Ulcerative colitis (UC) is an inflammatory bowel disease and psychological factors may be one of its pathogeneses. Selective serotonin reuptake inhibitor drug such as paroxetine with an effective anti-depression ability may be a new option for UC treatment. To evaluate the therapeutic effect of paroxetine on the exacerbation of UC symptoms caused by depression, a dual model of C57BL/6 mice was established using dextran sulphate sodium and chronic unpredictable mild stress (CUMS). Behavioural experiments, H&E staining and the level of 5-hydroxytryptamine (5-HT) in the brain were used to demonstrate successful replication of the CUMS model. The levels of 5-HT, TNF-α and IL-1β in the colon and the activity of MPO in the serum were determined by ELISA kits. The levels of some gut microbiota in the faeces were measured by qPCR and faecal differential metabolites were analysed by 1H NMR. The results indicate that CUMS can exacerbate UC symptoms in mice by exacerbating inflammation, and UC+CUMS can disrupt gut microbiota and fatty acid metabolism. Paroxetine can improve the mental state of mice, reduce serum MPO activity, but increase TNF-α and IL-1β levels in the colon. In addition, paroxetine also can restore the intestinal flora of mice and improve intestinal absorption and metabolic function of amino acids and short-chain fatty acids.
{"title":"Paroxetine alleviates ulcerative colitis in mice via restoring intestinal microbiota homeostasis and metabolism","authors":"Minquan Zhang, Yuxin Zhou, Lianghui Huang, Weiman Hong, Yangbiao Li, Zhenhua Chen, Liangliang Zhou","doi":"10.1111/bcpt.14114","DOIUrl":"10.1111/bcpt.14114","url":null,"abstract":"<p>Ulcerative colitis (UC) is an inflammatory bowel disease and psychological factors may be one of its pathogeneses. Selective serotonin reuptake inhibitor drug such as paroxetine with an effective anti-depression ability may be a new option for UC treatment. To evaluate the therapeutic effect of paroxetine on the exacerbation of UC symptoms caused by depression, a dual model of C57BL/6 mice was established using dextran sulphate sodium and chronic unpredictable mild stress (CUMS). Behavioural experiments, H&E staining and the level of 5-hydroxytryptamine (5-HT) in the brain were used to demonstrate successful replication of the CUMS model. The levels of 5-HT, TNF-α and IL-1β in the colon and the activity of MPO in the serum were determined by ELISA kits. The levels of some gut microbiota in the faeces were measured by qPCR and faecal differential metabolites were analysed by <sup>1</sup>H NMR. The results indicate that CUMS can exacerbate UC symptoms in mice by exacerbating inflammation, and UC+CUMS can disrupt gut microbiota and fatty acid metabolism. Paroxetine can improve the mental state of mice, reduce serum MPO activity, but increase TNF-α and IL-1β levels in the colon. In addition, paroxetine also can restore the intestinal flora of mice and improve intestinal absorption and metabolic function of amino acids and short-chain fatty acids.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852137","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}
Kazi Mohammad Ali Zinnah, Ali Newaz Munna, Sang-Youel Park
Autophagy is a vital mechanism that eliminates large cytoplasmic components via lysosomal degradation to maintain cellular homeostasis. The role of autophagy in cancer treatment has been studied extensively. Autophagy primarily prevents tumour initiation by maintaining genomic stability and preventing cellular inflammation. However, autophagy also supports cancer cell survival and growth by providing essential nutrients for therapeutic resistance. Thus, autophagy has emerged as a promising strategy for overcoming resistance and enhancing anti-cancer therapy. Inhibiting autophagy significantly improves the sensitivity of lung, colorectal, breast, liver and prostate cancer cells to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). This review investigates the intricate interplay between autophagy modulation and TRAIL-based therapy, specifically focussing on comparing the efficacy of late-stage autophagy inhibition versus early-stage inhibition in overcoming cancer resistance. We expose the distinctive advantages of late-stage autophagy inhibition by exploring the mechanisms underlying autophagy's impact on TRAIL sensitivity. Current preclinical and clinical investigations are inspected, showing the potential of targeting late-stage autophagy for sensitizing resistant cancer cells to TRAIL-induced apoptosis. This review emphasizes the significance of optimizing autophagy modulation to enhance TRAIL-mediated therapy and overcome the challenge of treatment resistance in cancer. We offer insights and recommendations for guiding the development of potential therapeutic strategies aimed at overcoming the challenges posed by treatment-resistant cancers.
{"title":"Optimizing autophagy modulation for enhanced TRAIL-mediated therapy: Unveiling the superiority of late-stage inhibition over early-stage inhibition to overcome therapy resistance in cancer","authors":"Kazi Mohammad Ali Zinnah, Ali Newaz Munna, Sang-Youel Park","doi":"10.1111/bcpt.14110","DOIUrl":"10.1111/bcpt.14110","url":null,"abstract":"<p>Autophagy is a vital mechanism that eliminates large cytoplasmic components via lysosomal degradation to maintain cellular homeostasis. The role of autophagy in cancer treatment has been studied extensively. Autophagy primarily prevents tumour initiation by maintaining genomic stability and preventing cellular inflammation. However, autophagy also supports cancer cell survival and growth by providing essential nutrients for therapeutic resistance. Thus, autophagy has emerged as a promising strategy for overcoming resistance and enhancing anti-cancer therapy. Inhibiting autophagy significantly improves the sensitivity of lung, colorectal, breast, liver and prostate cancer cells to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). This review investigates the intricate interplay between autophagy modulation and TRAIL-based therapy, specifically focussing on comparing the efficacy of late-stage autophagy inhibition versus early-stage inhibition in overcoming cancer resistance. We expose the distinctive advantages of late-stage autophagy inhibition by exploring the mechanisms underlying autophagy's impact on TRAIL sensitivity. Current preclinical and clinical investigations are inspected, showing the potential of targeting late-stage autophagy for sensitizing resistant cancer cells to TRAIL-induced apoptosis. This review emphasizes the significance of optimizing autophagy modulation to enhance TRAIL-mediated therapy and overcome the challenge of treatment resistance in cancer. We offer insights and recommendations for guiding the development of potential therapeutic strategies aimed at overcoming the challenges posed by treatment-resistant cancers.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stine J. Gauger, Maria E. K. Lie, Ilse Wallaard, Yongsong Tian, Aleš Marek, Bente Frølund, Geeske M. van Woerden, Ype Elgersma, Birgitte R. Kornum, Petrine Wellendorph
Angelman Syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of ubiquitin-protein ligase E3A (UBE3A), resulting in marked changes in synaptic plasticity. In AS mice, a dysregulation of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) was previously described. This has been convincingly validated through genetic rescue of prominent phenotypes in mouse cross-breeding experiments. Selective ligands that specifically stabilize the CaMKIIα central association (hub) domain and affect different conformational states in vitro are now available. Two of these ligands, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and (E)-2-(5-hydroxy-2-phenyl-5,7,8,9-tetrahydro-6H-benzo[7]annulen-6-ylidene)acetic acid (Ph-HTBA), confer neuroprotection after ischemic stroke in mice where CaMKIIα is known to be dysregulated. Here, we sought to investigate whether pharmacological modulation with these prototypical CaMKIIα hub ligands presents a viable approach to alleviate AS symptoms. We performed an in vivo functional evaluation of AS mice treated for a total of 14 days with either HOCPCA or Ph-HTBA (7 days pre-treatment and 7 days of behavioural assessment). Both compounds were well-tolerated but unable to revert robust phenotypes of motor performance, anxiety, repetitive behaviour or seizures in AS mice. Biochemical experiments subsequently assessed CaMKIIα autophosphorylation in AS mouse brain tissue. Taken together our results indicate that pharmacological modulation of CaMKIIα via the selective hub ligands used here is not a viable treatment strategy in AS.
{"title":"CaMKIIα hub ligands are unable to reverse known phenotypes in Angelman syndrome mice","authors":"Stine J. Gauger, Maria E. K. Lie, Ilse Wallaard, Yongsong Tian, Aleš Marek, Bente Frølund, Geeske M. van Woerden, Ype Elgersma, Birgitte R. Kornum, Petrine Wellendorph","doi":"10.1111/bcpt.14112","DOIUrl":"10.1111/bcpt.14112","url":null,"abstract":"<p>Angelman Syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of ubiquitin-protein ligase E3A (UBE3A), resulting in marked changes in synaptic plasticity. In AS mice, a dysregulation of Ca<sup>2+</sup>/calmodulin-dependent protein kinase II alpha (CaMKIIα) was previously described. This has been convincingly validated through genetic rescue of prominent phenotypes in mouse cross-breeding experiments. Selective ligands that specifically stabilize the CaMKIIα central association (hub) domain and affect different conformational states in vitro are now available. Two of these ligands, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and (<i>E</i>)-2-(5-hydroxy-2-phenyl-5,7,8,9-tetrahydro-6<i>H</i>-benzo[7]annulen-6-ylidene)acetic acid (Ph-HTBA), confer neuroprotection after ischemic stroke in mice where CaMKIIα is known to be dysregulated. Here, we sought to investigate whether pharmacological modulation with these prototypical CaMKIIα hub ligands presents a viable approach to alleviate AS symptoms. We performed an in vivo functional evaluation of AS mice treated for a total of 14 days with either HOCPCA or Ph-HTBA (7 days pre-treatment and 7 days of behavioural assessment). Both compounds were well-tolerated but unable to revert robust phenotypes of motor performance, anxiety, repetitive behaviour or seizures in AS mice. Biochemical experiments subsequently assessed CaMKIIα autophosphorylation in AS mouse brain tissue. Taken together our results indicate that pharmacological modulation of CaMKIIα via the selective hub ligands used here is not a viable treatment strategy in AS.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817005","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}
Naeem Abdul Ghafoor, Sabina Rasuli, Özgür Tanriverdi, Ayşegül Yildiz
The MDM2-p53 pathway plays a pivotal role in regulating cell cycle and apoptosis, with its dysfunction contributing to approximately 50% of human malignancies. MDM2, an E3 ubiquitin ligase, targets the tumour suppressor p53 for degradation, thereby promoting uncontrolled cell growth in cancers. Inhibiting the MDM2-p53 interaction represents a promising therapeutic strategy for reactivating p53’s tumour-suppressive functions. This study explored the potential of ibutamoren (IBU) as a novel inhibitor of MDM2. In silico analyses utilizing molecular modelling revealed that IBU has a low IC50 for MDM2 inhibition and favourably binds to the p53-binding pocket of MDM2. In vitro experiments demonstrated that IBU treatment reduced the viability of immortalized cancer cell lines with a functional MDM2-p53 pathway but not in cell lines where this pathway harboured damaging mutations. This trend was further supported by RT-qPCR analysis, which showed differential expression of two p53 target genes upon IBU treatment in cell lines with wild MDM2-p53 pathways but not in those harbouring damaging mutations. These findings provide preliminary evidence supporting IBU's anticancer activity, plausibly through the MDM2-p53 pathway, and suggest that further studies are warranted to explore its mechanism of action and potential development as a lead compound in oncology research.
{"title":"Investigating the P53-dependent anti-cancer effect of ibutamoren in human cancer cell lines","authors":"Naeem Abdul Ghafoor, Sabina Rasuli, Özgür Tanriverdi, Ayşegül Yildiz","doi":"10.1111/bcpt.14111","DOIUrl":"10.1111/bcpt.14111","url":null,"abstract":"<p>The MDM2-p53 pathway plays a pivotal role in regulating cell cycle and apoptosis, with its dysfunction contributing to approximately 50% of human malignancies. MDM2, an E3 ubiquitin ligase, targets the tumour suppressor p53 for degradation, thereby promoting uncontrolled cell growth in cancers. Inhibiting the MDM2-p53 interaction represents a promising therapeutic strategy for reactivating p53’s tumour-suppressive functions. This study explored the potential of ibutamoren (IBU) as a novel inhibitor of MDM2. In silico analyses utilizing molecular modelling revealed that IBU has a low IC<sub>50</sub> for MDM2 inhibition and favourably binds to the p53-binding pocket of MDM2. In vitro experiments demonstrated that IBU treatment reduced the viability of immortalized cancer cell lines with a functional MDM2-p53 pathway but not in cell lines where this pathway harboured damaging mutations. This trend was further supported by RT-qPCR analysis, which showed differential expression of two p53 target genes upon IBU treatment in cell lines with wild MDM2-p53 pathways but not in those harbouring damaging mutations. These findings provide preliminary evidence supporting IBU's anticancer activity, plausibly through the MDM2-p53 pathway, and suggest that further studies are warranted to explore its mechanism of action and potential development as a lead compound in oncology research.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817006","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}
Natural products constitute a vast source of bioactive compounds with the potential of providing valuable insight for future medicines. However, from a pharmacological perspective, natural product studies are also often accompanied by serious limitations due to, for example, the complex nature of biological extracts, the challenge of reproducibly characterizing the extract and providing an exhaustive list of constituents and, consequently, the difficulties in linking the observed pharmacological effects to specific chemical entities. The present paper discusses the major challenges of studies with natural products and provides a guideline to be followed by authors submitting research findings involving data from natural products, and their derivatives, to Basic & Clinical Pharmacology & Toxicology.
{"title":"BCPT perspectives on studies involving natural products, traditional Chinese medicine and systems pharmacology","authors":"Pernille Tveden-Nyborg, Baoxue Yang, Ulf Simonsen, Jens Lykkesfeldt","doi":"10.1111/bcpt.14109","DOIUrl":"10.1111/bcpt.14109","url":null,"abstract":"<p>Natural products constitute a vast source of bioactive compounds with the potential of providing valuable insight for future medicines. However, from a pharmacological perspective, natural product studies are also often accompanied by serious limitations due to, for example, the complex nature of biological extracts, the challenge of reproducibly characterizing the extract and providing an exhaustive list of constituents and, consequently, the difficulties in linking the observed pharmacological effects to specific chemical entities. The present paper discusses the major challenges of studies with natural products and provides a guideline to be followed by authors submitting research findings involving data from natural products, and their derivatives, to Basic & Clinical Pharmacology & Toxicology.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"782-785"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daptomycin, an anti-methicillin-resistant Staphylococcus aureus drug, causes exposure-dependent muscle toxicity and eosinophilic pneumonia. Although the area under the concentration-time curve (AUC)-guided dosing is crucial, an optimal blood sampling strategy is lacking. This study aimed to identify an optimal limited sampling strategy using Bayesian forecasting to rapidly achieve the target AUC. Two validated population pharmacokinetic models generated a virtual population of 1000 individuals (models 1 and 2 represent diverse patients and kidney transplant recipients, respectively). The AUC for each blood sample was assessed using the probability of achieving the estimated/reference AUC ratio on the second day (AUC24–48) and at the steady state (AUCss). In Model 1, Bayesian posterior probabilities for AUC24–48 increased from 50.7% (a priori) to 59.4% and for AUCss from 48.9% (a priori) to 61.9%, with one-point Ctrough sampling at 24 h. With two-point sampling at 7 and 24 h, the probabilities increased to 73.8% for AUC24–48 and 69.7% for AUCss. In Model 2, the probabilities for both AUC24–48 and AUCss with one-point Ctrough or two-point sampling incorporating Ctrough sampling increased compared to a priori probabilities. These results suggest that two-point sampling incorporating Ctrough during initial dosing enhanced achieving the target AUC24–48 and AUCss rapidly.
{"title":"Limited sampling approach for model-informed precision dosing of daptomycin to rapidly achieving the target area under the concentration-time curve: A simulation study","authors":"Tomoyuki Yamada, Kazutaka Oda, Masami Nishihara, Akira Ashida","doi":"10.1111/bcpt.14108","DOIUrl":"10.1111/bcpt.14108","url":null,"abstract":"<p>Daptomycin, an anti-methicillin-resistant <i>Staphylococcus aureus</i> drug, causes exposure-dependent muscle toxicity and eosinophilic pneumonia. Although the area under the concentration-time curve (AUC)-guided dosing is crucial, an optimal blood sampling strategy is lacking. This study aimed to identify an optimal limited sampling strategy using Bayesian forecasting to rapidly achieve the target AUC. Two validated population pharmacokinetic models generated a virtual population of 1000 individuals (models 1 and 2 represent diverse patients and kidney transplant recipients, respectively). The AUC for each blood sample was assessed using the probability of achieving the estimated/reference AUC ratio on the second day (AUC<sub>24–48</sub>) and at the steady state (AUC<sub>ss</sub>). In Model 1, Bayesian posterior probabilities for AUC<sub>24–48</sub> increased from 50.7% (<i>a priori</i>) to 59.4% and for AUC<sub>ss</sub> from 48.9% (<i>a priori</i>) to 61.9%, with one-point C<sub>trough</sub> sampling at 24 h. With two-point sampling at 7 and 24 h, the probabilities increased to 73.8% for AUC<sub>24–48</sub> and 69.7% for AUC<sub>ss</sub>. In Model 2, the probabilities for both AUC<sub>24–48</sub> and AUC<sub>ss</sub> with one-point C<sub>trough</sub> or two-point sampling incorporating C<sub>trough</sub> sampling increased compared to <i>a priori</i> probabilities. These results suggest that two-point sampling incorporating C<sub>trough</sub> during initial dosing enhanced achieving the target AUC<sub>24–48</sub> and AUC<sub>ss</sub> rapidly.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuel Inshutiyimana, Michael Matiop Aleu, Mustaf Aden Abdinoor, Mariyah Murtaza Janoowalla, Norhayati Norhayati
Although diloxanide is a drug of choice for treating asymptomatic amoebiasis, its mechanism of action (MOA) remains unclear. This review aims to shed light on the current understanding of the effectiveness and MOA of diloxanide in treating amoebiasis . It involves analysis of articles, retrieved from PubMed, Google Scholar and EBSCOhost, on diloxanide and the treatment of Entamoeba histolytica infection. Diloxanide is used in an ester form, which allows its high luminal concentration and greater efficacy than metronidazole in the management of asymptomatic amoebiasis. The current understanding of the action of diloxanide is based on its structural similarity to chloramphenicol at dichloroacetamide group. It acts against protein synthesis in E. histolytica trophozoites, blocking their conversion to more virulent and invasive cyst forms. Furthermore, it has a parasite clearance rate of 81–96% and treats amoebic abscesses when combined with metronidazole and chloroquine. Nevertheless, it is associated with adverse events such as flatulence, anorexia, headache and urticaria. Diloxanide is efficacious against amoebiasis but there is a need to explore its structure–activity relationship.The study suggests future directions, including novel drug formulations, diagnostic improvements, and combination regimens to enhance treatment outcomes and mitigate relapse associated with the use of diloxanide.
{"title":"Diloxanide in amoebiasis management: Unravelling the mechanism of action and effectiveness","authors":"Samuel Inshutiyimana, Michael Matiop Aleu, Mustaf Aden Abdinoor, Mariyah Murtaza Janoowalla, Norhayati Norhayati","doi":"10.1111/bcpt.14106","DOIUrl":"10.1111/bcpt.14106","url":null,"abstract":"<p>Although diloxanide is a drug of choice for treating asymptomatic amoebiasis, its mechanism of action (MOA) remains unclear. This review aims to shed light on the current understanding of the effectiveness and MOA of diloxanide in treating amoebiasis . It involves analysis of articles, retrieved from PubMed, Google Scholar and EBSCOhost, on diloxanide and the treatment of <i>Entamoeba histolytica</i> infection. Diloxanide is used in an ester form, which allows its high luminal concentration and greater efficacy than metronidazole in the management of asymptomatic amoebiasis. The current understanding of the action of diloxanide is based on its structural similarity to chloramphenicol at dichloroacetamide group. It acts against protein synthesis in <i>E. histolytica</i> trophozoites, blocking their conversion to more virulent and invasive cyst forms. Furthermore, it has a parasite clearance rate of 81–96% and treats amoebic abscesses when combined with metronidazole and chloroquine. Nevertheless, it is associated with adverse events such as flatulence, anorexia, headache and urticaria. Diloxanide is efficacious against amoebiasis but there is a need to explore its structure–activity relationship.The study suggests future directions, including novel drug formulations, diagnostic improvements, and combination regimens to enhance treatment outcomes and mitigate relapse associated with the use of diloxanide.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}