BMC Pharmacology & Toxicology最新文献

{"title":"Real-world research on beta-blocker usage trends in China and safety exploration based on the FDA Adverse Event Reporting System (FAERS).","authors":"Yilong Yan, Wenshuo An, Shenghui Mei, Qiang Zhu, Cao Li, Li Yang, Zhigang Zhao, Jiping Huo","doi":"10.1186/s40360-024-00815-w","DOIUrl":"10.1186/s40360-024-00815-w","url":null,"abstract":"<p><strong>Background: </strong>Beta-blockers are widely used, with continuously updated clinical recommendations. However, their application faces challenges in personalized treatment and safety. The study aimed to investigate the frequency and patterns of prescribing beta-blockers in China and to explore potential adverse event risk signals associated with beta-blockers, providing reference for rational medication use in clinical settings.</p><p><strong>Methods: </strong>Prescription data for beta-blockers from January 2018 to June 2023 were extracted through the Hospital Prescription Analysis Collaborative Project in China to analyze clinical usage trends. While adverse drug reaction reports for beta-blockers were obtained from the FDA Adverse Event Reporting System (FAERS) database. The classification and standardization of adverse drug event (ADE) reports were based on the preferred terms (PT) and corresponding system organ classes (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA). Signal detection utilized a proportion imbalance method.</p><p><strong>Results: </strong>In clinical practice, metoprolol dominated beta-blocker prescriptions in China, accounting for 62.2%. Beta-blockers were primarily prescribed to the elderly (65.7%) and male patients (57.0%). However, off-label use of beta-blockers was relatively widespread. For instance, sotalol was prescribed for hypertension at 18.25%, while esmolol was used for angina and heart failure at rates of 12.94% and 14.98%, respectively. In addition, we identified newly discovered adverse reactions associated with beta-blockers, such as BRASH syndrome (metoprolol: n = 186, ROR = 391.285; carvedilol: n = 72, ROR = 256.459), acute kidney injury (bisoprolol: n = 247, ROR = 5.641), premature baby (labetalol: n = 110, ROR = 91.385), and sleep disorder (propranolol: n = 254, ROR = 10.98).</p><p><strong>Conclusions: </strong>Metoprolol led the beta-blocker market in China. Attention was warranted regarding the newly discovered adverse reactions, such as the risk of acute kidney injury with bisoprolol and the potential for BRASH syndrome with metoprolol and carvedilol.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"86"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug risks associated with sarcopenia: a real-world and GWAS study.","authors":"Zhaoliang Zhang, Liehui Yao","doi":"10.1186/s40360-024-00813-y","DOIUrl":"10.1186/s40360-024-00813-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Drug-induced sarcopenia has not received adequate attention. Meanwhile, there is growing recognition of the importance of effective pharmacovigilance in evaluating the benefits and risks of medications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;The primary aim of this study is to investigate the potential association between drug use and sarcopenia through an analysis of adverse event reports from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and to evaluate the genetic factors contributing to drug-induced sarcopenia using summary-data-based Mendelian randomization (SMR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We obtained reports of adverse drug reactions from FAERS. Primary outcomes included sarcopenia and potential sarcopenia. We calculated the Proportional reporting ratio (PRR) to assess the risk of specific adverse events associated with various drugs, applying chi-square tests for statistical significance. Additionally, we used SMR based on Genome-wide association study (GWAS) to evaluate the potential associations between drug target genes of some significant medications and sarcopenia outcomes. The outcome data for sarcopenia included metrics as hand grip strength and appendicular lean mass (ALM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 55 drugs were identified as inducing potential sarcopenia, and 3 drugs were identified as inducing sarcopenia. The top 5 drugs causing a potential risk of sarcopenia were levofloxacin (PRR = 9.96, χ&lt;sup&gt;2&lt;/sup&gt; = 1057), pregabalin (PRR = 7.20, χ&lt;sup&gt;2&lt;/sup&gt; = 1023), atorvastatin (PRR = 4.68, χ&lt;sup&gt;2&lt;/sup&gt; = 903), duloxetine (PRR = 4.76, χ&lt;sup&gt;2&lt;/sup&gt; = 527) and venlafaxine (PRR = 5.56, χ&lt;sup&gt;2&lt;/sup&gt; = 504), and the 3 drugs that had been proved to induced sarcopenia included metformin (PRR = 7.41, χ&lt;sup&gt;2&lt;/sup&gt; = 58), aspirin (PRR = 5.93, χ&lt;sup&gt;2&lt;/sup&gt; = 35), and acetaminophen (PRR = 4.73, χ&lt;sup&gt;2&lt;/sup&gt; = 25). We identified electron-transfer flavoprotein dehydrogenase (ETFDH) and protein Kinase AMP-Activated Non-Catalytic Subunit Beta 1 (PRKAB1) as the primary drug target genes for metformin, while Prostaglandin-endoperoxide Synthase 1 (PTGS1) and Prostaglandin-endoperoxide Synthase 2 (PTGS2) were considered the primary action target genes for aspirin and acetaminophen according to DrugBank database. SMR showed that the expression abundance of ETFDH was negatively correlated with right hand grip strength (blood: OR = 1.01, p-value = 1.27e-02; muscle: OR = 1.01, p-value = 1.42e-02) and negatively correlated with appendicular lean mass (blood: OR = 1.03, p-value = 7.73e-08; muscle: OR = 1.03, p-value = 1.67e-07).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We find that metformin, aspirin, and acetaminophen are specifically noted for their potential to induce sarcopenia based on the analyses conducted. We perform signal mining for drug-associated sarcopenia events based on real-world data and provides certain guidance for the safe use of medications to prevent sarcopenia","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"84"},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic profile of novel multi-layer stable effervescent tablet: a cross-over study with an established European brand in healthy young male adults.","authors":"Danish Hassan Dani, Syed Baqir Shyum Naqvi, Muhammad Akram, Matti Ullah, Sheikh Abdul Khaliq, Muhammad Masoom Akhtar, Orva Abdullah, Syed Faisal Badshah, Mohammed Bourhia, Gamal A Shazly, Yousef A Bin Jardan, Srosh Fazil","doi":"10.1186/s40360-024-00808-9","DOIUrl":"10.1186/s40360-024-00808-9","url":null,"abstract":"<p><p>Effervescent formulation helps in faster and better absorption of drugs, especially those that are rapidly soluble in water. However, these tablets require special packaging in order to prevent them from absorbing moisture, hence increasing cost. We compared an effervescent tablet prepared using an in-house developed method (multi-layer tablet with acid and base part separated by an inert layer) to a European effervescent tablet (Efferalgan®) in a single-center, randomized cross-over study among twelve healthy volunteers. Blood samples were collected for 8 h and analyzed for paracetamol concentration using HPLC. Our results showed that both the products have similar pharmacokinetic profiles with no significant difference observed for C_last, T_half, K_elim, and MRT (p-value > 0.05). Moreover, to assess bioequivalence we did not find any significant difference (p-value > 0.05) in AUC (27.12 ± 6.02 vs. 27.29 ± 2.64 µg.h/ml), C_max (7.42 ± 1.06 vs. 7.83 ± 1.19 µg/ml) and t_max (0.85 ± 0.22 vs. 0.83 ± 0.25 h). The TR ratios for AUC, C_max, and t_max were 0.99, 0.95, and 1.02 respectively, and were all within the specified FDA limits i.e., 0.8-1.25. We found our test tablet to be bioequivalent to that of Efferalgan®.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"83"},"PeriodicalIF":2.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective role of resveratrol in renal ischemia-reperfusion injury: a preclinical study in Sprague-Dawley rats.","authors":"Elaf R Alaasam, Ali M Janabi, Karrar M Al-Buthabhak, Rihab H Almudhafar, Najah R Hadi, Athanasios Alexiou, Marios Papadakis, Mohammed E Abo-El Fetoh, Dalia Fouad, Gaber El-Saber Batiha","doi":"10.1186/s40360-024-00809-8","DOIUrl":"10.1186/s40360-024-00809-8","url":null,"abstract":"<p><strong>Background: </strong>Renal ischemia-reperfusion injury (IRI) is a significant contributor to renal dysfunction, acute kidney injury (AKI), and associated morbidity and mortality. Resveratrol, a polyphenol and phytoalexin, is known for its anti-inflammatory, antioxidant, and anti-cancer properties. This study investigates the nephroprotective potential of resveratrol in a rat model of renal IRI.</p><p><strong>Materials and methods: </strong>Twenty-eight male Sprague-Dawley rats were divided into four groups: Sham, IRI, DMSO, and Resveratrol. The Sham group underwent identical procedures without renal pedicle clamping, while the IRI group experienced 30 min of ischemia followed by 2 h of reperfusion. The DMSO group received dimethyl sulfoxide (DMSO) intraperitoneally 30 min before ischemia, and the Resveratrol group received 30 mg/kg resveratrol intraperitoneally 30 min before ischemia. Biochemical parameters (Urea, creatinine, IL-1β, NF-κβ, SOD, GSH, Bcl-2, and caspase-3) and histopathological changes were assessed.</p><p><strong>Results: </strong>IRI caused a substantial increase in serum creatinine, Urea, IL-1β, NF-κβ, and caspase-3 levels, while simultaneously decreasing SOD, GSH, and Bcl-2 levels. Resveratrol treatment mitigated these effects by lowering inflammatory and apoptotic markers, enhancing antioxidant defenses, and improving histological outcomes.</p><p><strong>Conclusion: </strong>Resveratrol demonstrates significant nephroprotective effects in renal IRI, primarily through its antioxidant, anti-inflammatory, and anti-apoptotic properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"82"},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative opioid use in Norway-a population-based observational study on patterns of long-term use.","authors":"Sara Magelssen Vambheim, Vidar Hjellvik, Ingvild Odsbu, Svetlana Skurtveit, Christopher Ekholdt, Lars Petter Granan, Audun Stubhaug, Per-Jostein Samuelsen","doi":"10.1186/s40360-024-00805-y","DOIUrl":"10.1186/s40360-024-00805-y","url":null,"abstract":"<p><strong>Background: </strong>The utilization patterns of opioid analgesics and the proportion of long-term opioid use after surgery in Norway is largely unknown.</p><p><strong>Methods: </strong>This study aimed to estimate the proportion of one-year long-term prescription opioid use among all Norwegian postoperative opioid users. Complete data from central health registries (NPR, NorPD, Statistics Norway, CoDR) were linked via the personal identification number unique to all citizens. The study period was January 1st 2010 until December 31st 2019. Long-term opioid use was defined as at least two opioid dispensings within two subsequent 90-day periods, with a minimum average use of 10 MME/day for the first 90 days.</p><p><strong>Results: </strong>The study population consisted of 693 495 post-operative opioid users (53.6% women), whereof 73.2% had not used opioids the year before surgery (new users). Among the postoperative opioid users, 3.8% were one-year long-term opioid users. The corresponding figures for new and previous opioid users were 0.4% and 13.1%, respectively. The highest proportions of long-term opioid use were found after transluminal endoscopy, eye surgery and assessments related to surgical procedures. In previous opioid users, the proportion of one-year long-term use was higher among women than men in all age groups, a difference that increased with age.</p><p><strong>Conclusions: </strong>The proportion of postoperative long-term opioid use in Norway is generally low. We detected higher proportions of long-term opioid use after certain types of surgery, but our crude surgery definition warrants further examination. Previous opioid users pose a particular challenge in the management of postoperative pain.</p><p><strong>Trial registration: </strong>The study used national health registry data from the period 2010-2019. A pre-registered analysis plan is available at Open Science Framework.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"81"},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence study of eltrombopag 75 mg film-coated tablets under fasting conditions during the Covid-19 pandemic in healthy Caucasian male subjects.","authors":"Ahmet Inal, Zafer Sezer, Onur Pinarbasli, Burcu Bulut, Martin Reinsch, Wolfgang Martin, Mumtaz M Mazicioglu, Selma Alime Koru","doi":"10.1186/s40360-024-00803-0","DOIUrl":"10.1186/s40360-024-00803-0","url":null,"abstract":"<p><p>This study aims to determine the bioequivalence of the reference preparation and the test preparation containing eltrombopag when both were given during the COVID-19 pandemic while fasting. Participants in the research were healthy male Caucasian subjects. One film-coated tablet of the test preparation or one film tablet of the reference preparation, equivalent to 75 mg of eltrombopag, was given to the participants in a randomized order throughout each treatment session. At pre determined blood sampling points, blood samples were taken to determine the pharmacokinetics of eltrombopag. Eltrombopag concentrations in the samples were determined using an LC-MS/MS technique verified using ESI(-). The study results were used to calculate the rate (the maximum plasma concentration, or C_max) and extent (area under the concentration-time curve of plasma, or AUC_(0-72) and AUC_(0-t) of eltrombopag absorption from the test preparation and reference preparation. The 90% confidence intervals (CI) of the ln-transformed AUC_(0-72), AUC_(0-t), and C_max of eltrombopag met the bioequivalence requirements of 80.00-125.00%. Both trial preparations had a similar and very satisfactory safety profile.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"80"},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico molecular targets, docking, dynamics simulation and physiologically based pharmacokinetics modeling of oritavancin.","authors":"Toluwase Hezekiah Fatoki, Tosin Christianah Balogun, Adebayo Emmanuel Ojewuyi, Aduragbemi Christianah Omole, Oluwaseun Victor Olukayode, Afolasade Precious Adewumi, Adanne Joy Umesi, Nwadinma Priscillia Ijeoma, Abibat Esther Apooyin, Chinecherem Perpetual Chinedu, Ibukun Esther Idowu, Momoh Jimoh Isah","doi":"10.1186/s40360-024-00804-z","DOIUrl":"10.1186/s40360-024-00804-z","url":null,"abstract":"<p><strong>Introduction: </strong>Oritavancin is a semi-synthetic lipoglycopeptide antibiotic primarily used to treat serious infections caused by Gram-positive bacteria. The aim of this study was to elucidate possible molecular targets of oritavancin in human and microbes in relevance to its mechanism of action and model its pharmacokinetics for optimal dose selection in clinical practice.</p><p><strong>Methods: </strong>Computational methods were used in this study which include target prediction, molecular docking, molecular dynamics simulation, pharmacokinetics prediction, and physiological-based pharmacokinetics (PBPK) modeling.</p><p><strong>Results: </strong>Oritavancin was moderately soluble in water and did not permeate the blood-brain barrier. Seven molecular targets were identified in humans. Molecular docking results showed highest binding affinity of oritavancin with PI3-kinase p110-gamma subunit (-10.34 kcal/mol), followed by Acyl-CoA desaturase (-10.07 kcal/mol) and Cytochrome P450 2C19 (-8.384 kcal/mol). Oritavancin PBPK modelling in adult human showed that infusion has lower peak concentrations (Cmax) compared to bolus administration, with 1200 mg dose yielded Cmax of 16.559 mg/L, 800 mg dose yielded Cmax of 11.258 mg/L, and 200 mg over 3 days dose yielded Cmax of 7.526 mg/L. Notably, infusion gave extended half-life (t_1/2) for all doses and slightly higher clearance rates compared to bolus, particularly for the 1200 mg and 800 mg doses. The results corroborated existing clinical pharmacokinetic data, and confirmed the model's accuracy and predictive capability.</p><p><strong>Conclusion: </strong>This comprehensive computational study has provided invaluable insights into the pharmacological profile of Oritavancin, aiding its further development and optimization for clinical use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"79"},"PeriodicalIF":2.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Tenofovir Alafenamide Fumarate on the outcomes of hospitalized COVID-19 patients: a prospective, block-balanced, open-label, randomized controlled trial.","authors":"Nazanin Yazdan Pouri, Zahra Shokati Eshkiki, Afshin Talebi, Bahman Cheraghian, Fatemeh Ahmadi, Niloofar Neisi, Ali Akbar Shayesteh","doi":"10.1186/s40360-024-00781-3","DOIUrl":"10.1186/s40360-024-00781-3","url":null,"abstract":"<p><strong>Background: </strong>The global effort to cure COVID-19 is still ongoing. Thus, a prospective, block-balanced, open-label, randomized controlled trial was conducted to evaluate how Tenofovir Alafenamide Fumarate affects hospitalized COVID-19 patients' outcomes.</p><p><strong>Methods: </strong>The intervention and control groups of 60 hospitalized COVID-19 patients were randomly allocated. Along with normal medication, the intervention group received 25 mg of tenofovir orally daily for seven days. The control group got normal therapy, including remdesivir and corticosteroids. ICU hospitalization duration, laboratory data, fever, dyspnea, arterial blood oxygen saturation with and without an oxygen face mask, mechanical ventilation, and mortality were the outcomes.</p><p><strong>Results: </strong>Sixty of 236 eligible patients between September 2020 and February 2021 were enrolled. The intervention group had a mean age (±SD) of 61.33 (±13.09) years and the control group 60.03 (±18.03). Sixteen (53.3%) intervention patients and 15 (50.0%) control patients were males. The intervention group had fewer mechanical ventilation and ICU days. Tenofovir Alafenamide Fumarate did not improve fever, dyspnea, oxygen saturation with or without a face mask or nasal cannula, or laboratory data including WBC, ESR, CRP, AST, ALT, AlkP, total and direct bilirubin, in COVID-19 patients.</p><p><strong>Conclusion: </strong>According to this pilot trial, Tenofovir Alafenamide Fumarate, along with conventional treatment, significantly reduced mechanical ventilation and ICU stay in COVID-19 patients. Further thorough research is necessary to verify this conclusion.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"78"},"PeriodicalIF":2.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats.","authors":"Kamelia Saremi, Sima Kianpour Rad, Faezeh Tayeby, Mahmood A Abdulla, Hamed Karimian, Nazia Abdul Majid","doi":"10.1186/s40360-024-00801-2","DOIUrl":"https://doi.org/10.1186/s40360-024-00801-2","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"77"},"PeriodicalIF":2.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GR113808, a serotonin receptor 4 antagonist, prevents high-fat-diet-induced obesity, fatty liver formation, and insulin resistance in C57BL/6J mice.","authors":"Min Hee Kim, Su-Jeong Kim, Woo-Jae Park, Dae Ho Lee, Kyoung-Kon Kim","doi":"10.1186/s40360-024-00800-3","DOIUrl":"10.1186/s40360-024-00800-3","url":null,"abstract":"<p><strong>Background: </strong>The burden of nonalcoholic fatty liver disease is increasing, and limited therapeutic drugs are available for its treatment. Serotonin binds to approximately 14 serotonin receptors (HTR) and plays diverse roles in obesity and metabolic complications. In this study, we focused on the function of HTR4 on nonalcoholic fatty liver disease using GR113808, a selective HTR4 antagonist.</p><p><strong>Methods: </strong>Male C57BL/6J mice were fed high-fat diet for 12 weeks with intraperitoneal GR113808 injection, and HTR expression, weight changes, glucose and lipid metabolism, hepatic fat accumulation, changes in adipose tissue, the changes in transcriptional factors of signaling pathways, and inflammations were assessed. Hep3B cells and 3T3-L1 cells were treated with siRNA targeting HTR4 to downregulate its expression and then cultured with palmitate to mimic a high-fat diet. The changes in transcriptional factors of signaling pathways, and inflammations were assessed in those cells.</p><p><strong>Results: </strong>After feeding a high-fat diet to male C57BL/6J mice, HTR4 expression in the liver and adipose tissues decreased. GR113808 suppressed body weight gain and improved glucose intolerance. Furthermore, GR113808 not only decreased fatty liver formation but also reduced adipose tissue size. Additionally, GR113808 reduced inflammatory cytokine serum levels and inflammasome complex formation in both tissues. Palmitate treatment in HTR4-downregulated Hep3B cells, also reduced peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein-1 pathway induction as well as inflammasome complex formation, thus decreasing inflammatory cytokine levels. HTR4 downregulation in 3T3-L1 cells also reduced palmitate-induced inflammasome complex formation and inflammatory cytokine production. Palmitate-induced insulin resistance in Hep3B cells, but not in 3T3-L1 cells, was improved by HTR4 downregulation.</p><p><strong>Conclusions: </strong>In summary, GR113808 protected against fatty liver formation and improved inflammation in the liver and adipose tissue. Downregulation of HTR4 ameliorated insulin resistance in the liver. These results suggest that HTR4 could serve as a promising therapeutic target for metabolic diseases.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"76"},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}