Pub Date : 2025-09-01Epub Date: 2025-05-14DOI: 10.1016/j.molbiopara.2025.111679
Vinícius Menezes Tunholi-Alves , Victor Menezes Tunholi , Ludimila Santos Amaral , Natânia do Carmo Sperandio , Lorena Souza Castro Altoé , Melissa Carvalho Machado do Couto-Chambarelli , Caio Márcio de Oliveira Monteiro , Isabella Vilhena Freire Martins
The present study investigated for the first time the influence of exposure time (24 or 48 h) of Biomphalaria glabrata (Gastropoda: Pulmonata) to Heterorhabditis bacteriophora (Rhabditida: Heterorhabditidae), strain HP88, on some physiological and reproductive parameters of the host mollusk. Throughout the experiment, intense glycogenolysis was observed in both exposed groups, which was more accentuated in the digestive gland. This change was accompanied by a significant increase in the free glucose content in the exposed snails, indicating that H. bacteriophora infection induces the breakdown of host glycemic homeostasis. In parallel, significant variations in lactate dehydrogenase activity in the hemolymph of B. glabrata exposed to entomopathogenic nematodes were observed, confirming the transition from aerobic to anaerobic metabolism in the hosts. This physiological scenario contributed to the establishment of the parasitic castration process in this interface, compromising the reproductive performance of host snails, suggesting the use of H. bacteriophora HP88 as a potential alternative for control of B. glabrata.
{"title":"Biological and physiological changes of Biomphalaria glabrata infected by Heterorhabditis bacteriophora","authors":"Vinícius Menezes Tunholi-Alves , Victor Menezes Tunholi , Ludimila Santos Amaral , Natânia do Carmo Sperandio , Lorena Souza Castro Altoé , Melissa Carvalho Machado do Couto-Chambarelli , Caio Márcio de Oliveira Monteiro , Isabella Vilhena Freire Martins","doi":"10.1016/j.molbiopara.2025.111679","DOIUrl":"10.1016/j.molbiopara.2025.111679","url":null,"abstract":"<div><div>The present study investigated for the first time the influence of exposure time (24 or 48 h) of <em>Biomphalaria glabrata</em> (Gastropoda: Pulmonata) to <em>Heterorhabditis bacteriophora</em> (Rhabditida: Heterorhabditidae), strain HP88, on some physiological and reproductive parameters of the host mollusk. Throughout the experiment, intense glycogenolysis was observed in both exposed groups, which was more accentuated in the digestive gland. This change was accompanied by a significant increase in the free glucose content in the exposed snails, indicating that <em>H. bacteriophora</em> infection induces the breakdown of host glycemic homeostasis. In parallel, significant variations in lactate dehydrogenase activity in the hemolymph of <em>B. glabrata</em> exposed to entomopathogenic nematodes were observed, confirming the transition from aerobic to anaerobic metabolism in the hosts. This physiological scenario contributed to the establishment of the parasitic castration process in this interface, compromising the reproductive performance of host snails, suggesting the use of <em>H. bacteriophora</em> HP88 as a potential alternative for control of <em>B. glabrata</em>.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"263 ","pages":"Article 111679"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-05-23DOI: 10.1016/j.molbiopara.2025.111686
Iman F. Abou-El-Naga
Calcium/calmodulin-dependent protein kinase II (CaMKII) performs diverse essential functions through integrating a range of calcium signals. In Schistosoma, two Calmodulin (CaM) genes are characterized. CaMKII exhibits distinct expression patterns across the developmental stages of the parasite. Its significance lies in sustaining Schistosoma survival and maintaining calcium homeostasis. As it is a calcium sensing protein, its function is closely related to the efficacy of praziquantel, the mainstay drug against schistosomiasis. The relationship between CaMKII and praziquantel involves several potential factors. Praziquantel induces an increased calcium influx into Schistosoma that binds CaM and activates CaMKII, which in turn mitigates the effect of the drug and potentially contributes to praziquantel resistance in several ways. By maintaining calcium homeostasis, CaMKII opposes the surge in calcium influx induced by praziquantel. It modulates voltage-gated calcium channels and reduces calcium influx. It also inhibits ryanodine receptors and inositol triphosphate receptors, thus preventing the release of calcium from the sarcoplasmic/endoplasmic reticulum. CaMKII activates nuclear factor-κB and subsequently activates sarco/endoplasmic reticulum calcium-ATPase (SERCA), which increases calcium uptake into the sarcoplasmic/endoplasmic reticulum and decreases cytosolic calcium. Nuclear factor-κB, activated by CaMKII may lead to up-regulation of P-glycoprotein, which facilitates praziquantel efflux. CaMKII also activates calcineurin that inhibits SERCA. Given its pivotal role in Schistosoma homeostasis and survival, CaMKII emerges as a promising target for novel anthelmintic therapies, and its modulation might enhance the efficacy of praziquantel.
{"title":"Calcium/calmodulin-dependent protein kinase II in Schistosoma: Relation to praziquantel action and resistance","authors":"Iman F. Abou-El-Naga","doi":"10.1016/j.molbiopara.2025.111686","DOIUrl":"10.1016/j.molbiopara.2025.111686","url":null,"abstract":"<div><div>Calcium/calmodulin-dependent protein kinase II (CaMKII) performs diverse essential functions through integrating a range of calcium signals. In <em>Schistosoma</em>, two Calmodulin (CaM) genes are characterized. CaMKII exhibits distinct expression patterns across the developmental stages of the parasite. Its significance lies in sustaining <em>Schistosoma</em> survival and maintaining calcium homeostasis. As it is a calcium sensing protein, its function is closely related to the efficacy of praziquantel, the mainstay drug against schistosomiasis. The relationship between CaMKII and praziquantel involves several potential factors. Praziquantel induces an increased calcium influx into <em>Schistosoma</em> that binds CaM and activates CaMKII, which in turn mitigates the effect of the drug and potentially contributes to praziquantel resistance in several ways. By maintaining calcium homeostasis, CaMKII opposes the surge in calcium influx induced by praziquantel. It modulates voltage-gated calcium channels and reduces calcium influx. It also inhibits ryanodine receptors and inositol triphosphate receptors, thus preventing the release of calcium from the sarcoplasmic/endoplasmic reticulum. CaMKII activates nuclear factor-κB and subsequently activates sarco/endoplasmic reticulum calcium-ATPase (SERCA), which increases calcium uptake into the sarcoplasmic/endoplasmic reticulum and decreases cytosolic calcium. Nuclear factor-κB, activated by CaMKII may lead to up-regulation of P-glycoprotein, which facilitates praziquantel efflux. CaMKII also activates calcineurin that inhibits SERCA. Given its pivotal role in <em>Schistosoma</em> homeostasis and survival, CaMKII emerges as a promising target for novel anthelmintic therapies, and its modulation might enhance the efficacy of praziquantel.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"263 ","pages":"Article 111686"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-07-30DOI: 10.1016/j.molbiopara.2025.111690
Qingyang Song , Yihao Yu , Shujing Wang , Hongmei Li , Xiaomin Zhao , Ningning Zhao , Xiao Zhang
Recently, there has been an increased focus on the development of novel anti-parasitic drugs that exhibit both highly efficacy and low toxicity due to growing concerns associated with the widespread use of such drugs. Natural products have garnered significant interest owing to their diverse biological activities and minimal adverse effects. In this study, we assessed the anti-Eimeria tenella activity of four plant compounds belonging to the Lamiaceae family, namely Perillyl alcohol, Carvone, Menthone and Perilla aldehyde. Our in vitro experiments demonstrated that all four compounds, particularly Perillyl alcohol, exhibited potent inhibition against sporulation formation of E. tenella oocyst. Furthermore, our in vivo tests revealed that treatment with these four compounds at a dose of 200 mg/kg significantly reduced oocyst shedding as well as cecal lesions and weight loss caused by E. tenella infection, thereby demonstrating moderate anti-E. tenella activity. Notably, Perillyl alcohol displayed the highest efficacy against E. tenella with an anticoccidial index (ACI) value of 161.4. In summary, our findings indicate that these four compounds derived from the Lamiaceae family exhibit anti-E. tenella activity both in vitro and in vivo, with Perillyl alcohol displaying particularly robust inhibitory effects on E. tenella. It is worthy of further investigation to explore its mechanism of action and potential therapeutic applications.
{"title":"Evaluation of the efficacy of Perillyl alcohol in the treatment of Eimeria tenella infection","authors":"Qingyang Song , Yihao Yu , Shujing Wang , Hongmei Li , Xiaomin Zhao , Ningning Zhao , Xiao Zhang","doi":"10.1016/j.molbiopara.2025.111690","DOIUrl":"10.1016/j.molbiopara.2025.111690","url":null,"abstract":"<div><div>Recently, there has been an increased focus on the development of novel anti-parasitic drugs that exhibit both highly efficacy and low toxicity due to growing concerns associated with the widespread use of such drugs. Natural products have garnered significant interest owing to their diverse biological activities and minimal adverse effects. In this study, we assessed the anti-<em>Eimeria tenella</em> activity of four plant compounds belonging to the Lamiaceae family, namely Perillyl alcohol, Carvone, Menthone and Perilla aldehyde. Our <em>in vitro</em> experiments demonstrated that all four compounds, particularly Perillyl alcohol, exhibited potent inhibition against sporulation formation of <em>E. tenella</em> oocyst. Furthermore, our in vivo tests revealed that treatment with these four compounds at a dose of 200 mg/kg significantly reduced oocyst shedding as well as cecal lesions and weight loss caused by <em>E. tenella</em> infection, thereby demonstrating moderate anti-<em>E. tenella</em> activity. Notably, Perillyl alcohol displayed the highest efficacy against <em>E. tenella</em> with an anticoccidial index (ACI) value of 161.4. In summary, our findings indicate that these four compounds derived from the Lamiaceae family exhibit anti-<em>E. tenella</em> activity both <em>in vitro</em> and <em>in vivo</em>, with Perillyl alcohol displaying particularly robust inhibitory effects on <em>E. tenella</em>. It is worthy of further investigation to explore its mechanism of action and potential therapeutic applications.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"263 ","pages":"Article 111690"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-01-28DOI: 10.1016/j.molbiopara.2025.111675
Kayode K. Ojo, Sumiti Vinayak
{"title":"Molecular and biochemical characterization of parasites protein phosphorylation: Emerging trends, challenges and opportunities","authors":"Kayode K. Ojo, Sumiti Vinayak","doi":"10.1016/j.molbiopara.2025.111675","DOIUrl":"10.1016/j.molbiopara.2025.111675","url":null,"abstract":"","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111675"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-04-01DOI: 10.1016/j.molbiopara.2025.111678
Baycan Mor , Arzu Gormez , Berna Demırcı
Leishmania species are intracellular protozoans responsible for causing both cutaneous and visceral infections. In recent years, the prevalence of leishmaniasis, a systemic and chronic disease, has been on the rise. Complement pathway mechanisms, part of the immune response of host organisms against Leishmania species, have not been fully revealed in leishmaniasis, which is very important for public health. This study aimed to explore the role of the complement system, an integral part of the immune response to Leishmania infections, in gerbil (Meriones unguiculatus) models of cutaneous leishmaniasis. This was achieved by assessing the expression levels of complement system genes (MBL-1, MBL-2, C2, and C3) and quantifying the protein levels of MBL-1, C2, and C3. Additionally, the study aimed to conduct biochemical tests, specifically measuring GSH and MDA levels, to detect oxidative stress in response to infection in gerbils. Finally, hematological analyses were performed to evaluate leukocyte counts in the blood. The expression of complement system genes and some complement system proteins were significantly increased in infected gerbils. Oxidative stress was evident, as indicated by reduced GSH levels and increased MDA levels. Additionally, a significant rise in leukocyte counts was observed as a consequence of the infection. The study concluded that complement system pathways are activated in cutaneous leishmaniasis infections. It was also determined that a thorough evaluation of genomic, proteomic, and immunopathological mechanisms is essential for understanding the pathogenesis of the disease.
{"title":"The role of complement system in a gerbil model of cutaneous leishmaniasis","authors":"Baycan Mor , Arzu Gormez , Berna Demırcı","doi":"10.1016/j.molbiopara.2025.111678","DOIUrl":"10.1016/j.molbiopara.2025.111678","url":null,"abstract":"<div><div><em>Leishmania</em> species are intracellular protozoans responsible for causing both cutaneous and visceral infections. In recent years, the prevalence of leishmaniasis, a systemic and chronic disease, has been on the rise. Complement pathway mechanisms, part of the immune response of host organisms against <em>Leishmania</em> species, have not been fully revealed in leishmaniasis, which is very important for public health. This study aimed to explore the role of the complement system, an integral part of the immune response to <em>Leishmania</em> infections, in gerbil (<em>Meriones unguiculatus</em>) models of cutaneous leishmaniasis. This was achieved by assessing the expression levels of complement system genes (<em>MBL-1</em>, <em>MBL-2</em>, <em>C2</em>, and <em>C3</em>) and quantifying the protein levels of MBL-1, C2, and C3. Additionally, the study aimed to conduct biochemical tests, specifically measuring GSH and MDA levels, to detect oxidative stress in response to infection in gerbils. Finally, hematological analyses were performed to evaluate leukocyte counts in the blood. The expression of complement system genes and some complement system proteins were significantly increased in infected gerbils. Oxidative stress was evident, as indicated by reduced GSH levels and increased MDA levels. Additionally, a significant rise in leukocyte counts was observed as a consequence of the infection. The study concluded that complement system pathways are activated in cutaneous leishmaniasis infections. It was also determined that a thorough evaluation of genomic, proteomic, and immunopathological mechanisms is essential for understanding the pathogenesis of the disease.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111678"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-01-26DOI: 10.1016/j.molbiopara.2025.111673
Amal I. El-Refaiy , Nahed S. Amer , Amani Alhejely , Safa H. Qahl , Amira M. Shaban , Amro E. Mohamed , Amira A. Saleh , Abdelnaser A. Badawy , Mohammed A. El-Magd
This study investigated the effect of dandelion (Taraxacum officinale) leaf aqueous extract (DLE) on the immunological response of mice following infection with Schistosoma mansoni. Mice (in groups of 7) were first experimentally infected with S. mansoni and, 6 weeks later, were treated with praziquantel (PZQ) and/or DLE. Control mice were uninfected. In contrast to the untreated group, animals given PZQ and/or DLE exhibited an enhanced immunological response, as indicated by increased serum IFNγ, TNFα, IL4 and IL10 levels, increased numbers of CD4 + and CD25 + cells in blood and spleen and altered expression of apoptosis-related genes (low Bax and caspase3 and high Bcl2) in the spleen. DLE treatment had a significantly bigger impact in all these parameters compared with PZQ alone and combined DLE/PZQ treatment have the largest effect. While DLE treatment alone significantly decreased parasite burden, it did not improve upon the greater protective effect of PZQ, even when given in combination.
{"title":"Impact of dandelion (Taraxacum officinale) leaf aqueous extract on immunological response of mice after Schistosoma mansoni infection","authors":"Amal I. El-Refaiy , Nahed S. Amer , Amani Alhejely , Safa H. Qahl , Amira M. Shaban , Amro E. Mohamed , Amira A. Saleh , Abdelnaser A. Badawy , Mohammed A. El-Magd","doi":"10.1016/j.molbiopara.2025.111673","DOIUrl":"10.1016/j.molbiopara.2025.111673","url":null,"abstract":"<div><div>This study investigated the effect of dandelion (<em>Taraxacum officinale</em>) leaf aqueous extract (DLE) on the immunological response of mice following infection with <em>Schistosoma mansoni</em>. Mice (in groups of 7) were first experimentally infected with <em>S. mansoni</em> and, 6 weeks later, were treated with praziquantel (PZQ) and/or DLE. Control mice were uninfected. In contrast to the untreated group, animals given PZQ and/or DLE exhibited an enhanced immunological response, as indicated by increased serum IFNγ, TNFα, IL4 and IL10 levels, increased numbers of CD4 + and CD25 + cells in blood and spleen and altered expression of apoptosis-related genes (low <em>Bax</em> and caspase3 and high <em>Bcl2</em>) in the spleen. DLE treatment had a significantly bigger impact in all these parameters compared with PZQ alone and combined DLE/PZQ treatment have the largest effect. While DLE treatment alone significantly decreased parasite burden, it did not improve upon the greater protective effect of PZQ, even when given in combination.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111673"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-01-26DOI: 10.1016/j.molbiopara.2025.111674
Cristian Vicson Gomes Pinheiro , Yasmim Mendes Rocha , João Pedro Viana Rodrigues , Gabriel Acácio de Moura , Juliana Ramos de Oliveira , Francisco Dantas Lourenço , Maria Jânia Teixeira , Valentina Nascimento Melo de Oliveira , Ronaldo Nascimento de Oliveira , Wildson Max Barbosa da Silva , Sara Ingrid Caetano Gomes Barbosa , Daniela Ribeiro Alves , Selene Maia de Morais , Roberto Nicolete
Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy. The heterocyclic ring oxadiazole has been documented in the literature to possess various biological activities, including leishmanicidal properties, thus positioning it as a potential candidate for further investigation. This study aims to evaluate the in vitro leishmanicidal activity of an oxadiazole compound (2i), explore its mechanism of action through enzymatic inhibition and molecular docking, assess its antioxidant activity, and conduct an in silico pharmacokinetic prediction. Pharmacokinetic predictions via ADME/TOX modeling revealed that the 2i molecule exhibits good intestinal absorption (92 %), is water-insoluble (-4 log.mol/L) and demonstrates high permeability in Caco-2 cells (1.35 log.Papp10–6cm/s), suggesting potential for oral administration. Metabolic studies indicated that oxadiazole 2i is an inhibitor of cytochrome P450 enzymes CYP1A2 and CYP2C19, necessitating further evaluation of potential drug interactions. Additionally, it did not exhibit hepatotoxicity or cardiotoxicity; however, it demonstrated mutagenic potential in the salmonella reverse mutation test (AMES), which is a genetic method that detects mutagenic chemical agents, thus justifying more complex confirmatory studies. In vitro assays showed that oxadiazole 2i has DPPH (2,2-diphenyl-1-picrylhydrazyl) radical reducing activity, indicating potential antioxidant properties with an IC50 of 12.10 µg/mL. Concerning its leishmanicidal mechanism of action, molecular docking simulations at the active site of acetylcholinesterase demonstrated that the 2i molecule had superior binding energy values compared to the reference drug physostigmine (-7.39 kcal/mol versus −6.66 kcal/mol, respectively). However, the pharmacophore map revealed that physostigmine had more molecular interactions than oxadiazole 2i. In acetylcholinesterase inhibition assays, the 2i molecule exhibited significant inhibitory activity with an IC50 of 11.91 µg/mL, suggesting a mechanism of action that compromises the parasitic membrane. Moreover, the 2i molecule demonstrated significant leishmanicidal activity against L. infantum with an IC50 of 30.86 μM. Cytotoxicity assays on RAW 264.7 macrophages revealed a high CC50 value of 485.5 µM and a selectivity index (SI) of 17.86. Based on these findings, oxadiazole 2i emerges as a promising candidate for further study, offering prospects for more affordable, selective, and less toxic leishmanicidal agents.
{"title":"In Silico and in vitro assessment of anti-leishmania infantum activity of a novel cyclohexyl-1,2,4-oxadiazole derivative","authors":"Cristian Vicson Gomes Pinheiro , Yasmim Mendes Rocha , João Pedro Viana Rodrigues , Gabriel Acácio de Moura , Juliana Ramos de Oliveira , Francisco Dantas Lourenço , Maria Jânia Teixeira , Valentina Nascimento Melo de Oliveira , Ronaldo Nascimento de Oliveira , Wildson Max Barbosa da Silva , Sara Ingrid Caetano Gomes Barbosa , Daniela Ribeiro Alves , Selene Maia de Morais , Roberto Nicolete","doi":"10.1016/j.molbiopara.2025.111674","DOIUrl":"10.1016/j.molbiopara.2025.111674","url":null,"abstract":"<div><div>Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy. The heterocyclic ring oxadiazole has been documented in the literature to possess various biological activities, including leishmanicidal properties, thus positioning it as a potential candidate for further investigation. This study aims to evaluate the <em>in vitro</em> leishmanicidal activity of an oxadiazole compound (2i), explore its mechanism of action through enzymatic inhibition and molecular docking, assess its antioxidant activity, and conduct an <em>in silico</em> pharmacokinetic prediction. Pharmacokinetic predictions via ADME/TOX modeling revealed that the 2i molecule exhibits good intestinal absorption (92 %), is water-insoluble (-4 log.mol/L) and demonstrates high permeability in Caco-2 cells (1.35 log.Papp10–6cm/s), suggesting potential for oral administration. Metabolic studies indicated that oxadiazole 2i is an inhibitor of cytochrome P450 enzymes CYP1A2 and CYP2C19, necessitating further evaluation of potential drug interactions. Additionally, it did not exhibit hepatotoxicity or cardiotoxicity; however, it demonstrated mutagenic potential in the salmonella reverse mutation test (AMES), which is a genetic method that detects mutagenic chemical agents, thus justifying more complex confirmatory studies. <em>In vitro</em> assays showed that oxadiazole 2i has DPPH (2,2-diphenyl-1-picrylhydrazyl) radical reducing activity, indicating potential antioxidant properties with an IC<sub>50</sub> of 12.10 µg/mL. Concerning its leishmanicidal mechanism of action, molecular docking simulations at the active site of acetylcholinesterase demonstrated that the 2i molecule had superior binding energy values compared to the reference drug physostigmine (-7.39 kcal/mol versus −6.66 kcal/mol, respectively). However, the pharmacophore map revealed that physostigmine had more molecular interactions than oxadiazole 2i. In acetylcholinesterase inhibition assays, the 2i molecule exhibited significant inhibitory activity with an IC<sub>50</sub> of 11.91 µg/mL, suggesting a mechanism of action that compromises the parasitic membrane. Moreover, the 2i molecule demonstrated significant leishmanicidal activity against <em>L. infantum</em> with an IC<sub>50</sub> of 30.86 μM. Cytotoxicity assays on RAW 264.7 macrophages revealed a high CC<sub>50</sub> value of 485.5 µM and a selectivity index (SI) of 17.86. Based on these findings, oxadiazole 2i emerges as a promising candidate for further study, offering prospects for more affordable, selective, and less toxic leishmanicidal agents.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111674"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-03-09DOI: 10.1016/j.molbiopara.2025.111677
Hadeer Abd El-hak Rashed , Nahla S. El-Shenawy , Nadia A. El-Fahla
This study investigates the prevalence, severity, and impacts of parasitic infestations in Clarias gariepinus. Additionally, the study assesses the detrimental impacts of parasite infestation on the health condition of affected catfish, focusing on biochemical and histopathological alterations. A total of 160 fish were sampled from local markets. Parasitological examinations involved the dissection of key organs from each fish. The organs were processed and examined microscopically for parasites identified based on morphometric characteristics. Parasitological indices such as prevalence, mean intensity, and abundance were calculated. Fish blood and liver samples were collected to assess hematological and biochemical parameters. Microscopic and ultrastructural examinations identified the gills and liver as highly infected organs, so they were utilized for transmission electron microscopy (TEM). Analysis of catfish tissues unveiled the existence of Cyathocotylid sp. and Prohemistomum vivax, across all organs with dominance noted in the liver, emphasizing their pathogenic significance and notable ability to invade and establish within multiple organs or the immunocompromised response of the host. Meanwhile, Centrocestus formosanus and Quadriacanthus aegyptiacus were exclusively detected in the gills, with an overall parasitic infection rate of 60 %. The present study is one of the few studies documenting Centrocestus sp. in catfish which reflects its ability to spread in new hosts and environments. A novel morphological dimension was recorded for the recovered metacercariae. The hematological, along with the identified lesions from light histological and TEM examinations in heavily infected catfish, indicate the detrimental impact of parasite infiltration on fish health status. Besides the biochemical biomarkers were significantly (p ≤ 0.05) affected by increasing the degree of infection. This study underscores the profound influence of parasitic infestations on the health of C. gariepinus, emphasizing the urgent need for effective management strategies in aquaculture to mitigate these effects, the spread of new pathogens, and ensure the sustainability and productivity of catfish farming. By integrating parasitological, morphological, histopathological, and biochemical analyses, this research provides valuable insights that contribute to better health management strategies in aquaculture and a deeper understanding of parasite biology.
{"title":"Influences of parasitic stress on the health condition of African Catfish (Clarias gariepinus): Biochemical and histopathological alterations","authors":"Hadeer Abd El-hak Rashed , Nahla S. El-Shenawy , Nadia A. El-Fahla","doi":"10.1016/j.molbiopara.2025.111677","DOIUrl":"10.1016/j.molbiopara.2025.111677","url":null,"abstract":"<div><div>This study investigates the prevalence, severity, and impacts of parasitic infestations in <em>Clarias gariepinus</em>. Additionally, the study assesses the detrimental impacts of parasite infestation on the health condition of affected catfish, focusing on biochemical and histopathological alterations. A total of 160 fish were sampled from local markets. Parasitological examinations involved the dissection of key organs from each fish. The organs were processed and examined microscopically for parasites identified based on morphometric characteristics. Parasitological indices such as prevalence, mean intensity, and abundance were calculated. Fish blood and liver samples were collected to assess hematological and biochemical parameters. Microscopic and ultrastructural examinations identified the gills and liver as highly infected organs, so they were utilized for transmission electron microscopy (TEM). Analysis of catfish tissues unveiled the existence of <em>Cyathocotylid sp.</em> and <em>Prohemistomum vivax</em>, across all organs with dominance noted in the liver, emphasizing their pathogenic significance and notable ability to invade and establish within multiple organs or the immunocompromised response of the host. Meanwhile, <em>Centrocestus formosanus</em> and <em>Quadriacanthus aegyptiacus</em> were exclusively detected in the gills, with an overall parasitic infection rate of 60 %. The present study is one of the few studies documenting <em>Centrocestus</em> sp. in catfish which reflects its ability to spread in new hosts and environments. A novel morphological dimension was recorded for the recovered metacercariae. The hematological, along with the identified lesions from light histological and TEM examinations in heavily infected catfish, indicate the detrimental impact of parasite infiltration on fish health status. Besides the biochemical biomarkers were significantly (p ≤ 0.05) affected by increasing the degree of infection. This study underscores the profound influence of parasitic infestations on the health of <em>C. gariepinus</em>, emphasizing the urgent need for effective management strategies in aquaculture to mitigate these effects, the spread of new pathogens, and ensure the sustainability and productivity of catfish farming. By integrating parasitological, morphological, histopathological, and biochemical analyses, this research provides valuable insights that contribute to better health management strategies in aquaculture and a deeper understanding of parasite biology.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111677"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The causative agent of giardiasis in human and animals is the amitochondriate Giardia lamblia. We observed that exposing Giardia trophozoites to MTZ led to an increase in lipid peroxidation compared to the control group, which was expressed in terms of menadione production as it is the marker for lipo-peroxidation. Oxidative stress generated by reactive nitrogen species and peroxidation of membrane phospholipids are positively correlated with the enhanced PLA2 activity in several organisms to produce arachidonic acid (AA). Our data suggested Giardia produces a unique 56 kDa dimeric enzyme called Phospholipase B (gPLB) in contrast to higher eukaryotes which was responsible for the production of intracellular free AA. This free AA either reacylates to the cell membrane or deacylates to further produce prostaglandins. In normal un-induced controlled trophozoites the membrane reacylation process was dominant due the higher level of acyle CoA synthase (ACS) expression over the time. However, under the oxidative stressed condition the intracellular ACS expression was down regulated. This led to the increase in deacylation process. When AA deacylation becomes dominant over AA reacylation in cells, the free AA accumulates intracellularly. One of the lipid autacoids, derived from AA is prostaglandin2 (PGE2). Oxidative stress generated by reactive nitrogen species in trophozoites increased the PGE2 production via prostaglandin synthase over the time with respect to the controlled one.
{"title":"Metronidazole induces prostaglandin E2 formation via arachidonic acid production in protozoan parasite Giardia lamblia","authors":"Rituparna Sarkar , Sanjib Kumar Sardar , Ajanta Ghosal , Tapas Haldar , Koushik Das , Arjun Ghosh , Akash Prasad , Yumiko Saito-Nakano , Shanta Dutta , Tomoyoshi Nozaki , Sandipan Ganguly","doi":"10.1016/j.molbiopara.2025.111676","DOIUrl":"10.1016/j.molbiopara.2025.111676","url":null,"abstract":"<div><div>The causative agent of giardiasis in human and animals is the amitochondriate <em>Giardia lamblia.</em> We observed that exposing <em>Giardia</em> trophozoites to MTZ led to an increase in lipid peroxidation compared to the control group, which was expressed in terms of menadione production as it is the marker for lipo-peroxidation. Oxidative stress generated by reactive nitrogen species and peroxidation of membrane phospholipids are positively correlated with the enhanced PLA2 activity in several organisms to produce arachidonic acid (AA). Our data suggested <em>Giardia</em> produces a unique 56 kDa dimeric enzyme called Phospholipase B (gPLB) in contrast to higher eukaryotes which was responsible for the production of intracellular free AA. This free AA either reacylates to the cell membrane or deacylates to further produce prostaglandins. In normal un-induced controlled trophozoites the membrane reacylation process was dominant due the higher level of acyle CoA synthase (ACS) expression over the time. However, under the oxidative stressed condition the intracellular ACS expression was down regulated. This led to the increase in deacylation process. When AA deacylation becomes dominant over AA reacylation in cells, the free AA accumulates intracellularly. One of the lipid autacoids, derived from AA is prostaglandin2 (PGE2). Oxidative stress generated by reactive nitrogen species in trophozoites increased the PGE2 production via prostaglandin synthase over the time with respect to the controlled one.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111676"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-01-31DOI: 10.1016/j.molbiopara.2025.111672
Sidhant Jain
In this work the relationship between Schistosoma mansoni (Sm) and the induction and progression of colorectal cancer (CRC) is examined. Various clinical studies reviewed here yield inconsistent results, with some reporting no association between Sm infection and CRC and others suggesting a probable to strong association. Here we propose a number of plausible mechanisms whereby Sm infection might contribute to CRC induction and/or progression. These factors are (1) chronic inflammation, (2) exposure to parasite linked antigens and genotoxic products, especially soluble egg antigens (SEAs) and (3) alteration of the intestinal microbiota. These factors probably predispose humans towards CRC and can help in CRC progression however only widespread epidemiological, clinical and pathological studies can firmly establish their role or a complete lack of it.
{"title":"Does Schistosoma mansoni trigger colorectal cancer?","authors":"Sidhant Jain","doi":"10.1016/j.molbiopara.2025.111672","DOIUrl":"10.1016/j.molbiopara.2025.111672","url":null,"abstract":"<div><div>In this work the relationship between <em>Schistosoma mansoni</em> (Sm) and the induction and progression of colorectal cancer (CRC) is examined. Various clinical studies reviewed here yield inconsistent results, with some reporting no association between Sm infection and CRC and others suggesting a probable to strong association. Here we propose a number of plausible mechanisms whereby Sm infection might contribute to CRC induction and/or progression. These factors are (1) chronic inflammation, (2) exposure to parasite linked antigens and genotoxic products, especially soluble egg antigens (SEAs) and (3) alteration of the intestinal microbiota. These factors probably predispose humans towards CRC and can help in CRC progression however only widespread epidemiological, clinical and pathological studies can firmly establish their role or a complete lack of it.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"262 ","pages":"Article 111672"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}