Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Pharmaceutical-Related Poisonings in Greenland","authors":"Kim Dalhoff,&nbsp;Johanne Mølby Hansen,&nbsp;Søren Bøgevig,&nbsp;Tonny S. Petersen","doi":"10.1111/bcpt.70016","DOIUrl":"https://doi.org/10.1111/bcpt.70016","url":null,"abstract":"<p>The Danish Poison Information Centre (DPIC) received 1827 enquiries from Greenland in the period 2007–2022. The risk and the treatment of poisonings in Greenland are potentially different from those in Denmark. The use and availability of medicines, the ethnicity and the vicinity of health care are different in Greenland compared with Denmark. This study examined whether the toxicological profile was different between Denmark and Greenland using DPIC data. The most frequent drug poisoning in Greenland was paracetamol, followed by ibuprofen and quetiapine (6.6, 4.5 and 1.6 enquiries/1000 inhabitants, respectively). There were significantly more serious poisonings in Greenland compared with Denmark (36% vs. 12% moderate or life-threatening poisonings; <i>p</i> = 0.0004). Most of the calls from Greenland to the DPIC came primarily from health care professionals (HCPs). Also, the age groups of the poisoned patients were different in Greenland compared with Denmark. In Denmark, 38% of the enquiries were regarding children aged 0–4, compared with 17% in Greenland. In the age group 20–29 years, 14% came from Denmark and 23% from Greenland. In conclusion, we found an excessive number of calls to the DPIC from HCPs in Greenland with more serious poisonings, primarily with paracetamol, and fewer calls regarding children.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564999","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":"Cannabinol Interactions With the Melatonergic Pathway","authors":"George Anderson","doi":"10.1111/bcpt.70014","DOIUrl":"https://doi.org/10.1111/bcpt.70014","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533335","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":"Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity","authors":"Akimasa Sanagawa,&nbsp;Hiroshi Takase","doi":"10.1111/bcpt.70015","DOIUrl":"https://doi.org/10.1111/bcpt.70015","url":null,"abstract":"<p>Vemurafenib (VEM) reportedly inhibits the mitochondrial respiratory chain and reduces ferrochelatase (FECH) activity, thereby causing VEM-induced renal tubular toxicity. However, the exact mechanisms underlying VEM-induced renal tubular toxicity remain unclear. In this study, we treated human renal proximal tubular epithelial cells with VEM to elucidate these mechanisms. VEM treatment for 24 h resulted in cell damage, reduced cell viability, increased lactate dehydrogenase release and elevated the production of inflammatory cytokines. Transmission electron microscopy (TEM) and fluorescence microscopy revealed accumulation and enlargement of lysosome-derived vacuoles and mitochondrial superoxide production. Although MitoTracker showed no change in the total mitochondrial volume, TEM indicated mitochondrial damage, including smaller and less visible mitochondria. Enhanced superoxide production was confirmed using mtSOX. The mitochondria-specific antioxidant XJB-5-131 partially alleviated VEM-induced superoxide production and improved cell viability, indicating the role of superoxide in VEM-induced renal tubular toxicity. The inhibition of lysosomal acidification by bafilomycin A1 did not mitigate VEM-induced cytotoxicity, suggesting potential autophagy impairment. These findings highlight that mitochondrial dysfunction and lysosomal abnormalities are significant factors in VEM-induced renal tubular toxicity, warranting further investigation into the relationship between their mechanisms, reduced FECH activity and potential renoprotective targets.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513818","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":"Association Between CYP2D6 Genotypes and Serum Concentrations of Mirtazapine and Mianserin","authors":"Kristine Hole,&nbsp;Espen Molden","doi":"10.1111/bcpt.70013","DOIUrl":"https://doi.org/10.1111/bcpt.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of the present study was to investigate the effect of <i>CYP2D6</i> genotypes on mirtazapine and mianserin serum concentrations. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of <i>CYP2D6</i> genotype, age and sex on mirtazapine and mianserin concentration-to-dose (C/D) ratio. The study included 2315 mirtazapine patients and 474 mianserin patients who were assigned to the genotype-predicted phenotype groups of CYP2D6 poor metabolizers (PMs), intermediate metabolizers (IMs), normal metabolizers (NMs) and ultrarapid metabolizers (UMs). Multiple linear regression analysis revealed 18% and 14% higher mirtazapine C/D ratio in CYP2D6 PMs and IMs, respectively, compared with NMs (<i>p</i> ≤ 0.004). For mianserin, the C/D ratio was 80% and 45% higher in PMs and IMs, respectively, compared with NMs (<i>p</i> &lt; 0.001). The C/D ratio in UMs did not differ from NMs for either drug (<i>p</i> ≥ 0.3). In conclusion, <i>CYP2D6</i> genotype was only associated with a minor change in mirtazapine serum concentration. The association between <i>CYP2D6</i> genotype and mianserin serum concentration was greater, with 80% higher mianserin C/D ratio in CYP2D6 PMs compared with NMs.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497122","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":"Filgotinib Improves Experimental Pulmonary Fibrosis by Modulating JAK1/STAT3/SOCS3/IL-17A Signalling","authors":"Yunying Lv,&nbsp;Guanghua Zhang,&nbsp;Dexin Kong,&nbsp;Wanglin Jiang","doi":"10.1111/bcpt.70012","DOIUrl":"https://doi.org/10.1111/bcpt.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Regulatory agencies in Europe and Japan have approved filgotinib, a selective JAK1 inhibitor, for use in treating rheumatoid arthritis, but its effect and mechanism of action in treating pulmonary fibrosis remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an in vivo investigation in rats on filgotinib's effect on pulmonary fibrosis resulting from the intratracheal infusion of bleomycin (BLM). Then, we focused on the mechanisms by which filgotinib inhibits experimentally induced pulmonary fibrosis in vitro by determining its effect on TGF-β1-induced proliferation of mouse lung fibroblasts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Continuous gavage of filgotinib at 20 mg/kg for 14 days elicited protective effects in the BLM-induced rat experimental pulmonary fibrosis model, as reflected in changes in Hounsfield units as an indicator of overall pulmonary function and in the lung coefficient and lung microscopic pathology scores as indicators of gross pulmonary pathology. Protein expression levels of IL-17A, phosphorylated tyrosine kinase (p-JAK1), p-STAT3 and cytokine signal transduction inhibitor 3 (SOCS3) were also changed. In in vitro studies, filgotinib at 1 μM reduced TGF-β1-induced fibroblast proliferation and produced lower levels of IL-17A, p-JAK1 and p-STAT3, but higher SOCS3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Filgotinib appeared to alleviate experimental pulmonary fibrosis by reducing fibroblast proliferation via inhibition of the JAK1/STAT3/SOCS3/IL-17A pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481596","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":"Genetic and Functional Characterization of DPYD Exon 4 Deletion Common in the Finnish Population","authors":"Johanna I. Kiiski,&nbsp;Sofia Khan,&nbsp;Antti Hosio,&nbsp;Mikko Neuvonen,&nbsp;Mikko Niemi","doi":"10.1111/bcpt.70011","DOIUrl":"https://doi.org/10.1111/bcpt.70011","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475521","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":"Predictive Biomarkers and Personalized Therapy: Use of Pharmacogenetic Testing in a Scandinavian Perspective","authors":"Niels Westergaard,&nbsp;Trine Meldgaard Lund,&nbsp;Charlotte Vermehren","doi":"10.1111/bcpt.70009","DOIUrl":"https://doi.org/10.1111/bcpt.70009","url":null,"abstract":"<p>Precision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446814","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":"Ameliorative Role of β-Caryophyllene on Antioxidant Biomarkers in a Paroxetine-Induced Model of Male Sexual Dysfunction","authors":"Elijah Oluwatosin Olopade,&nbsp;Stephen Adeniyi Adefegha,&nbsp;Jude Oluwapelumi Alao,&nbsp;Ayodeji Emmanuel Adepoju,&nbsp;Aderonke Elizabeth Fakayode,&nbsp;Ganiyu Oboh","doi":"10.1111/bcpt.70010","DOIUrl":"https://doi.org/10.1111/bcpt.70010","url":null,"abstract":"<p>Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424071","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":"Correction to “The Protective Effect of Modafinil on Vincristine-Induced Peripheral Neuropathy in Rats: A Possible Role for TRPA1 Receptors”","authors":"","doi":"10.1111/bcpt.70006","DOIUrl":"https://doi.org/10.1111/bcpt.70006","url":null,"abstract":"<p>We apologize for the adjustments.</p><p>We apologize.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424000","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":"Tetrahydroxy Stilbene Glycoside Reduces Abeta Deposition by Modulating Microglia Activation and via TREM2/PI3K/AKT Pathway in APP/PS1 Mice","authors":"Ming Li,&nbsp;Qihan Song,&nbsp;Shanshan Jie,&nbsp;Chenchen Wang,&nbsp;Can Zhang,&nbsp;Kexin Chi,&nbsp;Yan Gao,&nbsp;Tianzuo Li","doi":"10.1111/bcpt.70008","DOIUrl":"https://doi.org/10.1111/bcpt.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Tetrahydroxy stilbene glycoside (TSG), which is the primary active substance of Chinese herbal medicine called <i>Polygonum multiflorum</i>, has been acknowledged to alleviate Alzheimer's disease (AD)-induced learning disorder in the transgene mice. Because the microglia activation is really important during the AD progression, herein, we determined the effects of TSG on AD neuropathology, microglia polarization and its underlying mechanism. We used APP/PS1 mice along with immunohistochemistry and immunofluorescence techniques to evaluate the function of TSG as 60, 120 and 180 mg/kg on Aβ deposition, neuronal loss and microglia polarization induced by AD. Additionally, we assessed the effects of TSG on TREM2 signalling using both molecular docking and Western blot analysis. TSG was found to promote neuronal survival and decrease Aβ deposition in APP/PS1 mice. Moreover, TSG reduced microglia M1 polarization and modulated the TREM2/PI3K/AKT signalling pathways. TSG could reduce neuronal impairment by mediating the microglia polarization by TREM2/PI3K/AKT signalling pathway in APP/PS1 mice and is a latent pharmacological research direction for the therapy in the patients with AD.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404712","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}