align="left" rowspan="1" colspan="1">50±3.6</td>
<td valign="top" align="left" rowspan="1" colspan="1">51±1.7</td>
<td valign="top" align="left" rowspan="1" colspan="1">0±0</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Mature eggs</td>
<td valign="top" align="left" rowspan="1" colspan="1">42±2.5</td>
<td valign="top" align="left" rowspan="1" colspan="1">43±1</td>
<td valign="top" align="left" rowspan="1" colspan="1">12±2</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Dead ova</td>
<td valign="top" align="left" rowspan="1" colspan="1">6.3±1.2</td>
<td valign="top" align="left" rowspan="1" colspan="1">6±1</td>
<td valign="top" align="left" rowspan="1" colspan="1">88±2</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">GD (µm)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Granuloma in liver tissue</td>
<td valign="top" align="left" rowspan="1" colspan="1">273.25±14.81</td>
<td valign="top" align="left" rowspan="1" colspan="1">203.47±8.08</td>
<td valign="top" align="left" rowspan="1" colspan="1">239.77±6.58</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Reduction in GD (%)</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1">25.54
<xref ref-type="table-fn" rid="tfn1-idr-12-709">*</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">12.26</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Granuloma number</td>
<td valign="top" align="left" rowspan="1" colspan="1">Granuloma in liver tissue</td>
<td valign="top" align="left" rowspan="1" colspan="1">21.38±0.62</td>
<td valign="top" align="left" rowspan="1" colspan="1">13.76±0.26</td>
<td valign="top" align="left" rowspan="1" colspan="1">9.79±0.58</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Reduction in granuloma number (%)</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1">35.65
<xref ref-type="table-fn" rid="tfn1-idr-12-709">*</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">54.21
<xref ref-type="table-fn" rid="tfn1-idr-12-709">*</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>
<bold>Note:</bold>
</p>
</fn>
<fn id="tfn1-idr-12-709">
<label>*</label>
<p>Significant result (
<italic>P</italic>
<0.05).</p>
</fn>
<fn id="tfn2-idr-12-709">
<p>
<bold>Abbreviations:</bold>
GD, granuloma diameter; SEM, standard error of the mean.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t2-idr-12-709" position="float">
<label>Table 2</label>
<caption>
<p>Statistical analysis of the biochemical parameters of the effects of eugenol and praziquantel on
<italic>Schistosoma mansoni</italic>
-infected mice</p>
</caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1"></th>
<th valign="top" align="left" rowspan="1" colspan="1">Examined group</th>
<th valign="top" align="left" rowspan="1" colspan="1">Min</th>
<th valign="top" align="left" rowspan="1" colspan="1">Max</th>
<th valign="top" align="left" rowspan="1" colspan="1">Mean+ Std. Deviation</th>
<th valign="top" align="left" rowspan="1" colspan="1">
<italic>P</italic>
-value</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="4" valign="top" align="left" colspan="1">ALT</td>
<td valign="top" align="left" rowspan="1" colspan="1">Uninfected untreated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">17</td>
<td valign="top" align="left" rowspan="1" colspan="1">36</td>
<td valign="top" align="left" rowspan="1" colspan="1">22.60+7.701</td>
<td rowspan="4" valign="top" align="left" colspan="1">0.043</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Infected untreated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">123</td>
<td valign="top" align="left" rowspan="1" colspan="1">212</td>
<td valign="top" align="left" rowspan="1" colspan="1">153.80+38.564</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Euogenol treated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">33</td>
<td valign="top" align="left" rowspan="1" colspan="1">107</td>
<td valign="top" align="left" rowspan="1" colspan="1">80.00+29.198</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Praziquantel treated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">38</td>
<td valign="top" align="left" rowspan="1" colspan="1">163</td>
<td valign="top" align="left" rowspan="1" colspan="1">109.60+51.699</td>
</tr>
<tr>
<td rowspan="4" valign="top" align="left" colspan="1">AST</td>
<td valign="top" align="left" rowspan="1" colspan="1">Uninfected untreated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">12</td>
<td valign="top" align="left" rowspan="1" colspan="1">29</td>
<td valign="top" align="left" rowspan="1" colspan="1">19.60+6.580</td>
<td rowspan="4" valign="top" align="left" colspan="1">0.020</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Infected untreated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">52</td>
<td valign="top" align="left" rowspan="1" colspan="1">145</td>
<td valign="top" align="left" rowspan="1" colspan="1">96.60+36.624</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Euogenol treated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">19</td>
<td valign="top" align="left" rowspan="1" colspan="1">67</td>
<td valign="top" align="left" rowspan="1" colspan="1">31.80+19.842</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Praziquantel treated group</td>
<td valign="top" align="left" rowspan="1" colspan="1">15</td>
<td valign="top" align="left" rowspan="1" colspan="1">111</td>
<td valign="top" align="left" rowspan="1" colspan="1">52.20+35.478</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn3-idr-12-709">
<p>
<bold>Abbreviations:</bold>
ALT, alanine aminotransferase; AST, aspartate aminotransferase; min, minimum; max, maximum.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>

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