Pharmacological Research - Reports最新文献

{"title":"The synthetic peptide, PnPP-15, derived from the PnTx2-6 toxin of the spider Phoneutria nigriventer, induces peripheral antinociception involving neprilysin, opioid, and cannabinoid systems","authors":"Renata Cristina Mendes Ferreira ,&nbsp;Edleusa Marques Lima-Batista ,&nbsp;Ana Cristina Nogueira Freitas ,&nbsp;Xavier Maia Mariano ,&nbsp;Marcelo Ferreira Marcondes Machado ,&nbsp;Dongchen Na ,&nbsp;Adriana Karaoglanovic Carmona ,&nbsp;Steve Peigneur ,&nbsp;William Gustavo Lima ,&nbsp;Brener Cunha Carvalho ,&nbsp;Carlos Alberto Tagliati ,&nbsp;Jan Tytgat ,&nbsp;Igor Dimitri Gama Duarte ,&nbsp;Maria Elena de Lima","doi":"10.1016/j.prerep.2024.100012","DOIUrl":"https://doi.org/10.1016/j.prerep.2024.100012","url":null,"abstract":"<div><h3>Background</h3><p>The PnTx2–6 toxin is isolated from the Phoneutria nigriventer spider venom. The synthetic peptide PnPP-19 is derived from this toxin and induces antinociception. When topically applied, it is cleaved by proteases generating a 15 amino acid residues peptide, PnPP-15. PnPP-15 showed an antinociceptive effect in neuropathic pain developed by streptozotocin-induced diabetic mice. The present work aimed to investigate if PnPP-15 is also effective against the inflammatory pain induced by PGE₂. We also evaluated its cytotoxicity <em>in vitro</em> and studied its possible action mechanism in the pain pathway.</p></div><div><h3>Methods</h3><p>The nociceptive threshold was assessed using the mechanical paw pressure test. Paw tissue was collected for protein extraction and western blot analyses. The FRET enzymatic assay measured neprilysin activity. The two-electrode voltage clamp technique measured evoked electrical currents in <em>Xenopus laevis</em> oocytes. Cytotoxicity was measured using multiple cell lines.</p></div><div><h3>Results</h3><p>PnPP-15 has peripheral antinociceptive activity <em>via</em> µ-opioid and CB₁ cannabinoid receptors and inhibits neprilysin. In addition, it induced direct activation of mu-opioid receptors expressed in <em>Xenopus laevis</em> oocytes. PnPP-15 was not cytotoxic against mammalian kidney, liver, heart, nerve, or lung cells.</p></div><div><h3>Conclusion</h3><p>This work demonstrated the antinociceptive effect of PnPP-15 in an inflammatory pain model, suggesting its use as a possible tool for developing new analgesic drugs.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000120/pdfft?md5=894719be290c29f9baee9c6b92b49796&pid=1-s2.0-S2950200424000120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141484179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reno-protective effect of Roflumilast against kidney injury induced by ischemia/reperfusion in rats: Evidence from biochemical and histological investigations","authors":"Rehab F. Abdel-Rahman ,&nbsp;Marawan A. Elbaset ,&nbsp;Hany M. Fayed ,&nbsp;Tuba Esatbeyoglu ,&nbsp;Sherif M. Afifi ,&nbsp;Rehab Adel Diab","doi":"10.1016/j.prerep.2024.100014","DOIUrl":"10.1016/j.prerep.2024.100014","url":null,"abstract":"<div><p>Oxidative stress, inflammation, and apoptosis are major contributors to renal ischemia/reperfusion (I/R) injury. This study aimed to investigate the effects of pretreatment with the PDE4 inhibitor roflumilast (Rof) on renal I/R and its underlying mechanisms. Sprague-Dawley rats were subjected to 30 minutes of unilateral renal ischemia followed by 45 minutes of reperfusion. Rof (1.5 and 3 mg/kg) was administered for seven days prior to I/R induction. The findings showed that Rof significantly and dose-dependently attenuated kidney damage by reducing blood urea nitrogen and creatinine levels. Rof also exhibited antioxidant and anti-inflammatory effects, as evidenced by improved glutathione and malondialdehyde levels and decreased proinflammatory cytokines (IL-6 and TNF-α). Furthermore, Rof prevented the downregulation of HO-1 and Nrf2 expression. These results suggest that Rof therapy could protect the kidneys from I/R-induced injury through its antioxidant and anti-inflammatory properties, providing a potential therapeutic approach for the management of renal I/R damage.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000144/pdfft?md5=a3f31ca1c43526d3422212ed0c38e78f&pid=1-s2.0-S2950200424000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mirabegron alleviates fructose induced nonalcoholic fatty liver disease in rats: Insights into the underlying mechanisms","authors":"Chandaka Madhavarao ,&nbsp;Masa Amala ,&nbsp;Grandhi Sandeep Ganesh","doi":"10.1016/j.prerep.2024.100018","DOIUrl":"10.1016/j.prerep.2024.100018","url":null,"abstract":"<div><h3>Aim</h3><p>Non-alcoholic fatty liver disease (NAFLD) is one of the progressive and chronic disease encompass a range of conditions such as non-alcoholic steatohepatitis (NASH) and cirrhosis. The present study is aimed to elucidate the possible actions of mirabegron, a β3-adrenoreceptor agonist used in the treatment of over active bladder, against NAFLD induced by fructose.</p></div><div><h3>Method</h3><p>30 male Wistar rats were randomized into 5 groups (A) Veh, (B) Fru, (C) Fru + Sita, (D) Fru + Mira and (E) Fru + Mira + Resv. Rats of respective groups were treated with mirabegron (10 mg/kg, p.o.), sitagliptin (10 mg/kg, p.o.) and resveratrol (20 mg/kg, p.o.) daily for 14 days. Fructose water was given to all rats to induce NAFLD till end of the study. Simultaneously, biochemical analysis such as glucose, SGOT, SGPT, HDL, LDL, TC and TG were performed to assess the disease progression. In the end of study hepatic biochemistry, SOD, MDA, GSH, inflammatory markers such as TNF-α, IL-1β and Hematoxylin and Eosin (H&amp;E) analysis were performed.</p></div><div><h3>Key findings</h3><p>The NAFLD rats exhibited a significant weight gain, substantial increase in liver enzymes, glucose, circulating and hepatic total cholesterol, triglycerides, inflammatory cytokines and histological analysis showed hepatic steatosis and inflammation in the Fru group. In contrast, mirabegron alone and in combination with antioxidant provided a promising data on ameliorative effect on hepatic inflammation and steatosis caused by fructose. As a result, mirabegron is found to be a promising therapeutic treatment strategy for NAFLD and its associated complications.</p></div><div><h3>Significance</h3><p>Collectively, findings in this present study revealed that mirabegron reversed NAFLD by suppressing fructose mediated inflammation, oxidative stress and steatosis.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000181/pdfft?md5=c7adf0763458b6d5f27a71bcab129149&pid=1-s2.0-S2950200424000181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142149550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in mesenchymal stem cell therapy and natural antioxidants for hepatic fibrosis: A comprehensive review","authors":"Abeer Kazmi ,&nbsp;Tahira Sultana","doi":"10.1016/j.prerep.2024.100016","DOIUrl":"10.1016/j.prerep.2024.100016","url":null,"abstract":"<div><p>Liver damage resulting from the administration of various allopathic drugs and their associated toxicity has become a major health problem, leading to hepatic fibrosis, cirrhosis, and metabolic disorders. This epidemic condition of liver disease represents a major global cause of death and morbidity. Although orthotopic liver transplantation remains a vital treatment option for fibrotic liver conditions, its efficacy is limited by organ scarcity and the risk of immunological rejection. Consequently, alternative therapeutic approaches are urgently needed. Cell-based therapy utilizing mesenchymal stem cells (MSCs) has garnered considerable interest as a promising treatment modality. MSCs exhibit immunomodulatory properties and can differentiate into hepatocytes, thus facilitating the regeneration of damaged hepatocytes and increasing residual hepatocyte proliferation while inhibiting activation or apoptosis of liver stellate cells. However, despite their potential benefits, transplanted cells often exhibit low survival rates due to inadequate oxidative and inflammatory stress resistance. Plants harbor a diverse array of bioactive compounds known to possess hepatoprotective and antioxidant properties. Nanomaterials play a crucial role in regenerative medicine by providing targeted delivery of therapeutic agents and scaffolds for tissue engineering. In treating fibrotic liver, nanomaterials can help mitigate fibrosis progression and promote liver regeneration through controlled release of anti-fibrotic agents and growth factors. This review highlights the synergistic potential of stem cell-based therapy, natural antioxidants, differentiation factors, and nanotechnology in combating hepatic fibrosis and advancing liver regenerative medicine. These combined approaches offer promising avenues for effectively treating fibrotic liver conditions and promoting tissue regeneration.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000168/pdfft?md5=56f9f80a84bc75af31ab28a7294941c3&pid=1-s2.0-S2950200424000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bongkrekic acid inhibits 2-deoxygulcose-induced apoptosis, leading to enhanced cytotoxicity and necrotic cell death","authors":"Arihiro Kano ,&nbsp;Miho Fujiki ,&nbsp;Keiya Fukami ,&nbsp;Mitsuru Shindo ,&nbsp;Jeong-Hun Kang","doi":"10.1016/j.prerep.2024.100017","DOIUrl":"10.1016/j.prerep.2024.100017","url":null,"abstract":"<div><p>Targeting glucose metabolism using the glycolysis inhibitor, 2-deoxyglucose (2-DG), is a promising therapeutic strategy for cancers characterized by elevated glucose requirements. Although clinical studies have revealed that effective doses cause side effects, research on combination therapies is ongoing. 2-DG inhibits not only glycolysis but also glycosylation of newly synthesized proteins and disturbs protein folding, resulting in endoplasmic reticulum (ER) stress-mediated apoptosis. Meanwhile, bongkrekic acid (BKA) is a toxic compound, which has been reported to inhibit ADP/ATP exchange in the mitochondria and suppress apoptosis by interfering with cytochrome <em>c</em> release from the mitochondria. Herein, 100 µM BKA inhibited 2-DG-induced apoptosis but showed enhanced cytotoxicity in the 4T1 murine breast cancer cell line, resulting in necrotic cell death. Surprisingly, BKA did not suppress 2-DG-induced cytochrome <em>c</em> release from the mitochondria, but effectively inhibited caspase activation. Furthermore, BKA did not suppress the upregulation of ER stress marker C/EBP homologous protein but suppressed autophagy flux. Our findings suggest an alternative treatment for cancer using BKA in combination with 2-DG.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S295020042400017X/pdfft?md5=6233f23e686d434fe534ea56eacfdc67&pid=1-s2.0-S295020042400017X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142149549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of chronic plaque psoriasis: An overview on current update","authors":"Priyanka Jurel,&nbsp;Shiv Bahadur,&nbsp;Meenakshi Bajpai","doi":"10.1016/j.prerep.2024.100004","DOIUrl":"10.1016/j.prerep.2024.100004","url":null,"abstract":"<div><h3>Introduction</h3><p>Chronic plaque psoriasis is an inflammatory skin disorder that affects 2–3% of the population. The severity of the disease is influenced by the number and location of skin lesions, concomitant conditions such psoriatic arthritis, and the impact on daily life. Several comorbidities, such as depression, cardiometabolic disorders, and psoriatic arthritis, are linked to plaque psoriasis. Hence, aim of current review is to highlight the comprehensive information on the pathophysiology, mechanism of action of recent approved drugs and future prospective. Further, clinical research and lengthy prospective cohort studies have been discussed.</p></div><div><h3>Materials and methods</h3><p>The data were collected from the various reported literatures PubChem, scopus and other search engines which are suggesting for the management of plaque psoriasis. These literature review were selected based on the current updated treatment of chronic plaque psoriasis.</p></div><div><h3>Result</h3><p>Various biologics have been promoted by the National Psoriasis Foundation guidelines as a first-line treatment option for moderate to severe plaque psoriasis due to their effectiveness in treating the condition and their acceptable safety profiles. The aryl hydrocarbon receptor (AhR) modulator tapinarof, the phosphodiesterase-4 (PDE4) inhibitor roflumilast and the tyrosine kinase 2 (TYK2) inhibitor deucravacitinib are the new drugs approved by US Food and Drug Administration (FDA) for promising treatment mild-severe plaque psoriasis.</p></div><div><h3>Discussions</h3><p>The conventional systemic therapy for treatment of plaque psoriasis was found to be unsatisfactory due to several significant adverse effects and contraindications. It is vital to continue developing efficacious, safe, and tolerant systemic medication approach capable of being employed as first-line systemic treatments for those with moderate-to-severe psoriasis. The recent approved drugs by USFDA for the management of psoriasis offer the potential for enhanced efficacy and better disease control.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000041/pdfft?md5=d24caf82979e1f1dd5cde9a96f162fa6&pid=1-s2.0-S2950200424000041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of the Rumsfeld matrix to anticancer natural product target discovery","authors":"Christian Bailly","doi":"10.1016/j.prerep.2024.100023","DOIUrl":"10.1016/j.prerep.2024.100023","url":null,"abstract":"<div><div>For a long time, natural products (NP) contribute to the treatment of human pathologies, notably to cancer treatment with microbial and plant-derived products. The mechanism of action of new NP can be investigated using computational methods, boosted by artificial intelligence-assisted procedures, to guide target discovery. But there remain many bioactive NP with unknown targets and/or an incompletely understood or opaque mechanism of action. The most innovative compounds are those with a previously unknown chemical scaffold associated to an unknown mechanism of action, despite evidence of bioactivities in pharmacological assays. This challenging “unknown unknown” category of compounds requires major efforts to elucidate their mechanism of action, with the possibility to identify unprecedented first-in-class approaches to treat advanced cancers. There are also chemically well-known NP for which novel properties and medicinal applications are revealed without an associated target. Such compounds belong to the “known unknown” group, as it is the case for the anticancer drug etoposide and its potent anti-inflammatory action exploited to treat lymphohistiocytosis. The situation is different with new scaffolds for which a potential mechanism or molecular target can be predicted on the basis of functional analogies with other molecules. The “known unknown” and “unknown known” products can be classified using a Rumsfeld ignorance matrix by categorizing them into four subgroups. A Johari window-type classification of NP and associated targets is proposed. The matrix can help compound management and identification of research gaps to generate insights for further study. The review retraces a scientific excursion into the unknown of NP pharmacology.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100023"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenebrio molitor as a new alternative model for the investigation of chemotherapy-induced intestinal toxicity","authors":"Lara Luisa Valerio de Mello Braga ,&nbsp;Gisele Simão ,&nbsp;Carolina Silva Schiebel ,&nbsp;Yasmin Felipichuki Oliveira ,&nbsp;Liza Brandão da Rosa ,&nbsp;Marcelo Biondaro Gois ,&nbsp;Elizabeth Soares Fernandes ,&nbsp;Daniele Maria-Ferreira","doi":"10.1016/j.prerep.2024.100013","DOIUrl":"10.1016/j.prerep.2024.100013","url":null,"abstract":"<div><p>Alternative animal models have become increasingly necessary due to legal regulations aimed at reducing the use of laboratory animals. Invertebrates are gaining in importance and have been intensively researched in recent years due to their pathophysiological similarities with rodents. Among these organisms, <em>Tenebrio molitor</em>, also known as the yellow mealworm beetle, stands out. In this study, we investigated whether <em>T. molitor</em> could be an alternative for studying the toxicity of chemotherapeutic agents. For this purpose, <em>T. molitor</em> larvae were inoculated with irinotecan (IRI) or 5-fluorouracil (5-FU). Both chemotherapeutic agents increased the morbidity and mortality of <em>T. molitor</em> and led to an increase in total circulating cells. Glucose levels were decreased after treatment with 5-FU and alanine aminotransferase levels were decreased after IRI administration. Administration of IRI or 5-FU resulted in changes in the appearance, consistency and amount of T. molitor frass. Finally, both IRI and 5-FU promoted severe histologic damage in the midgut and increased melanin deposition in peripheral tissues. Finally, we succeeded in developing an alternative experimental model for evaluating the toxicity of IRI and 5-FU. This model exhibits significant features of toxicity and intestinal damage, making it suitable for translational research purposes. <em>T. molitor</em> proves to be a versatile model organism with numerous advantages for experimental studies and offers a viable alternative for acquiring and expanding knowledge in the field of toxicology and pharmacology.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000132/pdfft?md5=c542c740d2a16d2352324ad8fa204d09&pid=1-s2.0-S2950200424000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141711022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diacerein reduces sensorimotor deficits after spinal cord injury by clip-compression in female rats by protection of cellular damage in long time","authors":"Fernando da Silva Fiorin ,&nbsp;Douglas Buchmann Godinho ,&nbsp;Rafael Parcianello Cipolat ,&nbsp;Luiz Fernando Freire Royes ,&nbsp;Caroline Cunha do Espírito Santo","doi":"10.1016/j.prerep.2024.100015","DOIUrl":"10.1016/j.prerep.2024.100015","url":null,"abstract":"<div><p>Spinal cord injury (SCI) is a cause of long-term disability, and one of the main problems is sensorimotor response impairment. Thus, become important treatments that reduce the progressive secondary damage that causes the loss of spared neurons. Due to the oxidative stress and inflammation interaction after damage, we tested if diacerein, a classic pharmacologic anti-inflammatory, could reduce the cell damage in the long term and recover sensorimotor responses after SCI in rats. Clip-compression SCI model in female Wistar rats caused severe locomotory loss performance showed through assessment by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and induced thermal hyperalgesia observed by Plantar Test Apparatus. When diacerein was administered twice a day for thirty-five days, the data presented a significant recovery of locomotion and an attenuation of thermal hyperalgesia. The increased adrenal glands’ weight and reduced soleus muscle mass were attenuated by diacerein. The immunoblotting showed that diacerein prevented progressive damage at the site of injury demonstrated by the recovery of nuclear factor erythroid-2 related factor 2 (Nrf2) levels, reduction of protein nitration by 3-nitrotyrosine (3-NT) expression and inflammation decreased showed by a less expression in glial fibrillary acidic protein (GFAP) immune content induced by injury. Therefore, the present data suggest that blockage of secondary damage by diacerein can inhibit the oxidative/inflammatory process by increasing Nrf2 and improving sensorimotor recovery in rats.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000156/pdfft?md5=422266203990cb7120bc4cd73df23797&pid=1-s2.0-S2950200424000156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fosfomycin mitigated apoptosis while increased mucin secretion in swine intestinal explants challenged by Lawsonia intracellularis","authors":"D.S.Pérez Gaudio ,&nbsp;C. Fodor ,&nbsp;J.M. Decundo ,&nbsp;G. Martínez ,&nbsp;J. Mozo ,&nbsp;V. Eguía ,&nbsp;S.N. Dieguez ,&nbsp;A.L. Soraci ,&nbsp;E.R. Cobo","doi":"10.1016/j.prerep.2024.100009","DOIUrl":"10.1016/j.prerep.2024.100009","url":null,"abstract":"<div><p>Lesions induced by the obligate intracellular bacterium <em>Lawsonia intracellularis</em>, the etiological agent of porcine proliferative enteropathy, are characterized by crypt hyperplasia in the intestinal epithelium with minimal inflammatory infiltration. An increased population of immature enterocytes at the expense of reduced goblet cells suggests that dysregulated apoptosis may be crucial in the pathogenesis of <em>L. intracellularis</em>.</p><p>Fosfomycin, a widely employed antibiotic in swine production, has also exhibited non-microbicidal effects, encompassing immunomodulation, augmentation of phagocytosis, and the promotion of cell survival. In this study, we assessed the immunomodulatory impact of fosfomycin on intestinal epithelial homeostasis using porcine intestinal explants challenged with <em>L. intracellularis</em>.</p><p>Our findings reveal that <em>L. intracellularis</em> elicited significant nuclear alterations, increased apoptotic indices, and prompted extensive mucin secretion in the intestinal explants. When fosfomycin was added to <em>L. intracellularis</em>-challenged intestinal explants, it mitigated the degree of apoptosis but also induced an inflammatory response. Consequently, treatment with fosfomycin in the context of <em>L. intracellularis</em> challenge appears to initiate an early mucosal response, maintaining cell viability, preserving the mucin barrier, and fostering inflammatory recruitment.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000090/pdfft?md5=67944480687976e5019a36b6537e20f8&pid=1-s2.0-S2950200424000090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}