Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Association Between Furosemide and Risk of Parkinson's Disease in a Nested Case-Control Study.","authors":"Barkat Babar, Anne Paakinaho, Emeline Courtois, Isabell Rumrich, Yanis Saidi, Alexis Elbaz, Anne C M Thiébaut, Ismaïl Ahmed, Miia Tiihonen, Sirpa Hartikainen, Anna-Maija Tolppanen","doi":"10.1111/bcpt.70249","DOIUrl":"10.1111/bcpt.70249","url":null,"abstract":"<p><p>A French signal detection study identified an association between sulfonamide diuretics use, particularly furosemide, and lower Parkinson's disease (PD) risk. Our aim was to confirm this association in a Finnish nationwide nested case-control study (FINPARK), primarily in an indication-restricted case-control study of persons with heart or renal failure. Altogether 19 568 PD cases diagnosed in 1999-2015 and 130 156 age, sex and region-matched controls were included. The case-control study restricted to those with heart or renal failure included 1222 PD cases and 4766 matched controls. Furosemide use was identified from Prescription Register (1995-2015). The main analysis considered exposure at least 3 years before the matching date (3-year lag). Additional analyses with no lag, 5- and 8-year lags were conducted. Furosemide was not associated with PD risk (adjusted OR, 95% CI 1.00, 0.87-1.15 for user-non-user comparison with 3-year lag). A statistically significant borderline association between higher exposure levels and lower PD risk was observed in comparing risk across categories of cumulative furosemide exposure (adjusted OR, 95% CI 0.80, 0.64-1.00 with 3-year lag). Our nationwide indication-restricted case-control study of persons with PD found no robust evidence on the association between furosemide use and PD risk. However, there was suggestive evidence of reduced risk for participants in the highest exposure category.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70249"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986311","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":"Maternal Dyslipidaemia Aggravates Offspring Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Kamilla Pedersen, Sanne Fredslund Buhl, Cecilie Højgaard-Jensen, Jens Lykkesfeldt, Pernille Tveden-Nyborg","doi":"10.1111/bcpt.70235","DOIUrl":"10.1111/bcpt.70235","url":null,"abstract":"<p><p>Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) display a distinct and severe histopathology. Maternal metabolic status may program offspring susceptibility to MASLD. This study investigated if maternal dyslipidaemia and low vitamin C (VitC) status influence offspring MASLD using a validated guinea pig model. Thirty female guinea pigs received a low-fat (LF) diet until pregnancy was confirmed, then remained on LF or switched to a high-fat (HF) diet with or without reduced VitC. Offspring were evaluated at birth and after 10 weeks on postweaning HF or LF diets. In dams, HF diet induced dyslipidaemia and elevated hepatic triglycerides and alanine aminotransferase (ALT) compared to LF dams, without causing obesity. Newborns exposed to maternal HF diet showed increased hepatic triglycerides, liver-to-body weight ratio and ALT. By 10 weeks, liver fibrosis and MASLD activity scores were higher in offspring maintained on a postnatal HF diet compared to LF. Notably, offspring viability was markedly reduced on maternal HF diet with low VitC. These findings demonstrate that even short exposure to maternal HF diet, independent of obesity, can adversely affect offspring MASLD risk and highlight the need for early prevention. Additionally, findings support the need to investigate interactions between maternal diet, VitC status and offspring survival.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70235"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855839","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":"Genomic and Sex Contributions to Interindividual Variability in Pitavastatin Bioavailability","authors":"Eva González-Iglesias,&nbsp;Sofía Moreno-Pérez de Villar,&nbsp;Dolores Ochoa,&nbsp;Manuel Román,&nbsp;Jesús Novalbos,&nbsp;Samuel Martín-Vilchez,&nbsp;Alejandro de Miguel,&nbsp;Francisco Abad-Santos","doi":"10.1111/bcpt.70251","DOIUrl":"10.1111/bcpt.70251","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study investigates pharmacogenetic determinants of pitavastatin disposition using a candidate-gene approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 48 healthy volunteers, 138 variants across 40 genes involved in drug metabolism and transport were analysed to assess their relationship with pitavastatin pharmacokinetics, alongside the influence of sex and biogeographical origin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Women exhibited 35% higher AUC and <i>C</i>_<i>max</i> values than men; however, these differences disappeared after adjusting for the dose/weight (DW) ratio, with only a 22% increase in <i>t</i>_1/2 remaining. The most prominent finding was the 50%–65% increase in AUC/DW and <i>C</i>_<i>max</i>/DW observed in decreased function (DF) individuals compared with increased function (IF) and normal function (NF) carriers of SLCO1B1 phenotype, reinforcing its role as the primary hepatic uptake transporter for pitavastatin. Additional variants in efflux transporters such as <i>ABCB1</i>, <i>ABCC3</i> and <i>ABCG2</i> may also contribute to interindividual variability, albeit to a lesser extent. Among drug-metabolising enzymes, CYP4F2 emerged as a candidate for further investigation, given the 36% reduction in AUC_48h/DW associated with the rs3093200 variant. No significant associations were detected for <i>CYP2D6</i> or <i>CYP2C9</i> genes. Evidence to date does not indicate a meaningful impact of UGT enzymes on pitavastatin pharmacokinetics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, these findings highlight several genetic factors that may modulate pitavastatin disposition, warranting confirmation through functional studies or larger population cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052003","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":"Transient Receptor Potential Channels in Modulating Synaptic Plasticity and Cognitive Function: Potential Role of Pharmacological Agents","authors":"Abhishek Sarkar,&nbsp;Krishnamoorthy Srinivasan,&nbsp;Ashok Kumar Datusalia,&nbsp;Shyam Sunder Sharma","doi":"10.1111/bcpt.70248","DOIUrl":"10.1111/bcpt.70248","url":null,"abstract":"<p>Cognitive impairment represents the most prevalent complication of neurological diseases (NDs), which significantly affects the quality of life in affected patients. Current treatments primarily target neurotransmitter imbalances but do not act on the key pathological events such as Ca²⁺ dyshomeostasis, oxidative stress, microglia activation, mitochondrial dysfunction and neuroinflammation that occur in the brain of patients with NDs. Therefore, existing treatments fail to stop the progressive cognitive decline in these diseases. Thus, there is a critical need for literature which covers the potential novel therapeutic targets along with their modulators for the effective treatment of cognitive impairment associated with NDs. Recently, transient receptor potential (TRP) channels have emerged as key regulators of these pathological events implicated in ND-associated cognitive impairment. Many preclinical studies have demonstrated that pharmacological modulation of specific TRP channels can improve cognitive function in animal models of NDs. However, clinical translation of TRP channel modulators is still constrained due to a lack of subtype specificity, limited clinical data and difficulties in drug delivery across the blood–brain barrier (BBB). In the present review, we have discussed the structural diversity of TRP channels, their role in regulating synaptic plasticity and cognitive function, and their potential as pharmacological targets for the treatment of cognitive impairment, which can provide a direction for future research in this field.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040966","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":"Evidence for a Two-Step Model for Activation of GPR25 by the Chemoattractant CXCL17","authors":"Wuqing Yang,&nbsp;Sean P. Giblin,&nbsp;James E. Pease","doi":"10.1111/bcpt.70255","DOIUrl":"10.1111/bcpt.70255","url":null,"abstract":"<p>CXCL17 was recently reported to activate GPR25, a receptor expressed by T-regulatory cells. Although classified as a chemokine, the activity of CXCL17 is ablated by minor C-terminal truncation, suggesting a novel mode of receptor activation. We set out to test this hypothesis by mutagenesis. GPR25 was expressed in the murine pre-B cell line L1.2 and mediated robust migration of transfectants to nanomolar concentrations of recombinant CXCL17 (24–119). The N-terminally truncated form of CXCL17 (64–119) was also chemotactic for GPR25 transfectants, albeit with severely reduced potency. Modelling of CXCL17:GPR25 implied multiple interactions between the N- and C-termini of CXCL17 with GPR25, which was validated by mutagenesis. Cells expressing a chimeric FPR1:GPR25 construct responded chemotactically to CXCL17 but with significantly reduced potency compared with wild-type GPR25 transfectants, implicating the GPR25 N-terminus in CXCL17 recognition. Mutagensis of the GPR25 residues W95, R178 and R264 resulted in a complete loss of chemotactic responsiveness to CXCL17, consistent with the residues interacting with the C-terminal CXCL17 motif. In conclusion, we verify GPR25 as a bona fide CXCL17 receptor and suggest a two-step model of GPR25 activation, in which the receptor N-terminus orients CXCL17 for activation of GPR25 via its C-terminus. We also advocate the reclassification of CXCL17 as a chemoattractant distinct from the chemokine family.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040946","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148091035","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148089174","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148089220","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148089221","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148088326","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}