Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Curcumin Alleviates Myocardial Ischaemia-Reperfusion Injury by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis via the Nrf2/HO-1 Pathway: An Integrated Network Pharmacology and Experimental Study.","authors":"Lingling Yao, Jun Qin, Jun Shen, Fusheng Zhang, Jinghua Liu","doi":"10.1111/bcpt.70232","DOIUrl":"10.1111/bcpt.70232","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to screen potential targets of Curcumin (Cur) in Myocardial ischaemia-reperfusion injury (MIRI) using network pharmacology and molecular docking, and to experimentally validate whether Cur mitigates MIRI by modulating the NLRP3 inflammasome and pyroptosis via the Nrf2/HO-1 pathway.</p><p><strong>Methods: </strong>Potential Cur-MIRI targets were identified from public databases and analysed by topological algorithms; molecular docking assessed binding affinity. Cardioprotective effects were validated in vivo using a murine LAD ligation model (30 min ischaemia/24 h reperfusion) and in vitro using H9C2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R). Cur was given as pretreatment. Mechanistic assays included tissue immunofluorescence, mtROS and JC-1 staining, ELISA for cytokines, and Western blotting; Nrf2 was silenced by siRNA to test dependency.</p><p><strong>Results: </strong>Network analysis revealed 481 common targets enriched in apoptosis, TNF and NOD-like receptor pathways. Docking showed favourable binding to NLRP3 (-8.14 kcal/mol) and Nrf2 (-7.02 kcal/mol). In vivo Cur reduced myocardial injury markers, improved echocardiographic function, attenuated inflammation and mitochondrial ultrastructural damage, and decreased NLRP3/caspase-1 expression. In vitro Cur lowered IL-1β/IL-18 and mtROS, preserved mitochondrial membrane potential, reduced apoptosis, upregulated Nrf2/HO-1 and downregulated pyroptosis proteins (NLRP3, ASC, caspase-1, GSDMD). Nrf2 silencing abolished these effects.</p><p><strong>Conclusion: </strong>Combining in silico and experimental evidence, Cur attenuates MIRI by activating Nrf2/HO-1 to inhibit NLRP3 inflammasome-mediated pyroptosis.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70232"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761012","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":"Mechanistic Biomarker Discovery of Perfluorooctanoic Acid Exposure in Parkinson's Disease Through Integrated Toxicogenomic Analysis.","authors":"Peng Yan, Xinyu Du, Leshan Xiu","doi":"10.1111/bcpt.70250","DOIUrl":"10.1111/bcpt.70250","url":null,"abstract":"<p><p>Perfluorooctanoic acid (PFOA) is a common polyfluoroalkyl substance (PFAS) with possible neurotoxic effects, but its role in Parkinson's disease (PD) is not clear. We aimed to identify shared genes and pathways that link PFOA to PD, to test if the link is causal and to develop blood-based biomarkers for case identification. Using the Comparative Toxicogenomics Database (CTD), we found 62 genes common to both PFOA and PD, which were enriched in pathways related to oxidative stress, xenobiotic metabolism and neurodegeneration. Mendelian randomization and colocalization analyses identified BST1 as a key gene, where higher BST1 expression was causally linked to increased PD risk (OR = 1.41, p = 0.001). The eQTL and PD signals shared a lead variant (rs4389574; PP.H4 = 0.980), confirming a common genetic origin. We built a cross-sectional case identification model from Parkinson's Progression Markers Initiative (PPMI) whole-blood RNA-seq using PFOA-linked genes. It achieved moderate discrimination (OOF AUC 0.625) and surpassed a demographic baseline (AUC 0.498); external validation without refitting produced AUCs of 0.642 (GSE6613) and 0.632 (GSE99039). Finally, we explored potential protein-chemical interactions in silico. Molecular docking and dynamics simulations demonstrated that PFOA can maintain stable binding within the BST1 pocket, providing a structural hypothesis for future experimental validation.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70250"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969928","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":"Vitamin D3 Neuroprotection Against Rotenone and MPTP in SH-SY5Y Cells.","authors":"Ekramy M Elmorsy, Ayat B Al-Ghafari, Huda A Al Doghaither, Nagwa M Aly, Mai A Salem, Eman A Toraih, Manal S Fawzy, Shaimaa A Shehata","doi":"10.1111/bcpt.70237","DOIUrl":"10.1111/bcpt.70237","url":null,"abstract":"<p><p>Environmental neurotoxicants such as rotenone (RO) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are known to induce cytotoxicity in neural cells. This study aimed to investigate the neuroprotective properties of active vitamin D3 against the cytotoxic effects of RO and MPTP on undifferentiated human neuroblastoma (SH-SY5Y) cells. Exposure to these neurotoxins resulted in concentration- and time-dependent reductions in cell viability. Cotreatment with vitamin D significantly mitigated the cytotoxic impact of both compounds. Furthermore, vitamin D attenuated disruptions in noradrenaline turnover and acetylcholinesterase activity caused by neurotoxin exposure. Mechanistic exploration revealed that vitamin D preserved cellular bioenergetics by maintaining ATP levels, supporting Mitochondrial Complexes I and III activities, stabilizing mitochondrial membrane potential and reducing lactate accumulation. Vitamin D also reduced oxidative stress, as evidenced by lower reactive species production and lipid peroxidation, while enhancing catalase (CAT) activity in treated cells. In addition, vitamin D counteracted the upregulation of neurodevelopmental genes CAMK2A and CAMK2B induced by neurotoxin exposure. Collectively, these findings demonstrate that vitamin D3 confers significant neuroprotection against RO- and MPTP-induced toxicity in SH-SY5Y cells by modulating mitochondrial function, oxidative stress and neurochemical balance. These results support the potential therapeutic use of vitamin D3 to prevent or ameliorate neurodegenerative conditions and other neurological disorders characterized by mitochondrial dysfunction and oxidative damage.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70237"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810007","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":"Relaxation of Guinea Pig Aorta Induced by 5-HT_2B Receptor. Exploration of Potential Mechanisms.","authors":"Sergio Del-Ángel-Monroy, Aniller Rodríguez-Márquez, Sandra Orozco-Suárez, Verónica Carbajal, Ana Lilia Torres-Machorro, Angélica Vega-García, Patricia Segura-Medina, Mario H Vargas, Patricia Campos-Bedolla","doi":"10.1111/bcpt.70236","DOIUrl":"10.1111/bcpt.70236","url":null,"abstract":"<p><p>Vascular relaxation induced by 5-HT_2B receptor is thought to be mediated by stimulation of endothelial nitric oxide synthase (eNOS), but this assumption still requires investigation. To investigate potential mechanisms, BW723C86 (5-HT_2B receptor agonist) was added to guinea pig aorta rings precontracted by KCl, phenylephrine (Phe) or 5-hydroxytryptamine (5-HT). The effect of N^ω-nitro-L-arginine methyl ester (L-NAME) (NOS inhibitor), charybdotoxin (potassium channels blocker) or endothelium removal on the BW723C86 response was also explored. 5-HT_2B receptor expression was evaluated through immunofluorescence and NOS expression by means of qPCR and ELISA. Stimulation of the 5-HT_2B receptor relaxed all precontracted aorta rings, and L-NAME fully abolished such relaxations, while charybdotoxin prevented the relaxation only in aortas precontracted by Phe or 5-HT. Immunolabelling confirmed a strong expression of the 5-HT_2B receptor in endothelium and much less in smooth muscle. Interestingly, BW723C86 was still able to produce relaxation on endothelium-denuded aortas precontracted by KCl or Phe but caused a potent contraction on 5-HT precontracted aortas. Because it is known that NOS activity is upregulated by KCl and Phe, but downregulated by 5-HT, we explored whether smooth muscle NOS could be responsible for these effects, but L-NAME did not prevent it. These results pointed out that mechanisms other than NOS activation are also involved in the relaxing effect of 5-HT_2B receptor stimulation.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70236"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761043","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":"Multi-Omics Profiling Reveals PDK4 as a Key Regulator of Acute Lung Injury in Glufosinate-Ammonium Poisoning.","authors":"Hui Jiang, Cheng Qian, Chao Nie, Ling Yang, Yue Gong, Linghu Cai, Minghua Liu","doi":"10.1111/bcpt.70239","DOIUrl":"10.1111/bcpt.70239","url":null,"abstract":"<p><p>Glufosinate-ammonium (GA) is a widely utilised herbicide. With the gradual phase-out of highly toxic herbicides, the usage rate of GA as an alternative herbicide has significantly increased, which has led to a rise in GA poisoning incidents. In this study, an acute GA poisoning mouse model was constructed and integrated transcriptomic, proteomic and functional experiments to systematically elucidate the molecular mechanisms underlying GA-induced acute lung injury. For the first time, pyruvate dehydrogenase kinase 4 (PDK4) was identified as a potential therapeutic target. Our findings demonstrated that GA poisoning significantly impaired lung tissue structure and inflammatory balance in mice, characterised by alveolar damage, increased neutrophil infiltration, elevated levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) and reduced levels of anti-inflammatory factors (IL-10). Transcriptomic and proteomic analyses revealed significant upregulation of PDK4 at both gene and protein levels, indicating its pivotal role in GA-induced lung injury. Further experimentation showed that the PDK4 inhibitor (PDK4-IN-1) could markedly reduce neutrophil infiltration, restore the balance of pro-inflammatory and anti-inflammatory factors and mitigate pathological lung tissue damage. In conclusion, this study revealed the core position of PDK4 in GA-induced lung injury, providing a theoretical basis for the treatment of GA-induced lung injury. Given the safety of PDK4 inhibitors in preclinical tumour models, the potential for further study is noteworthy.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70239"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986350","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":"Evaluation of a Pharmacist-Led Intervention Focused on the Deprescribing of Cardiovascular and Antidiabetic Medication in Older Patients With Polypharmacy: Patients' and Pharmacists' Experiences.","authors":"Jamila Abou, Petra J M Elders, Rob van Marum, Jacqueline Hugtenburg","doi":"10.1111/bcpt.70241","DOIUrl":"10.1111/bcpt.70241","url":null,"abstract":"<p><strong>Background: </strong>In the Netherlands, community pharmacists (CPs) are required to conduct annual clinical medication reviews (CMRs) for older patients with polypharmacy. In practice, these reviews are insufficiently implemented, and opportunities to deprescribe inappropriate cardiovascular and antidiabetic medications are often missed. The LeMON study focused on deprescribing, enhancing CPs' awareness and ability to reduce unnecessary medication through close collaboration with general practitioners (GPs).</p><p><strong>Aim: </strong>The aim of the study was to evaluate the experiences of patients and CPs who participated in the LeMON study.</p><p><strong>Methods: </strong>Patient experiences and satisfaction were assessed using the Patient-Reported Experience Measure (PREM) and the Treatment Satisfaction Questionnaire for Medication (TSQM). Semistructured interviews with CPs were analysed using the extended normalization process theory (eNPT), covering potential, capability, capacity and contribution.</p><p><strong>Results: </strong>Of 140 patients, 62 (44%) completed the questionnaires. Patients reported high satisfaction, felt their medication concerns were addressed andappreciated CP recommendations. TSQM scores were moderate to high across effectiveness, side effects, convenience andoverall satisfaction. CPs valued the online training and acknowledged the importance of deprescribing. Challenges included addressing patient concerns in the absence of symptoms and deprescribing medications initially prescribed by specialists, which could reduce CPs' confidence and patient trust.</p><p><strong>Conclusion: </strong>Patient and CP experiences highlight the need for specific knowledge and training, shared clinical data andclose CP-GP collaboration to implement deprescribing-focused CMRs routinely. Addressing patient concerns and deprescribing specialist-initiated medications requires effective communication skills and structured local or regional protocols for multidisciplinary collaboration between primary and secondary care.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70241"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925842","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":"Effects of Chemotherapeutic Agents (5-Fluorouracil, Cisplatin and Methotrexate) on Cell Adhesion Molecules and Oxidative Damage Markers in Rat Kidney Tissue.","authors":"Serdar Emre Ozyapici, Melek Ozturkler Dundar, Onur Atakisi","doi":"10.1111/bcpt.70244","DOIUrl":"10.1111/bcpt.70244","url":null,"abstract":"<p><p>Chemotherapeutic drugs are widely used in cancer treatment; however, their limited selectivity often causes toxicity in nontarget organs, particularly the kidneys. The relationship between chemotherapy-induced oxidative stress and cell adhesion mechanisms in renal tissue remains poorly understood. Therefore, this study investigated the effects of three commonly used chemotherapeutic agents-5-fluorouracil (5-FU), cisplatin (CIS) and methotrexate (MTX) on oxidative stress biomarkers and adhesion-related proteins in rat kidney tissue. Twenty male Sprague-Dawley rats were randomly assigned to four groups: control, 5-FU (200 mg/kg), CIS (10 mg/kg) and MTX (50 mg/kg). Kidney samples were collected 24 h after administration under ketamine-xylazine anaesthesia. Tissue levels of 8-OHdG, NO, ADA, GSH and MDA were determined. Protein expression of E-selectin, caspase-3 and β1-integrin in kidney tissue was evaluated using Western blotting. All treatment groups showed increased levels of 8-OHdG, NO, ADA and MDA in kidney tissue, whereas GSH levels were reduced. The highest oxidative damage was observed in the CIS group. Western blot results demonstrated increased expression of E-selectin, caspase-3, and β1-integrin, with strongest increases detected in the MTX group. These findings indicate that 5-FU, CIS and MTX induce oxidative stress, DNA damage and alterations in apoptosis- and adhesion-related pathways in renal tissue, suggesting drug-specific mechanisms underlying chemotherapy-associated nephrotoxicity.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70244"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873262","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":"Protective Effect of Vitamin E Against Vancomycin-Induced Nephrotoxicity: A Large-Scale Electronic Medical Record Study From Japan.","authors":"Satoru Nakanishi, Shungo Imai, Megumi Saito, Hayato Kizaki, Haru Iino, Masami Tsuchiya, Satoko Hori","doi":"10.1111/bcpt.70245","DOIUrl":"10.1111/bcpt.70245","url":null,"abstract":"<p><p>Vancomycin (VCM) is essential for treating methicillin-resistant Staphylococcus aureus infections, but its use is limited by vancomycin-induced nephrotoxicity (VIN). Although preclinical and small clinical studies suggest a protective role for vitamin E, real-world evidence remains limited. We conducted a retrospective cohort study using a large-scale Japanese electronic medical record database including adult patients who received intravenous VCM between 1996 and 2022. VIN was defined according to Kidney Disease Improving Global Outcomes criteria. The association between concomitant vitamin E use and VIN was evaluated using propensity score matching based on logistic regression and light gradient boosting machine models, followed by Kaplan-Meier analysis and Cox proportional hazards regression. Robustness was examined using three analytical strategies, including adjustment for concomitant medications. Among 12 411 eligible patients, 2267 (18.3%) developed VIN and 116 (0.9%) received vitamin E. After matching, vitamin E use was associated with a 10% lower incidence of VIN. Kaplan-Meier analysis showed significantly lower cumulative incidence in the vitamin E group in two approaches. Across 63 Cox models, vitamin E consistently demonstrated a protective trend. These findings support the potential preventive role of vitamin E in maintaining VCM therapy.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70245"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986336","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":"The Cardiovascular Safety of Antiparkinsonian Drugs-Analysis of Signals in the FDA Adverse Event Report System Database.","authors":"Xin Mu, Yanfeng Wang, Peiyao Wei, Junwei Ren, Pingping Ning","doi":"10.1111/bcpt.70242","DOIUrl":"10.1111/bcpt.70242","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the characteristics and spectrum of cardiotoxicity induced by various antiparkinsonian drugs based on the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>Data from the FAERS database from the first quarter of 2004 to the third quarter of 2025 were downloaded for disproportionality analysis. We employed validated disproportionality metrics including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) to detect significant drug-event associations.</p><p><strong>Results: </strong>After removing duplicates, a total of 42 583 cases of patients treated with antiparkinsonian drugs were included in the FAERS database. Dopamine receptor agonists exhibited the most extensive range of cardiac adverse events. Monoamine oxidase B inhibitors displayed the second broadest range of toxicity. As for catechol-O-methyltransferase inhibitors, a total of six signals were detected in entacapone. Four signals were detected for amantadine, while no signals were identified for levodopa.</p><p><strong>Conclusion: </strong>This study highlights the cardiovascular adverse reactions associated with Parkinson's treatment drugs. These findings underscore the importance of monitoring and evaluating the cardiovascular safety of antiparkinsonian medications.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70242"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809829","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":"Environmental Aspects in Price and Reimbursement Decisions of Medicines-A Scoping Review.","authors":"Lasse Alajärvi, Mirella Miettinen, Johanna Timonen","doi":"10.1111/bcpt.70243","DOIUrl":"10.1111/bcpt.70243","url":null,"abstract":"<p><p>Environmental impacts of medicines are increasingly recognised but rarely embedded in their pricing and reimbursement (P&R) and related assessments. This scoping review mapped how environmental aspects, including antimicrobial resistance (AMR) stewardship, are or could be considered in P&R of medicines and identified challenges for their implementation. Electronic searches from PubMed, Scopus, Web of Science, Edilex, HeinOnline, Westlaw, Google Scholar and official agencies' websites were conducted. Eligible items covered developed country settings and described existing or proposed integration of environmental aspects into medicine pricing or reimbursement. Of 4476 publications, 21 were included. The publications were from 2013 to 2023, most of them addressing ecotoxicological and climate impacts. Six types of means to embed environmental aspects into P&R were identified: health technology assessment (HTA) integration, reimbursement criteria, pricing criteria, environmental classification, regulation and delinkage models. Most proposals were conceptual, whereas implemented or piloted examples focused on AMR-oriented means. Reported challenges for implementation included challenges regarding data availability, comparability and verification; valuation and methodological integration; incentive design and cost distribution; and equity and political feasibility. Environmental aspects are not yet routine in medicine P&R assessments due to a lack of standardised, verifiable product-level data, appraisal methods and equity-sensitive policy design.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70243"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866559","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}