BMC Pharmacology & Toxicology最新文献

{"title":"Combined purslane ethanolic extract and metformin attenuate cognitive dysfunction in HFD/STZ-induced diabetic rats via modulation of oxidative stress, neuroinflammation, and neurotransmitters.","authors":"Naglaa Bahr, Abd El-Kader M Abd El-Kader, Alaa Eldin Salah Eldin, Eatemad A Awadalla, Maha A El Demellawy, Doaa A Ghareeb","doi":"10.1186/s40360-026-01128-w","DOIUrl":"10.1186/s40360-026-01128-w","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is associated with a number of significant long-term effects. In this study we consider that purslane which possesses numerous of pharmacological properties, and metformin, an antidiabetic drug, may have a therapeutic effects on diabetes-induced memory impairments in rats.</p><p><strong>Methods: </strong>Forty male albino rats were randomly divided into five groups. Group I served as control group. The other four groups were first fed on HFD followed by a single interpretonial (i.p.) dose of STZ at a dose of (35) mg/kg then the groups were divided as following Group II diabetic group Group III, PEE group administered with oral dose of purslane ethanolic extract (100 mg/kg) for another four weeks. Group IV, MET group administered with oral dose of metformin (100 mg/kg) for another four weeks. Group V (PEE + MET) administered with oral dose of combination of both purslane ethanolic extract (50 mg/kg) and MET (50 mg/kg) for another four weeks. During the treatment rats were tested for memory and learning abilities (Morri's water maze test). Hippocampal samples were collected for biochemical, and histological measurements. Biochemical evaluation included (NO and TBARS) as an oxidative stress marker, (GSH, GPX, SOD, Catalase) as antioxidant, and inflammatory cytokines (tumor necrosis factor-α and interleukin-1β, interleukin-IL-6). Also, P-tau protein, (dopamine and GABA) as neurotransmitters, and for cholinergic system (acetylcholinesterase) were assessed, in addition to histological examinations of hippocampus.</p><p><strong>Results: </strong>Diabetic rats showed a marked cognitive impairment in the Morris water maze test and alteration in the other biochemical and histological features. Intrestingly, PEE and MET treatments partially dramatically enhanced antioxidant levels. Also, reduced oxidative stress, pro-inflammatory mediators, and, phosphorylated tau levels. In addition, PEE and MET treatments partially modulated neurochemical profiles associated with memory function. The combined PEE + MET treatment showed the most pronounced improvement, reflecting synergistic effects. Individual data points highlighted consistent trends across animals. Also, it exhibited a significant restoration of normal hippocampal architecture, as confirmed by hematoxylin and eosin staining.</p><p><strong>Conclusions: </strong>The data obtained indicated that PEE, either alone or in combination with MET, has strong neuroprotective potential against STZ/HFD-induced diabetes. These safeguarding effects are probably because of its strong anti-inflammatory and antioxidant properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810728","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":"The potential mechanisms of LCZ696 for anti-hyperthyroid heart disease: an integrative approach of network pharmacology, molecular docking and in vivo verification.","authors":"Xianghui Zeng, Lihua Wen, Luoying Liu, Qingfeng Zeng, Jianping Luo","doi":"10.1186/s40360-026-01145-9","DOIUrl":"https://doi.org/10.1186/s40360-026-01145-9","url":null,"abstract":"<p><strong>Backgroud: </strong>Hyperthyroid heart disease (HHD) is characterized by cardiac remodeling and inflammation, yet targeted therapies remain limited. LCZ696 (sacubitril/valsartan) has demonstrated cardioprotective effects, but its mechanisms in HHD are unclear.</p><p><strong>Methods: </strong>In this study, Network pharmacology alongside experimental validation were employed to elucidate the pharmacological mechanisms of LCZ696 in the treatment of HHD. We identified potential targets for LCZ696 and relevant HHD-related genes from public databases. The mechanisms by which LCZ696 exerts its effects on HHD were further elucidated through GO, KEGG and PPI analysis. The potential molecular targets of LCZ696 were evaluated by molecular docking. Additionally, Echocardiography-measured cardiac function, myocardial fibrosis, target Genes and Inflammatory responses of cardiomyocytes in rat were also examined.</p><p><strong>Results: </strong>A total of 78 target genes for LCZ696 and 1520 HHD targets were obtained. 35 overlapping genes were determined as potential targets of LCZ696 in treating HHD. The PPI analyses highlighted targets being associated with HHD as STAT3, STAT1 and MUC1, suggesting potential binding interactions with LCZ696, as verified by molecular docking analysis, which were also consistent with the experimental results.</p><p><strong>Conclusions: </strong>LCZ696 may ameliorate HHD, potentially associated with reduced inflammation and downregulation of STAT3 signaling.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary investigation of the effects of amentoflavone on TNF-α-induced endothelial activation in HUVECs.","authors":"Fatih Can Turk, Burak Onal, Zulal Celik, Ahmet Gökhan Akkan, Sibel Özyazgan","doi":"10.1186/s40360-026-01143-x","DOIUrl":"10.1186/s40360-026-01143-x","url":null,"abstract":"<p><strong>Background: </strong>Endothelial dysfunction characterized by cytokine release and adhesion molecule upregulation is a major driver of atherogenesis. Tumor necrosis factor-α (TNF-α) activates NF-κB signaling and increases ICAM-1, VCAM-1, IL-6, and IL-8 expression in endothelial cells. This study aimed to investigate whether amentoflavone (AMF) modulates TNF-α-induced inflammatory and adhesion-related responses in human endothelial cells, supporting its potential to mitigate early vascular dysfunction.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α (10 ng/mL) in the presence or absence of AMF. Six experimental groups were designed to determine AMF's prophylactic, concurrent, and post-treatment influences on inflammation. Relative mRNA levels of IL-6, IL-8, ICAM-1, VCAM-1, and NF-κB were quantified by qRT-PCR, while protein levels were measured by ELISA.</p><p><strong>Results: </strong>TNF-α markedly increased IL-6, IL-8, ICAM-1, VCAM-1, and NF-κB expression at both the mRNA and protein levels. AMF alone did not trigger any inflammatory response and notably attenuated TNF-α-induced cytokine and adhesion molecule upregulation. Both concurrent and sequential AMF treatments reduced inflammatory responses compared with TNF-α-only cells. Prophylactic AMF administration demonstrated the greatest inhibitory effect, indicating enhanced preventive potential. AMF effectively suppresses TNF-α-mediated endothelial activation by downregulating NF-κB signaling and reducing the expression of IL-6, IL-8, ICAM-1, and VCAM-1.</p><p><strong>Conclusions: </strong>These findings suggest that AMF may represent a promising in vitro preventive candidate against TNF-α-induced endothelial activation, warranting further validation in additional experimental models.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810792","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":"Integrative bioinformatics, network toxicology, and molecular docking elucidate molecular mechanisms of ATBC-induced sarcoma progression with experimental validation.","authors":"Yue Wang, Xuan Lin, Yihuang Chen, Yuanqun Zhang, Qiang Zhang, Miao Xu, Xiaoning Lin, Xin Wu, Shifu Peng, Jianlin Shen","doi":"10.1186/s40360-026-01141-z","DOIUrl":"10.1186/s40360-026-01141-z","url":null,"abstract":"<p><p>BACKGROUND: Acetyl tributyl citrate (ATBC), a widely used plasticizer, has raised health concerns due to its potential environmental persistence and human exposure, but its toxicological effects on sarcoma remain unclear. METHODS: We employed an integrated approach combining network toxicology, molecular docking, survival analysis, and experimental validation to systematically investigate ATBC’s impact on sarcoma. RESULTS: Multi-database screening identified 102 overlapping targets. Protein–protein interaction analysis revealed six hub genes: TLR4, ESR1, PPARG, SIRT1, NFKB1, and PTGS2. Functional enrichment analysis indicated significant involvement in cancer-related pathways, including PI3K–Akt, HIF‑1, and AGE–RAGE signaling. Molecular docking predicted potential interactions between ATBC and these targets, with binding energies ranging from -1.15 to -2.99 kcal/mol. Survival analysis associated high PPARG expression with poor prognosis, while high TLR4 and ESR1 expression correlated with better survival. In vitro experiments showed ATBC promoted proliferation and migration of sarcoma cells. qPCR results confirmed ATBC downregulated TLR4 and ESR1 and upregulated PPARG, aligning with clinical prognostic trends. CONCLUSIONS: These findings suggest ATBC may exert tumor-promoting effects by modulating core targets and pathways, highlighting its potential role in sarcoma progression and the importance of environmental health risk assessment.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761335","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":"CZC54252 overcomes Osimertinib resistance by targeting EGFR^C797S mutations.","authors":"Tingnan Ma, Tao Yuan, Yingying Hou, Maoyu Liu, Yaru Zhang, Jianyou Shi, Lei Zhong","doi":"10.1186/s40360-026-01139-7","DOIUrl":"10.1186/s40360-026-01139-7","url":null,"abstract":"<p><p>BACKGROUND: The introduction of EGFR inhibitors has revolutionized the management of NSCLC, leading to a significant extension of survival in the target patient population. Unfortunately, acquired resistance appears to be unavoidable, which restricts the use of EGFR-TKIs in the clinic. EGFRC797S represents a novel resistant mutation after treatment with the latest generation of EGFR inhibitor Osimertinib. Consequently, developing next-generation EGFR-TKIs targeting such resistant mutations is strongly demanded. METHODS: Osimertinib-resistant NSCLC cell lines were constructed by transfecting EGFRdel19/T790M/C797S or EGFRL858R/T790M/C797S lentiviral plasmids into NSCLC PC-9 cells, followed by puromycin screening. The drug screening was conducted in a drug repurposing compound library provided by TargetMol. The hit compound (CZC54252) was validated by kinase inhibition, western blot, and molecular docking assays. Its role in overcoming Osimertinib resistance was further evaluated by cellular viability, proliferation, and apoptosis tests. Finally, animal studies were conducted in xenograft models to verify the anti-NSCLC effects of CZC54252 in vivo. RESULTS: The cell models resistant to Osimertinib have been successfully established, and CZC54252 was screened as a hit compound that could overcome Osimertinib resistance, with IC50 values of 0.24 ± 0.06 µM and 0.27 ± 0.09 µM on PC-9del19/T790M/C797S and PC-9L858R/T790M/C797S cells, respectively, which were significantly lower than those of Osimertinib (2.1 ± 0.32 µM and 2.8 ± 0.37 µM, respectively). CZC54252 displayed potent inhibitory activity on EGFRdel19/T790M/C797S (IC50: 1.66 nM) and EGFRL858R/T790M/C797S (IC50: 2.92 nM), and significantly repressed EGFR phosphorylation in western blot assay. Additionally, the pharmacodynamics studies demonstrated that CZC54252 moderately suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Notably, not all drug candidates targeting the same molecular pathways as CZC54252 showed activity in the screening, indicating that CZC54252 may overcome Osimertinib resistance by directly targeting EGFRC797S triple mutations rather than its original targets. CONCLUSION: These data indicate that CZC54252 represents a promising lead compound for overcoming Osimertinib resistance by targeting EGFRC797S, which provides a chemical basis for the development of novel fourth-generation EGFR inhibitors.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761270","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":"Integration of multi-omics and network toxicology reveals TLR4-mediated nephrotoxicity induced by arecoline.","authors":"Jixiang Yuan, Lichen Chen, Xilong Wang, Zhibin Jiang, Dian Jin, Yongheng Bai, Xiaodong Pan, Yifu Li, Feihong Lin, Yong Cai","doi":"10.1186/s40360-026-01137-9","DOIUrl":"10.1186/s40360-026-01137-9","url":null,"abstract":"<p><p>BACKGROUND: Arecoline, the primary alkaloid in areca nut, induces renal injury, yet its underlying molecular mechanisms remain poorly understood. This study aimed to identify arecoline’s molecular targets and elucidate the subsequent pathological signaling cascade in renal cells. METHODS: We integrated network toxicology, molecular docking, and molecular dynamics (MD) simulations to predict arecoline’s targets. In vitro validation in human kidney (HK-2) cells assessed target engagement via a cellular thermal shift assay (CETSA). Downstream signaling, inflammatory, and fibrotic markers were evaluated using Western blotting, ELISA, and immunofluorescence. RESULTS: Computational models predicted a stable arecoline-Toll-like receptor 4 (TLR4) complex. CETSA demonstrated that arecoline enhanced TLR4 thermal stability in HK-2 cells, strongly indicating target engagement. This binding activated the PI3K/AKT/NF-κB signaling pathway. Consequently, arecoline induced NF-κB-dependent upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), elevated the renal injury marker KIM-1, and promoted the accumulation of fibrotic proteins (α-SMA, Collagen III). CONCLUSIONS: Arecoline instigates nephrotoxicity by targeting TLR4 and activating the PI3K/AKT/NF-κB axis, driving an inflammatory and fibrotic phenotype in renal tubular cells. The arecoline-TLR4 interaction represents a critical event in areca nut-associated nephropathy, offering a novel therapeutic target.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761267","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":"Assessment of the efficiency of new regenerative gel and spray in experimental model systems.","authors":"Natalia Bezdieniezhnykh, Oleksandra Lykhova, Maryna Borshchevska, Andriy Goy, Kyrylo Saulenko, Tamara Kozak, Dmytro Kukurudza, Yevgen Kruglov, Genadiy Borshchevskiy, Liubov Buchynska","doi":"10.1186/s40360-026-01132-0","DOIUrl":"10.1186/s40360-026-01132-0","url":null,"abstract":"<p><p>INTRODUCTION: The problem of wound healing and the availability of effective and safe agents with regenerative properties is critically important today. The aim of the study was to develop an algorithm for evaluating products with regenerative potential using a set of in vitro and in vivo experimental models. METHODS: In vitro research included methods of working with cell culture. Studies were conducted using cell lines: HaCat, MAEС, 3T3-A31. In vivo research was conducted on Wistar rats with simulation of the pathological condition of a cut wound and the application of experimental samples and the following assessment of a set of indicators. RESULTS: As a result of using a comprehensive approach to assess the effectiveness of agents with regenerative activity, it was shown that the spray and gel samples, the main component of which is collagen, with decamethoxine, particles of silver sulfadiazine, hyaluronic acid, and additionally a set of amino acids in a spray, were shown to cause a statistically significant increase in the number of live cells at certain concentrations in vitro and increase the speed of restoration of the damaged monolayer of endothelial cells. According to the results of the speed of healing of the skin in the area of ​​the simulated cut wound, a statistically significant increase in the speed of healing from 10 to 19% with the use of the spray and from 5 to 18% with the use of the gel in comparison with the animals of the control group (р≤0.05 and p ≤ 0.01). The evaluation of the results of the morphological analysis showed that with repeated application of the spray or gel, a significant reduction in the area of ​​the wound is observed already on the 8th day with faster healing compared to the control. Already from the 8th day, inflammatory changes and the area of ​​necrotic in the experimental groups significantly decreased. CONCLUSION: A wound healing assessment model was developed and tested, which is convenient for monitoring the wound healing process and evaluating treatment outcomes. The efficacy and potential role in accelerating wound healing of new gel and spray products for external use was shown. CLINICAL TRIAL NUMBER: Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688106","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 and in vitro insights into the wound-healing potential of syringic acid: protective and regenerative effects on human fibroblasts.","authors":"Ufuk Okkay, İlkin Kazimov, Irmak Ferah Okkay, Azizeh Shadidizaji, Mehmet Ali Yoruk, Murat Ozdemir, Fatih Burak Yildiz, Fatma Yesilyurt, Mustafa Ozkaraca, Ahmet Hacimuftuoglu","doi":"10.1186/s40360-026-01138-8","DOIUrl":"10.1186/s40360-026-01138-8","url":null,"abstract":"<p><p>This study aimed to investigate the wound-healing potential of syringic acid (SA) through integrated in silico and in vitro approaches using human dermal fibroblasts (HDFs). Network pharmacology analysis identified myeloperoxidase (MPO), a key enzyme involved in oxidative stress and inflammation, as a primary target of SA. Computational predictions also indicated favorable pharmacokinetic and ADMET properties. In vitro experiments were conducted using SA at concentrations of 50–400 µM. Cell viability was assessed by MTT and LDH assays, while antioxidant and inflammatory responses were evaluated by measuring SOD, CAT, MDA, TNF-α, IL-1β, TGF-β, iNOS, and hydroxyproline levels. SA treatment significantly enhanced fibroblast viability and exhibited strong antioxidant effects, as demonstrated by increased SOD and CAT activities and reduced MDA levels. Additionally, SA suppressed pro-inflammatory mediators (TNF-α, IL-1β, and iNOS) while upregulating TGF-β expression. Importantly, SA promoted collagen synthesis, evidenced by increased hydroxyproline content. Among the tested doses, 100–200 µM showed the most pronounced effects. Overall, these findings demonstrate that SA facilitates wound healing by improving cellular viability, reducing oxidative stress and inflammation, and enhancing collagen production. This study highlights SA as a promising multi-target therapeutic candidate for wound repair, although further in vivo and safety studies are required to support its clinical application.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688084","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":"Effects of MDMA treatment and cessation on sexual behaviour and testicular functions in male sprague-dawley rats.","authors":"O O Obembe, E T George, R A Mustapha, R E Akhigbe","doi":"10.1186/s40360-026-01131-1","DOIUrl":"10.1186/s40360-026-01131-1","url":null,"abstract":"<p><p>BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is a psychostimulant known for its social and empathogenic effects. However, its long-term impact on sexual performance and reproductive functions remain controversial. OBJECTIVE: In this study, the effects of chronic MDMA exposure and subsequent withdrawal on sexual behaviour, reproductive hormones, sperm parameters, oxidative stress, systemic inflammation and testicular histology in male rats were investigated. METHODS: Fifteen male rats were divided into three groups (n = 5 rats/group): control (distilled water-treated), MDMA-treated (100 mg/kg orally for 30 days), and MDMA-withdrawal (100 mg/kg of MDMA for 30 days followed by 30-day drug-free recovery). Sexual behaviour was assessed every ten days for 60 days. Epididymal sperm suspension analysis, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, markers of oxidative stress and inflammation interleukins 1beta, 6, and 10 (IL-1β, IL-6, IL-10), tumor necrosis factor-alpha (TNF-α) in serum and testes, and histological evaluations of testes were performed. RESULTS: MDMA significantly enhanced sexual behavioural parameters (mount, intromission, and ejaculation frequencies) during exposure, but these declined with drug withdrawal. Sperm count and motility decreased following MDMA treatment, with partial recovery after withdrawal. Oxidative stress marker (malondialdehyde, MDA) and proinflammatory cytokines (IL-1β, IL-6, TNF-α) were significantly increased while antioxidant enzymes [superoxide dismutase (SOD), catalase, total thiol] were significantly decreased both in the serum and testes. MDMA also suppressed LH, FSH, and testosterone levels, while histological analysis showed reduced spermatid populations, which improved post-cessation. CONCLUSION: MDMA elicits prosexual effects that was accompanied by low epididymal sperm quality, oxidative stress, inflammation, and hormonal suppression during exposure. Nonetheless, partial recovery occurred following MDMA cessation, suggesting potential long-term reproductive risks. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147661969","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":"Protective mechanism of sevoflurane preconditioning on myocardial ischemia-reperfusion injury by regulating RMRP/miR-206 axis.","authors":"Shuang Wu, Yuan Lu, Hao Chen, Shuai Wang, Yanyan Jiang, Dalong Wang, Quan Lin, Ke Liu, Shuai Zhang, Ying Cheng, Xiao Tian, Wenhan Ma","doi":"10.1186/s40360-026-01129-9","DOIUrl":"10.1186/s40360-026-01129-9","url":null,"abstract":"<p><p>OBJECTIVE: Myocardial ischemia-reperfusion injury (MIRI) is a major contributor to global disease mortality. This study aims to investigate the protective mechanism of the RMRP/miR-206 axis in MIRI following sevoflurane (Sev) preconditioning. METHODS: In this study, a hypoxia/reoxygenation (H/R) model was constructed by H9c2 cells. The optimal concentration of Sev was selected by assessing cell viability with a CCK-8 assay. After Sev preconditioning, flow cytometry was employed to detect cell apoptosis. The content of LDH was measured with a lactate dehydrogenase (LDH) assay kit. The SOD activity was examined by an SOD assay kit, and the levels of IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). RT-qPCR was utilized to detect the RMRP and miR-206 expression. The luciferase reporter assay and RIP assay were employed to demonstrate the interaction between RMRP and miR-206. RESULTS: In this study, 2.0% was chosen as the optimal Sev concentration for subsequent experiments. After Sev preconditioning, cell viability increased, apoptosis decreased, LDH levels were reduced, SOD activity was enhanced, IL-6 was downregulated, and IL-10 was upregulated. Meanwhile, RMRP levels decreased significantly after Sev preconditioning. Overexpression of RMRP inhibited the protective effect of Sev preconditioning on H/R-induced cells. Further analysis revealed that RMRP targeted miR-206. While miR-206 increased after Sev preconditioning, RMRP transfection suppressed miR-206 expression. Overexpression of miR-206 rescued H/R-induced cell damage caused by RMRP upregulation. CONCLUSION: Sev preconditioning protects cells from MIRI by regulating the RMRP/miR-206 axis. CLINICAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662096","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}