Pharmacology最新文献

{"title":"Eleclazine Suppresses Ventricular Fibrillation in Failing Rabbit Hearts with Ischemia-Reperfusion Injury Undergoing Therapeutic Hypothermia.","authors":"Hui-Ling Lee, Po-Cheng Chang, Hung-Ta Wo, Hao-Tien Liu, Ming-Shien Wen, Chung-Chuan Chou","doi":"10.1159/000542292","DOIUrl":"10.1159/000542292","url":null,"abstract":"<p><strong>Introduction: </strong>Eleclazine is a highly selective late sodium current inhibitor, possibly effective in reducing ventricular fibrillation (VF) in heart failure (HF) with ischemia-reperfusion (IR) injury. The electrophysiological effects of eleclazine at therapeutic hypothermia (TH) are unknown. We investigated the effects of eleclazine in suppressing VF in failing rabbit hearts with IR injury undergoing TH.</p><p><strong>Method: </strong>HF was induced by right ventricular pacing. An IR model was created using coronary artery ligation for 60 min, followed by reperfusion for 30 min. Hearts were excised and Langendorff-perfused for optical mapping and electrophysiological studies. Electrophysiological studies were repeated after TH (33°C) for 30 min or eleclazine (1 μm) infusion for 20 min.</p><p><strong>Results: </strong>In failing IR-injured hearts, eleclazine reduced action potential duration (APD) dispersion and accelerated intracellular Ca2+ uptake to suppress arrhythmogenic alternans but also exacerbated rate-dependent conduction slowing, resulting in neutral effects on VF inducibility at normothermia. TH increased VF severity. Eleclazine after TH ameliorated TH-induced APD dispersion and further depressed conduction to reduce VF inducibility and severity. TH after eleclazine also slowed conduction to a greater extent to reduce VF inducibility and severity by extrastimulus pacing. In control IR-injured hearts, eleclazine increased VF severity by dynamic pacing at normothermia, which was counteracted by TH.</p><p><strong>Conclusions: </strong>Eleclazine does not prevent VF at normothermia but reduces VF inducibility and severity by extrastimulus pacing at TH in isolated failing hearts with regional IR injury.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"151-164"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522754","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}

{"title":"Nephroprotective Effects of Curcumin in Murine Models of Focal and Segmental Glomerulosclerosis.","authors":"Sufia Husain, Nervana Mustafa Kamal Bayoumy, Fatima Noor, Hanan Hagar, Sufia Husain","doi":"10.1159/000543293","DOIUrl":"10.1159/000543293","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to explore the reno-protective effect of curcumin in focal and segmental glomerulosclerosis (FSGS) in murine models, a common chronic glomerulopathy that leads to end-stage renal disease.</p><p><strong>Methods: </strong>Adult Wistar rats were used in this experiment. One group was treated with intravenous Adriamycin (ADR) injection to induce FSGS similar to that seen in humans and a second group was co-administered ADR and curcumin (ADR-CUR). Saline-treated rats served as controls. Renal injury was assessed by measuring the levels of serum creatinine, blood urea nitrogen (BUN), triglyceride, and urinary protein. The homogenates of renal cortex were used to estimate the renal content of the inflammatory marker tumor necrosis factor-a (TNF-a); oxidative stress marker malonaldehyde (MDA); and two antioxidants superoxide dismutase (SOD) and reduced glutathione (GSH). In addition, the rat kidneys were harvested by ends of week 8 and week 12 and examined for histological abnormalities.</p><p><strong>Results: </strong>The ADR-treated rats showed biochemical and histological evidence of FSGS, in the form of proteinuria, elevated serum creatinine, BUN, and triglycerides, elevated renal TNF-a and MDA, and segmental glomerulosclerosis. The ADR-CUR-treated rats showed significant correction of all these variables. Co-administration with curcumin resulted in improvement of the proteinuria, serum creatinine, BUN, and triglyceride. The renal tissue levels of antioxidants SOD and GSH increased and that of TNF-a and MDA decreased and the histology revealed reduction in the extent of segmental glomerulosclerosis. The FSGS-associated renal damage was notably antagonized by curcumin treatment.</p><p><strong>Conclusion: </strong>Our findings confirm the reno-protective effects of curcumin as a potential therapeutic agent in protection against the progression of FSGS and indicate that it is mitigated by inhibition of oxidant injury and inflammation and also by promotion of antioxidants. Curcumin ameliorated the ADR-induced FSGS in murine models. It may be a promising compound in the treatment of FSGS in human subjects. More human studies are needed to further elucidate its effects in FSGS.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"221-230"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953662","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}

{"title":"SGLT2 Inhibitors May Increase Creatinine Clearance: Data Mining Utilizing the FDA Adverse Event Report System Database and Pharmacokinetic Study with Rats.","authors":"Yuichi Uwai, Tomohiro Nabekura","doi":"10.1159/000546838","DOIUrl":"10.1159/000546838","url":null,"abstract":"<p><strong>Introduction: </strong>Augmented renal clearance is a condition in which creatinine clearance exceeds 130 mL/min/1.73 m2. The present study aimed to identify drugs that increase creatinine clearance.</p><p><strong>Methods: </strong>We initially investigated drugs associated with an upsurge in the reporting frequencies of \"creatinine renal clearance increased\" (CRCI) and \"glomerular filtration rate increased\" (GFRI) using the FDA Adverse Event Reporting System (FAERS) database. Effect of the drugs on renal clearance of creatinine and lithium was examined using rats.</p><p><strong>Results: </strong>The database contained 625 reports on CRCI and GFRI. Among the primary suspect drugs identified, empagliflozin had the highest number of reports (29), followed by canagliflozin (27), emtricitabine/tenofovir (21), and sacubitril/valsartan (21). Dapagliflozin had 16 reports. Reporting odds ratios (95% confidence intervals) for empagliflozin, canagliflozin, and dapagliflozin were 29.7 (20.5-43.1), 28.6 (19.5-42.1), and 19.7 (12.0-32.3), respectively. In rats infused with phlorizin, a typical inhibitor of sodium-glucose cotransporters (SGLTs), increases were observed in fractional glucose excretion, creatinine clearance, and the renal clearance of lithium. The plasma concentration of creatinine remained unchanged, while that of lithium decreased. Renal glucose excretion in rats-administered phlorizin correlated with creatinine clearance (r = 0.859).</p><p><strong>Conclusion: </strong>These results suggest that SGLT2 inhibitors may increase renal clearance of creatinine or drugs.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"301-308"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497881","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}

{"title":"Retraction Statement.","authors":"","doi":"10.1159/000544828","DOIUrl":"10.1159/000544828","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"191"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033405","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}

{"title":"Population Pharmacokinetic of Vancomycin Administered by Continuous Infusion in Critically Ill Patients.","authors":"Haifa Ben Romdhane, Jean Baptiste Woillard, Najah Ben Fadhel, Zohra Chadli, Amel Chaabane, Naceur Boughattas, Nadia Ben Fredj, Karim Aouam","doi":"10.1159/000539866","DOIUrl":"10.1159/000539866","url":null,"abstract":"<p><strong>Introduction: </strong>Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes.</p><p><strong>Objective: </strong>The objective of this study was to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions.</p><p><strong>Methods: </strong>The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance [Cr-Cl]) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset.</p><p><strong>Results: </strong>A one-compartment model (volume of distribution [Vd], elimination from compartment [Ke]) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke, respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed a negative correlation between CLv and the severity of the renal impairment. The internal validation of the final model showed that the plot of individual-predicted concentration versus observed concentration resulted in r2 = 0.86 in the final model. The external validation of the final model showed an acceptable predictive performance.</p><p><strong>Conclusion: </strong>We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the target range which is critical in optimizing the efficacy and safety of this antibiotic.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"65-76"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000564","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}

{"title":"Non-Coding RNA Networks in Pulmonary Arterial Hypertension.","authors":"Bing Chen, Yu Xia, Yanjiao Jiang, Zengxian Sun, Yanyan Zhang, Yun Liu","doi":"10.1159/000541060","DOIUrl":"10.1159/000541060","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary artery hypertension (PAH) is a severe cardiovascular disease marked by a persistent increase in pulmonary artery resistance and pressure, leading to right ventricular strain, hypertrophy, and eventually right heart failure and death. Despite numerous available targeted therapies, the clinical needs for treating PAH remain unmet. Current treatments primarily aim to dilate pulmonary vessels rather than reverse pulmonary vascular remodeling, failing to offer a fundamental solution for PAH. Therefore, developing new therapies for this condition is urgently required.</p><p><strong>Summary: </strong>Recent research has highlighted the crucial role of non-coding RNAs (ncRNAs) in the occurrence and development of PAH. NcRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs), are a class of transcripts that do not translate proteins but affect various diseases at different levels, including chromatin modification, transcription regulation, post-translational processes.</p><p><strong>Key message: </strong>The current study delves into recent advancements in understanding how lncRNAs, circRNAs, miRNAs, and piRNAs contribute to the pathogenesis of PAH. This review addresses the existing research challenges and explores the potential of ncRNAs as both biomarkers and therapeutic targets, suggesting that ncRNAs may serve as valuable indicators and treatment options for the disease.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"110-121"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352535","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}

{"title":"Combined Herbal Medicine (<i>Achyranthes bidentata</i>, <i>Gastrodia elata</i>, and <i>Chaenomeles sinensis</i>) Increases Anti-Inflammatory and Anti-Oxidative Effects in a Mouse Model of Amyotrophic Lateral Sclerosis.","authors":"Eun Jin Yang","doi":"10.1159/000547388","DOIUrl":"10.1159/000547388","url":null,"abstract":"<p><strong>Introduction: </strong>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of motor neurons, finally leading to death by respiratory failure. However, no effective drug is available for treating patients with ALS owing to the complex pathological mechanisms. Herbal medicines are globally known for the effects of their multiple bioactive components and lack of adverse effects. This study investigated the effects of a combined herbal medicine formulation containing Achyranthes bidentata Blume, Gastrodia elata Blume, and Chaenomeles sinensis Koehne extracts on motor function and to analyze the underlying biological mechanisms in the gastrocnemius and tibia anterior muscles and spinal cord of hSOD1G93A mice.</p><p><strong>Methods: </strong>Rotarod and footprint analyses were performed to examine motor function. The biological mechanisms were examined using Western blot and immunohistochemistry analyses of the muscles and spinal cord in hSOD1G93A mice.</p><p><strong>Results: </strong>Herbal medicine treatment improved motor function in hSOD1G93A mice by reducing the expression of inflammation-related proteins (glial fibrillary acidic protein and CD11b) and oxidative stress-related proteins (heme oxygenase 1 and ferritin) in the gastrocnemius and tibia anterior muscles and spinal cord. It also regulated autophagy in the muscles and spinal cord of hSOD1G93A mice.</p><p><strong>Conclusion: </strong>Collectively, these findings suggest that the herbal medicine formulation reported herein may facilitate management of diseases with complex pathological mechanisms, such as ALS, or those with unclear pathological mechanisms.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"333-346"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637860","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}

{"title":"UBE2K Facilitates Erlotinib Resistance and Induces Epithelial Mesenchymal Transition in Osteosarcoma Cancer Stem-Like Cells via Activating the mTOR Signaling.","authors":"Ping Yang, Tian Wang, Lian Zhang, Qi Liu, Dexing Wang, Ping Yang","doi":"10.1159/000545370","DOIUrl":"10.1159/000545370","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma (OS) is an aggressive bone tumor, and EGFR inhibitors are commonly used as targeted drugs for OS treatment. Herein, roles of ubiquitin-conjugating enzyme E2K (UBE2K) in EGFR inhibitor resistance of OS were studied.</p><p><strong>Methods: </strong>CD133+ MG63 and CD133+ U2OS cells were isolated using sorting flow cytometry and defined as osteosarcoma stem cells (OSCs)-MG63 and OSCs-U2OS, respectively. The stemness in MG63 and U2OS cells was evaluated by sphere formation assay. Cell activity, apoptosis, and migration were appraised using CCK-8 assay, TUNEL staining, and wound healing assay. Western blotting was used to detect the expression of related proteins.</p><p><strong>Results: </strong>OSCs-MG63 and OSCs-U2OS cells showed erlotinib resistant and high expression of UBE2K. Knocking down UBE2K reversed the erlotinib resistance, declined migration rate, and inhibited mitochondrial biogenesis in OSCs-MG63 and OSCs-U2OS cells. Silencing UBE2K inhibited the stemness in MG63 and U2OS cells, accompanied by reduced CD133+ cell proportion and restrained sphere formation ability. Silencing UBE2K repressed the mTOR/4EBP1/Cyclin D1/p21 signaling pathway in OSCs-MG63 and OSCs-U2OS cells. Furthermore, the influence of UBE2K silencing on the stemness of MG63 cells and the epithelial-mesenchymal transition (EMT) progression in OSCs-MG63 cells was partially abolished by MHY1485, an agonist of mTOR signaling.</p><p><strong>Conclusion: </strong>UBE2K facilitated the erlotinib resistance and induced EMT in OSCs via regulating the mTOR signaling.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"276-289"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754287","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}

{"title":"Additive Inhibition of HERG Channels Expressed in Xenopus Oocytes by Antipsychotic Drugs and Citrus Juice Flavonoid Naringenin.","authors":"Keun-Hang Susan Yang, Dmytro Isaev, Murat Oz","doi":"10.1159/000541005","DOIUrl":"10.1159/000541005","url":null,"abstract":"<p><strong>Introduction: </strong>Citrus juice has been shown to cause QT prolongation in electrocardiograms of healthy volunteers, and naringenin, a major flavonoid found in citrus juice, has been identified as the potent inhibitor of human ether-a-go-go-related gene (HERG) channels as the cause of QT prolongation. Inhibition of HERG channels and prolongation of QT interval by antipsychotic drugs such as haloperidol, chlorpromazine, and clozapine have also been shown. However, naringenin's effect on HERG channel function in conjunction with antipsychotic medications has not been investigated.</p><p><strong>Methods: </strong>In the present study, we evaluated the effect of combining naringenin with antipsychotics on the function of HERG channels expressed in Xenopus oocytes.</p><p><strong>Results: </strong>When 30 µ<sc>m</sc> naringenin was added to antipsychotic drugs (1 µ<sc>m</sc> haloperidol, 10 µ<sc>m</sc> chlorpromazine, or 10 µ<sc>m</sc> clozapine), significantly greater HERG inhibition was demonstrated, compared to the inhibition caused by antipsychotic drugs alone. Co-application studies also showed that the magnitudes of inhibitions caused by naringenin + antipsychotics were similar to that predicted by the allotopic interaction model, suggesting that naringenin and antipsychotics bind to the HERG channel at different sites.</p><p><strong>Conclusion: </strong>The results suggest that there is an additive interaction between antipsychotics and naringenin. Due to the potential for repolarization heterogeneity and a decrease in repolarization reserve, this additive HERG inhibition may increase the risk of arrhythmias.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"122-126"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352534","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}

{"title":"Retraction Statement.","authors":"","doi":"10.1159/000542299","DOIUrl":"10.1159/000542299","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"62"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605999","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}