Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against Schistosoma mansoni, induced liver pathology
Identifieur interne : 000588 ( Pmc/Corpus ); précédent : 000587; suivant : 000589Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against Schistosoma mansoni, induced liver pathology
Auteurs : Asmaa M. El-Kady ; Alzahraa Abdelraouf Ahmad ; Tasneem M. Hassan ; Heba E M. El-Deek ; Samer S. Fouad ; Sultan S. AlthagfanSource :
- Infection and Drug Resistance [ 1178-6973 ] ; 2019.
Abstract
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
The murine model of
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.
Although eugenol could not totally eradicate adults of
Url:
DOI: 10.2147/IDR.S196544
PubMed: 30992676
PubMed Central: 6445185
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PMC:6445185Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against <italic>Schistosoma mansoni,</italic> induced liver pathology</title><author><name sortKey="El Kady, Asmaa M" sort="El Kady, Asmaa M" uniqKey="El Kady A" first="Asmaa M" last="El-Kady">Asmaa M. El-Kady</name><affiliation><nlm:aff id="af1-idr-12-709">Department of Medical Parasitology, Faculty of Medicine, South Valley University, Qena 83523, Egypt,<email>Asmaa.elkady@med.svu.edu.eg</email></nlm:aff></affiliation></author><author><name sortKey="Ahmad, Alzahraa Abdelraouf" sort="Ahmad, Alzahraa Abdelraouf" uniqKey="Ahmad A" first="Alzahraa Abdelraouf" last="Ahmad">Alzahraa Abdelraouf Ahmad</name><affiliation><nlm:aff id="af2-idr-12-709">Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</nlm:aff></affiliation></author><author><name sortKey="Hassan, Tasneem M" sort="Hassan, Tasneem M" uniqKey="Hassan T" first="Tasneem M" last="Hassan">Tasneem M. Hassan</name><affiliation><nlm:aff id="af2-idr-12-709">Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</nlm:aff></affiliation></author><author><name sortKey="El Deek, Heba E M" sort="El Deek, Heba E M" uniqKey="El Deek H" first="Heba E M" last="El-Deek">Heba E M. El-Deek</name><affiliation><nlm:aff id="af3-idr-12-709">Department of Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</nlm:aff></affiliation></author><author><name sortKey="Fouad, Samer S" sort="Fouad, Samer S" uniqKey="Fouad S" first="Samer S" last="Fouad">Samer S. Fouad</name><affiliation><nlm:aff id="af4-idr-12-709">Department of Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt</nlm:aff></affiliation></author><author><name sortKey="Althagfan, Sultan S" sort="Althagfan, Sultan S" uniqKey="Althagfan S" first="Sultan S" last="Althagfan">Sultan S. Althagfan</name><affiliation><nlm:aff id="af5-idr-12-709">Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30992676</idno><idno type="pmc">6445185</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445185</idno><idno type="RBID">PMC:6445185</idno><idno type="doi">10.2147/IDR.S196544</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000588</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000588</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against <italic>Schistosoma mansoni,</italic> induced liver pathology</title><author><name sortKey="El Kady, Asmaa M" sort="El Kady, Asmaa M" uniqKey="El Kady A" first="Asmaa M" last="El-Kady">Asmaa M. El-Kady</name><affiliation><nlm:aff id="af1-idr-12-709">Department of Medical Parasitology, Faculty of Medicine, South Valley University, Qena 83523, Egypt,<email>Asmaa.elkady@med.svu.edu.eg</email></nlm:aff></affiliation></author><author><name sortKey="Ahmad, Alzahraa Abdelraouf" sort="Ahmad, Alzahraa Abdelraouf" uniqKey="Ahmad A" first="Alzahraa Abdelraouf" last="Ahmad">Alzahraa Abdelraouf Ahmad</name><affiliation><nlm:aff id="af2-idr-12-709">Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</nlm:aff></affiliation></author><author><name sortKey="Hassan, Tasneem M" sort="Hassan, Tasneem M" uniqKey="Hassan T" first="Tasneem M" last="Hassan">Tasneem M. Hassan</name><affiliation><nlm:aff id="af2-idr-12-709">Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</nlm:aff></affiliation></author><author><name sortKey="El Deek, Heba E M" sort="El Deek, Heba E M" uniqKey="El Deek H" first="Heba E M" last="El-Deek">Heba E M. El-Deek</name><affiliation><nlm:aff id="af3-idr-12-709">Department of Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt</nlm:aff></affiliation></author><author><name sortKey="Fouad, Samer S" sort="Fouad, Samer S" uniqKey="Fouad S" first="Samer S" last="Fouad">Samer S. Fouad</name><affiliation><nlm:aff id="af4-idr-12-709">Department of Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt</nlm:aff></affiliation></author><author><name sortKey="Althagfan, Sultan S" sort="Althagfan, Sultan S" uniqKey="Althagfan S" first="Sultan S" last="Althagfan">Sultan S. Althagfan</name><affiliation><nlm:aff id="af5-idr-12-709">Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia</nlm:aff></affiliation></author></analytic><series><title level="j">Infection and Drug Resistance</title><idno type="eISSN">1178-6973</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><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></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Quansah, E" uniqKey="Quansah E">E Quansah</name></author><author><name sortKey="Sarpong, E" uniqKey="Sarpong E">E Sarpong</name></author><author><name sortKey="Karikari, Tk" uniqKey="Karikari T">TK Karikari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lustigman, S" uniqKey="Lustigman S">S Lustigman</name></author><author><name sortKey="Prichard, Rk" uniqKey="Prichard R">RK 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<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><body><sec sec-type="intro"><title>Introduction</title><p>Schistosomiasis is one of the high-priority neglected tropical diseases recognized by the WHO.<xref rid="b1-idr-12-709" ref-type="bibr">1</xref> This disease remains one of the most prevalent helminthic infections worldwide, as the number of people with active schistosome infections being likely between 391 and 587 million in 78 countries where schistosomiasis is endemic, with an estimated 12,000–200,000 deaths reported annually.<xref rid="b2-idr-12-709" ref-type="bibr">2</xref>,<xref rid="b3-idr-12-709" ref-type="bibr">3</xref> Schistosomiasis is also a major cause of morbidity as it is responsible for causing anemia and significant growth retardation and has educational and nutritional effects not only among children but also among adults living in endemic areas.<xref rid="b4-idr-12-709" ref-type="bibr">4</xref></p><p>Schistosomiasis is caused by blood flukes belonging to the genus <italic>Schistosoma</italic>.<xref rid="b5-idr-12-709" ref-type="bibr">5</xref> The major <italic>Schistosoma</italic> species that infect humans are <italic>S. haematobium</italic>, <italic>S. mansoni</italic>, and <italic>S. japonicum. S. mansoni</italic> inhabits the intestinal venules (in close contact with host humoral and cellular cytotoxic factors) and primarily affects the liver and gut.<xref rid="b6-idr-12-709" ref-type="bibr">6</xref>–<xref rid="b8-idr-12-709" ref-type="bibr">8</xref></p><p>The main pathological lesions of hepatic schistosomiasis result from a granulomatous reaction against schistosome egg deposition at the acute stage of infection, followed by advanced liver fibrosis in chronic infection.<xref rid="b9-idr-12-709" ref-type="bibr">9</xref> The dynamic process of hepatic fibrogenesis in schistosomiasis is a result of massive deposition of extracellular matrix in the periportal spaces, leading to blockage of the portal veins, which results in a series of complications, such as portal hypertension, splenomegaly, portacaval shunting, and gastrointestinal varices.<xref rid="b10-idr-12-709" ref-type="bibr">10</xref> One of the main mesenchymal cells that have an important role in schistosomal granulomatous reaction are hepatic stellate cells (HSCs) that are considered the main source of collagen deposition in liver schistosomiasis.<xref rid="b11-idr-12-709" ref-type="bibr">11</xref> These cells are normally located within the liver sinusoid in the following two forms: quiescent and activated. Quiescent HSCs are responsible for storage of vitamin A in normal liver tissue, whereas activated HSCs exhibit proliferative, contractile, fibrogenic, and myofibroblastic activities during liver fibrosis.<xref rid="b12-idr-12-709" ref-type="bibr">12</xref> Several studies have shown that HSCs can be activated by different means, such as viral infection, parasitic infestation, autoimmune deficiencies, and dietary or chemical causes.<xref rid="b13-idr-12-709" ref-type="bibr">13</xref> Eventually, the persistent fibrosis of chronic schistosomiasis may be one of the risk factors for hepatic cirrhosis and/or hepatic carcinoma with a high mortality rate.<xref rid="b14-idr-12-709" ref-type="bibr">14</xref></p><p>Although chemotherapy effectively eliminates adult worms and prevents egg deposition, few drugs have been developed to reverse existing hepatic fibrosis. Surgical intervention may be the only choice for patients at the chronic and advanced stages of schistosomiasis.<xref rid="b15-idr-12-709" ref-type="bibr">15</xref> Meanwhile, praziquantel (PZQ) is the drug of choice for the management of schistosomiasis, and significant limitations have been developed recently with reports of the emergence of drug-resistant strains of the parasite in some endemic areas such as Kenya and Egypt.<xref rid="b16-idr-12-709" ref-type="bibr">16</xref>,<xref rid="b17-idr-12-709" ref-type="bibr">17</xref> Therefore, many medicinal plants have been studied for antischistosomal potency in addition to antifibrotic effects to be as alternatives for chemotherapy.</p><p>The essential oil eugenol, which is the main constituent of clove (<italic>Syzygium aromaticum</italic>), has been widely used as a flavoring agent for food. This substance also exhibits many pharmacological activities, including antimicrobial, anti-inflammatory, fungicidal, antioxidant, anticar-cinogenic, antiallergic, antimutagenic, and insecticidal properties.<xref rid="b18-idr-12-709" ref-type="bibr">18</xref>–<xref rid="b27-idr-12-709" ref-type="bibr">27</xref></p><p>Several studies have studied the anti-inflammatory role of eugenol and the effect of eugenol on pro-inflammatory cytokine production by macrophages.<xref rid="b28-idr-12-709" ref-type="bibr">28</xref> Studies have shown an inhibitory effect of this compound on prostaglandin synthesis and neutrophil/macrophage chemotaxis in lipopolysaccharide-induced lung injury, preventing nuclear factor-κB (NF-κB) activation and collagen deposition in the lung parenchyma.<xref rid="b29-idr-12-709" ref-type="bibr">29</xref> Additionally, eugenol exhibited reduction in inflammation by decreasing TNF-α levels and neutrophil infiltration during pulmonary infection in animals.<xref rid="b30-idr-12-709" ref-type="bibr">30</xref></p><p>Furthermore, eugenol has high potential as an anti-parasitic agent that can be incorporated into the treatment of many parasitic infections. In vitro studies on eugenol have suggested that this oil has antigiardial, antileishmanial, trypanocidal, and antimalarial activities at high concentrations. Eugenol can be used in combination with standard drugs for increased efficacy, especially against drug-resistant strains. Eugenol has the advantage of being a natural essential oil with fewer side effects than synthetic therapeutics, whereas its activity is concentration-dependent.<xref rid="b30-idr-12-709" ref-type="bibr">30</xref></p><p>To date, the antihelminthic properties of eugenol have not been well studied; hence, the present work aims to evaluate the antischistosomal, anti-inflammatory, and antifibrotic effects of eugenol on <italic>S. mansoni</italic>-infected mice.</p></sec><sec sec-type="materials|methods"><title>Materials and methods</title><sec sec-type="methods"><title>Animals and experimental design</title><p>Twenty-four adult male Balb-c mice, weighing 18–20 g each, were obtained from the Schistosome Biological Supply Program at Theodor Bilharz Research Institute, Imbaba, Giza, Egypt. Mice were infected percutaneously with approximately 100±2 <italic>S</italic>. <italic>mansoni</italic> cercariae by the paddling method.<xref rid="b31-idr-12-709" ref-type="bibr">31</xref> The animals were given access to water and a standard diet, and the health status of the animals was monitored daily.</p></sec><sec sec-type="methods"><title>Experimental design</title><p>The mice were divided into three groups, with eight mice per group as follows: group I was a positive control (infected with <italic>S. mansoni</italic> cercariae but non-treated); group II was infected with <italic>S. mansoni</italic> cercariae and treated with eugenol; and group III was infected with <italic>S. mansoni</italic> cercariae and treated with PZQ. All mice were sacrificed at the end of the eighth week postinfection.</p></sec><sec><title>Treatment of mice</title><p>Eugenol was purchased from Sonwu Biotech Co., Ltd. (Xi ’an, Shaanxi, China) The compound was orally administered at a dose of 500 µg/kg/day from the fifth week postinfection until the end of the experiment. PZQ was administered orally to mice in the seventh week postinfection at a dose of 1,000 mg/kg on two successive days.<xref rid="b32-idr-12-709" ref-type="bibr">32</xref></p></sec><sec><title>Laboratory workup</title><sec><title>Parasitological studies Recovery of adult worms</title><p>On day 56 postinfection, 24 hours after the final treatment, the mice were euthanized by decapitation. Blood samples were collected for serum analysis, and worms were recovered from the portal and mesenteric veins via vascular perfusion.<xref rid="b33-idr-12-709" ref-type="bibr">33</xref></p></sec><sec><title>Oogram pattern determination</title><p>For each sacrificed mouse, small fragments of the small intestine were processed to calculate the percentage of live immature and mature ova and dead ova.<xref rid="b34-idr-12-709" ref-type="bibr">34</xref>,<xref rid="b35-idr-12-709" ref-type="bibr">35</xref></p></sec><sec><title>Intestinal egg count</title><p>After perfusion, a piece of the intestine of each mouse was obtained and processed to determine the number of eggs per gram of tissue.<xref rid="b36-idr-12-709" ref-type="bibr">36</xref>,<xref rid="b37-idr-12-709" ref-type="bibr">37</xref></p></sec><sec><title>Biochemical measurement</title><p>Serum samples were collected to assess the effects of eugenol on mouse livers in comparison to PZQ. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations were measured using commercial kits (Human, Wiesbaden, Germany).</p></sec><sec><title>Histopathological examination</title><p>Liver tissue specimens were obtained from all groups and immediately fixed in 10% buffered formalin for 24 hours and then dehydrated in increasing concentrations of ethanol and processed for paraffin sectioning. Sections (4 µm thick) were deparaffinized, stained with H&E and Masson’s trichrome stain, and examined using an Olympus light microscope. Stained sections were examined to evaluate the area of granuloma formation to assess the extent of hepatic fibrosis and the associated histopathological changes. The number and sizes of the granulomas in different groups were determined at 100× magnification using a digital image analysis system (Leica Qwin 500; Leica Microsystems, Wetzlar, Germany). Only lobular granulomas around schistosome ova or ovum shells in each section were measured. Counting of the granulomas of each specimen was carried out in five successive fields (100×) of different sections that were more than 250 µm apart.</p></sec><sec><title>Immunohistochemical staining</title><p>Immunohistochemical staining was performed using the avidin–biotin immunoperoxidase method. Sections (4 µm thick) were taken from previously prepared paraffin-embedded tissue blocks and mounted on glass slides. Sections were then dewaxed and rehydrated with a graded ethanol series descending to distilled water. Endogenous peroxidase activity was blocked using 6% hydrogen peroxide for 7 minutes. For epitope retrieval, sections were microwaved in citrate buffer (pH 6) for a total of 12 minutes. Sections were incubated with a primary antibody against α-smooth muscle actin (α-SMA) (clone 17H19L35; Thermo Fisher Scientific, Waltham, MA, USA, diluted at 1/100) for 1 hour at room temperature. Secondary staining kits were used according to the manufacturer’s instructions (Thermo Fisher Scientific). Counterstaining was performed with hematoxylin, and then, the sections were examined by light microscopy. Smooth muscle was used as an external positive control. Negative controls were obtained by omitting the primary antibody.</p></sec></sec><sec sec-type="methods"><title>Statistical analysis</title><p>The results were analyzed using the statistical software package SPSS version 16.The data are expressed as mean ± SD or standard error of the mean. Differences between groups were determined using ANOVA and the non-parametric Mann–Whitney test to compare the mean values between treated and control groups for the different variables in the present study. <italic>P</italic>-values <0.05 were regarded as statistically significant.</p></sec><sec><title>Ethical statement</title><p>Experiments on animals were performed in accordance with the ethical animal guidelines and regulations set by the animal care committee of the Faculty of Medicine, South Valley University, and also were in accordance with the internationally accepted principles for laboratory animal use and care. Ethical approval was granted by the Research and Ethics committee of the Faculty of Medicine, South Valley University.</p></sec></sec><sec sec-type="results"><title>Results</title><sec><title>Parasitological parameters</title><p>Analysis of the parasitological parameters (worm burden, egg count per gram of tissue, and oogram pattern) at the end of the eighth week postinfection showed moderate anti-schitosomal effects of eugenol compared to PZQ. As shown in <xref rid="t1-idr-12-709" ref-type="table">Table 1</xref>, mice treated with PZQ yielded no live worms, whereas administration of eugenol significantly reduced the mean worm output upon perfusion by 19.2% compared to that of infected non-treated mice (<italic>P</italic>-value <0.05).</p><p>Egg deposition in the intestinal wall was also affected, where the ova count per gram of intestine was reduced in the mice treated with eugenol and PZQ in comparison with the non-treated control mice by 11.7% and 96%, respectively, which was statistically significant (<italic>P</italic> value < 0.05).</p><p>On the other hand, the oogram patterns of mice treated with eugenol showed no marked difference compared to the control group, which received no treatment, indicating that eugenol had no effect on egg development (<xref rid="t1-idr-12-709" ref-type="table">Table 1</xref>).</p></sec><sec><title>Biochemical examination</title><p>Data are presented as mean ± SD of at least eight independent measurements. <xref rid="t2-idr-12-709" ref-type="table">Table 2</xref> shows the percentage change due to treatment with eugenol or PZQ relative to the infected non-treated control group (<xref rid="t2-idr-12-709" ref-type="table">Table 2</xref>). The results showed a significant increase in ALT and AST activities in the sera of infected non-treated mice. However, the infected treated groups showed significant reduction in liver enzyme levels, especially in the eugenol-treated group (<xref ref-type="fig" rid="f1-idr-12-709">Figures 1</xref> and <xref ref-type="fig" rid="f2-idr-12-709">2</xref>). The measurements of these biochemical markers in different groups were statistically significant (<italic>P</italic> value <0.05).</p></sec><sec><title>Evaluation of pathological changes using H&E-stained sections</title><p>Microscopic examination of sections from control livers showed normal cellular organization of uninfected hepatic lobules, with the typical distribution of hepatic cords around central veins to the periphery of the lobule. The cell cords were separated by narrow blood sinusoids lined by endothelial cells (<xref ref-type="fig" rid="f1-idr-12-709">Figure 1</xref>).</p><p>Histopathological examination of liver sections from the infected non-treated control group showed multiple chronic granulomatous lesions in the hepatic parenchyma. These granulomas were composed of numerous bilharzial ova containing miracidia, which were surrounded by infiltrates of chronic inflammatory cells such as epithelioid cells, lymphocytes, plasma cells, and eosinophils. Granulomas were marked by concentric fibrosis, with many fibroblasts surrounding the trapped ova. Peri-granulomatous hepatocytes showed hydropic degeneration and foci of necrosis. Brownish-black bilharzial pigmentation was also observed in nearby Kupffer cells and sinusoids. Portal tracts exhibited dilated portal veins with some trapped adult worms, chronic inflammatory cell infiltrate, and periportal fibrosis (<xref ref-type="fig" rid="f3-idr-12-709">Figure 3</xref>).</p><p>Histological liver sections from both groups, treated with PZQ and eugenol, showed noticeable improvement compared with the infected non-treated group. This improvement was represented by a reduction in granuloma number and size (<xref rid="t1-idr-12-709" ref-type="table">Table 1</xref>). In addition, these treated groups showed variable degrees of reduction in the number of bilharzial ova, extent of hepatic fibrosis, and amount of chronic inflammatory cells infiltrate.</p><p>Our results showed that the reduction in the mean number of granulomas in both the eugenol- and PZQ-treated groups was significant (<italic>P</italic><0.05) (<xref rid="t1-idr-12-709" ref-type="table">Table 1</xref>). On the other hand, the reduction in the mean diameter of granulomas was significant only in the eugenol-treated group (<xref rid="t1-idr-12-709" ref-type="table">Table 1</xref>).</p></sec><sec><title>Evaluation of the degree of liver fibrosis using Masson’s trichrome-stained sections</title><p>Liver fibrosis was evaluated by Masson’s trichrome staining, with the collagen fibers stained blue and hepatocytes stained red. Sections from control mice showed normal collagen deposition, with a thin layer of collagen fibers in the walls of the central vein and portal tracts (<xref ref-type="fig" rid="f4-idr-12-709">Figure 4</xref>). However, the amount of collagen fiber was significantly increased in the infected non-treated group, which was characterized by marked periportal fibrosis, portal–portal fibrous bridging, and fibrosis around granulomas. Compared with infection alone both the PZQ- and eugenol-treated groups exhibited decreased collagen deposition in the portal tracts and within the granulomas (<xref ref-type="fig" rid="f4-idr-12-709">Figure 4</xref>).</p></sec><sec><title>Immunohistochemical evaluation of α-SMA expression</title><p>Conversion of HSCs into fibroblasts is the key event in the process of liver fibrosis. The expression of α-SMA is commonly used as a hallmark of activated HSCs. In this study, we found that α-SMA was expressed in HSCs, which exhibited a dark brown cytoplasmic staining pattern. The control group exhibited negative expression of α-SMA or expression that was limited to the walls of the central vein. In the infected non-treated control group, intense α-SMA immunostaining was observed in the central and portal tract areas. Both the PZQ- and eugenol-treated groups showed reduced amounts of α-SMA compared with the infected non-treated control group, which was consistent with the degree of fibrosis, indicating inhibition of HSC activation (<xref ref-type="fig" rid="f5-idr-12-709">Figure 5</xref>).</p></sec></sec><sec sec-type="discussion"><title>Discussion</title><p>Chemotherapy is the main strategy in the management of schistosomiasis, and PZQ is considered the drug of choice in treatment.<xref rid="b38-idr-12-709" ref-type="bibr">38</xref> However, it has been observed that the occurrence of reinfection is common due to the increased resistance of the larval stages of <italic>S. mansoni</italic> to schistoso-micide drugs, which is an impending danger.<xref rid="b39-idr-12-709" ref-type="bibr">39</xref>,<xref rid="b40-idr-12-709" ref-type="bibr">40</xref> Therefore, the improvement of potential alternatives for controlling schistosomiasis is very important.<xref rid="b41-idr-12-709" ref-type="bibr">41</xref></p><p>In the present work, we studied the antischistosomal effect of eugenol on <italic>S. mansoni</italic> infection in a mouse model. The eugenol-treated group exhibited reduction in total worm recovery by 19.2% compared to the infected non-treated group. In addition, there was a reduction in egg density in the intestinal walls in the mice groups treated with eugenol and PZQ by 11.7% and 96%, respectively, compared with the control non-treated group. The reduction in egg count may be attributed to a simultaneous reduction in worm burden.<xref rid="b42-idr-12-709" ref-type="bibr">42</xref> However, the oogram patterns of mice treated with eugenol showed no marked difference from the infected non-treated group, indicating that eugenol had no effect on the fecundity of adult worms or on egg development.</p><p>Few studies have investigated the effect of eugenol as an antiparasitic agent with potential lethal effects on the growth, viability, and morphology of different parasites, such as <italic>Giardia lamblia</italic>, <italic>Leishmania donovani</italic>, and <italic>Trypanosoma cruzi</italic>.<xref rid="b43-idr-12-709" ref-type="bibr">43</xref>–<xref rid="b46-idr-12-709" ref-type="bibr">46</xref> Eugenol also exhibited antimalarial activity against the chloroquine-resistant strain <italic>Plasmodium falciparum</italic>.<xref rid="b47-idr-12-709" ref-type="bibr">47</xref> Furthermore, eugenol showed high toxicity against adult <italic>Fasciola gigantica</italic> in all the tested exposure periods in an in vitro study performed by Kumar and Singh.<xref rid="b48-idr-12-709" ref-type="bibr">48</xref> Such potent antihelminthic effects have also been reported against <italic>Haemonchus contortus</italic>, with maximum eclodibility inhibition.<xref rid="b49-idr-12-709" ref-type="bibr">49</xref></p><p>Similar results have been obtained by previous studies that evaluated the effects of different traditional medicinal plants and essential oils on <italic>S. mansoni</italic> infection in vivo. Prophylactic administration and treatment of infected mice with garlic (<italic>Allium sativum</italic>) extract or allicin significantly reduced the mean worm burden (21.88% and 20.33%, respectively) compared to the positive control. Additionally, the oogram patterns and total ova counts in the tissues, compared to the positive control, exhibited significant reductions of 12.59% and 11.42%, respectively.<xref rid="b42-idr-12-709" ref-type="bibr">42</xref> These results were consistent with those of Metwalley<xref rid="b50-idr-12-709" ref-type="bibr">50</xref> and Mahmoud et al,<xref rid="b51-idr-12-709" ref-type="bibr">51</xref> who studied the antischistosomal effects of <italic>A. sativum</italic> and <italic>Nigella sativa</italic> oil. These authors reported moderate antischistosomal effects of these medicinal plants and attributed these results mainly to the anti-inflammatory and immunomodulatory effects of the plants rather than a direct effect on the parasites.</p><p>In fact, biochemical changes such as hepatic enzyme activities, including serum ALT and AST, are considered to be good biomarkers for the assessment of hepatic cell damage caused by heavy schistosome egg deposition and impaired cell membrane permeability.<xref rid="b52-idr-12-709" ref-type="bibr">52</xref>,<xref rid="b53-idr-12-709" ref-type="bibr">53</xref> In the present study, eugenol exhibited considerable anti-inflammatory activities, because it significantly reduced serum hepatic enzyme levels (AST and ALT) comparable to infected non-treated control. These findings are consistent with those reported by Mahmoud et al, <xref rid="b51-idr-12-709" ref-type="bibr">51</xref> Abdel-Hafeez et al,<xref rid="b54-idr-12-709" ref-type="bibr">54</xref> and Metwally et al.<xref rid="b42-idr-12-709" ref-type="bibr">42</xref> These studies reported increased serum ALT, AST, and GGT levels in schistosome-infected patients and experimental animals in the non-treated infected groups. Subsequently, reduction in serum liver enzyme levels has been occurred in the treated groups. The reduction in serum transaminase levels can be explained by either restoration of the oxidant/antioxidant balance due to the administration of antioxidants or anti-inflammatory agents or by reduction in hepatic granuloma size and fibrosis as well as amelioration in necrotic liver tissue in infected treated mice.<xref rid="b53-idr-12-709" ref-type="bibr">53</xref></p><p>In humans, the regulation of liver fibrosis during schistosomiasis may be highly complex, with multiple mediators regulating disease progression. Patients with severe fibrosis express elevated tumor necrosis factor alpha (TNF-α), IL-5, IL-10, and IL-13 levels, whereas patients with mild fibrosis express high levels of IFN-γ.<xref rid="b55-idr-12-709" ref-type="bibr">55</xref>,<xref rid="b56-idr-12-709" ref-type="bibr">56</xref> On the other hand, macrophages may play important role in the immunopathogenesis of schistosomiasis. Actually, macrophages may have dual effects; as initial inflammatory cells, macrophages may support egg sequestration and granuloma development, and at later stages, these cells may assume anti-inflammatory functions during chronic infection by indirect suppression of other inflammatory cells, decreasing the granuloma volume.<xref rid="b57-idr-12-709" ref-type="bibr">57</xref> Therefore, there is need for a therapeutic agent that has immunomodulatory effects that shift the cytokine profile from T helper 2 (Th2)-lymphocyte-mediated immune responses, which are responsible for granuloma formation, to Th1-lymphocyte-mediated immune responses, which are responsible for immune resistance.<xref rid="b42-idr-12-709" ref-type="bibr">42</xref></p><p>The data in the present study showed that the amount of collagen fiber was significantly increased in the infected non-treated group, which was characterized by marked peri-portal fibrosis, portal–portal fibrous bridging, and fibrosis around granulomas, as observed in previous studies.<xref rid="b42-idr-12-709" ref-type="bibr">42</xref>,<xref rid="b58-idr-12-709" ref-type="bibr">58</xref> Meanwhile, infected groups treated with PZQ or eugenol exhibited decreased collagen deposition in the portal tract and within the granulomas, which significantly reduced the granuloma volume, especially in the eugenol-treated group. These results are similar to those of previous studies that attributed this reduction in collagen deposition to decreased infiltration of circulating fibroblasts into the granulomata, affecting collagen synthesis and reducing the levels of procollagen type III, which is responsible for granuloma formation.<xref rid="b42-idr-12-709" ref-type="bibr">42</xref>,<xref rid="b59-idr-12-709" ref-type="bibr">59</xref> To further investigate the cellular mechanism underlying the antifibrotic activity of eugenol, we focused on HSCs, which are liver-resident cells and play an important role in liver fibrosis.<xref rid="b13-idr-12-709" ref-type="bibr">13</xref> Their action started after liver damage, where they activated, proliferated, and underwent a series of transformation process into myofibroblast-like cells that deposit large amounts of connective tissue components, including collagens I and III and α-SMA.<xref rid="b60-idr-12-709" ref-type="bibr">60</xref>,<xref rid="b61-idr-12-709" ref-type="bibr">61</xref> Some studies have highlighted the role of activated HSCs in the process of fibrogenesis in both murine and human schistosomiasis as well as demonstrated the regulatory effect of schistosome antigens on this transdifferentiation process.<xref rid="b12-idr-12-709" ref-type="bibr">12</xref>,<xref rid="b62-idr-12-709" ref-type="bibr">62</xref></p><p>In this study, immunohistochemical analysis of α-SMA was conducted because this protein is a sensitive marker that increases significantly during liver fibrosis.<xref rid="b51-idr-12-709" ref-type="bibr">51</xref> In the infected non-treated control group, intense α-SMA immunostaining was observed in the central and portal tract areas, and the HSCs that expressed this marker were located mainly at the peripheries of granulomatous lesions, which was consistent with other studies on human and mouse models of <italic>S. japonicum</italic> infection.<xref rid="b11-idr-12-709" ref-type="bibr">11</xref>,<xref rid="b58-idr-12-709" ref-type="bibr">58</xref> Both the PZQ- and eugenol-treated groups showed reduction in α-SMA levels compared with the infected non-treated control group, which was consistent with the degree of fibrosis, indicating the inhibition of HSC activation. These data suggest anti-inflammatory and antifibrotic effects of eugenol and PZQ.</p></sec><sec><title>Conclusion</title><p>Based on the data described herein, the present study clarified that eugenol has considerable anti-inflammatory and antifibrotic activities with moderate antihelminthic effects against <italic>S. mansoni</italic> infection compared to the effect of PZQ. There are many factors that influence the effects of eugenol in experimental animal models of schistosomiasis, including the effects on immune host cells, cytotoxicity, routes of administration, and absorption rates of this essential oil. There are many activities and properties of eugenol that remain undiscovered and need to be further investigated to elucidate the antihelminthic properties of eugenol, both in vivo and in vitro.</p></sec></body><back><fn-group><fn><p><bold>Author contributions</bold></p><p>All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.</p></fn><fn fn-type="COI-statement"><p><bold>Disclosure</bold></p><p>he authors report no conflicts of interest in this work.</p></fn></fn-group><ref-list><title>References</title><ref id="b1-idr-12-709"><label>1</label><element-citation publication-type="journal"><person-group 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person-group-type="author"><name><surname>Chang</surname><given-names>D</given-names></name><name><surname>Ramalho</surname><given-names>LN</given-names></name><name><surname>Ramalho</surname><given-names>FS</given-names></name><name><surname>Martinelli</surname><given-names>AL</given-names></name><name><surname>Zucoloto</surname><given-names>S</given-names></name></person-group><article-title>Hepatic stellate cells in human <italic>Schistosomiasis mansoni</italic>: a comparative immunohistochemical study with liver cirrhosis</article-title><source>Acta Trop</source><year>2006</year><volume>97</volume><issue>3</issue><fpage>318</fpage><lpage>323</lpage><pub-id pub-id-type="pmid">16473318</pub-id></element-citation></ref></ref-list></back><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>Pour manipuler ce document sous Unix (Dilib)
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