BMC Pharmacology & Toxicology最新文献

{"title":"Trimetazidine effect on kidney function in patients undergoing coronary procedures.","authors":"Yasser Abdel-Hady, Mohammed Taha, Ahmed El Barbary, Osama Amin","doi":"10.1186/s40360-025-00913-3","DOIUrl":"https://doi.org/10.1186/s40360-025-00913-3","url":null,"abstract":"<p><strong>Background: </strong>CIN (Contrast-induced Nephropathy) was studied after Percutaneous Coronary Intervention (PCI) or Coronary Angiography (CA). Trimetazidine (TMZ) has been investigated as one of the potential molecules that may protect against CIN by its anti-ischemic, antioxidant, and mitochondrial protective effects. We aimed to observe the reno-protective value of TMZ when added to the Guidelines Directed Medical Therapy (GDMT) in patients receiving contrast.</p><p><strong>Methods: </strong>This cohort observational prospective study included 410 patients with Chronic Coronary Syndrome (CCS) undertaking elective CA or PCI. We observed the kidney function following the non-ionic contrast exposure in Group I (205 patients), who received all the GDMT and TMZ. We compared the results with another Group II (205 patients) who received all the GDMT without TMZ. The primary endpoint was the development of CIN, and the secondary endpoint was follow-up kidney function after one month.</p><p><strong>Results: </strong>The baseline characteristics of Group I and Group II were similar, with the weighted groups looking very well matched. All Standardized Mean Differences (SMDs) were either below or very close to 0.1.CIN rates at 72 h were lower in Group I (13.2%) than Group II (22.0%; unadjusted p = 0.019, Bonferroni-adjusted p = 0.352, FDR-adjusted p = 0.047), suggesting a modest protective effect of TMZ that weakens under stringent correction but remains borderline significant with FDR. By one month, CIN rates were 6.3% in Group I vs. 13.2% in Group II (unadjusted p = 0.020, Bonferroni-adjusted p = 0.060, FDR-adjusted p = 0.050), reinforcing TMZ's borderline significant potential long-term benefit.</p><p><strong>Conclusion: </strong>Our Cohort Observational Single-Center study showed that TMZ did not provide robust protection against CIN at 72 h. However, TMZ may offer a modest, clinically relevant, longer-term renal benefit at one month in patients undergoing elective coronary procedures. Further randomized trials are warranted to validate TMZ's efficacy and explore its mechanisms.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"85"},"PeriodicalIF":2.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958307","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":"Sevoflurane reduces cardiomyocyte injury in a hypoxia/reoxygenation model of cardiomyocytes through the linc01278/miR-134-5pt regulatory axis.","authors":"Ling Wang, Changhua Zhu, Yangge Shao, Rui Chen, Hui Liang","doi":"10.1186/s40360-025-00909-z","DOIUrl":"https://doi.org/10.1186/s40360-025-00909-z","url":null,"abstract":"<p><strong>Background: </strong>Ischemia-reperfusion leads to varying degrees of myocardial cell injury. Notably, long noncoding RNA was associated with the protective effect of sevoflurane (Sev) preconditioning against myocardial ischemic injury. Therefore, we further investigated the protective mechanism of Sev-mediated linc01278 against damaged cardiomyocytes by constructing a hypoxia/reoxygenation (HR) model of cardiomyocytes.</p><p><strong>Methods: </strong>The expression of linc01278, miR-134-5p, and apoptotic biomarkers in cardiomyocytes was detected by RT-qPCR. The proliferation was detected by CCK8; apoptosis was observed by flow cytometry; and the degree of cardiomyocyte injury and the level of oxidative stress was observed by ELISA. Dual luciferase reporter assay and RIP verified linc01278 and miR-134-5p interactions.</p><p><strong>Results: </strong>linc01278 was down-regulated in the HR group and up-regulated after Sev pretreatment. Sev markedly mitigated the HR-impaired cell proliferation, reduced apoptosis, and oxidative stress, and downregulated the expression of myocardial injury markers including cTnI, CK-MB, and LDH. However, this protection was noticeably reversed by the downregulation of the linc01278 expression. Mechanistically, linc01278 binds to miR-134-5p. miR-134-5p was highly expressed in cardiomyocytes of the HR, and lowly expressed in the Sev groups. The cardioprotective effect of Sev weakened by si-linc01278 was typically restored by miR-134-5p inhibitor.</p><p><strong>Conclusions: </strong>Sev attenuates HR-stimulated myocardial injury through linc01278/miR-134-5p axis-mediated proliferation, apoptosis, and oxidative stress.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"83"},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979236","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":"Zinc sulphate attenuates metabolic dysfunctions induced by olanzapine via the reduction of insulin resistance, hepatic oxidative stress, and inflammation in albino rats.","authors":"Samir A E Bashandy, Rasha E Mostafa, Marawan A El-Baset, Fatma A A Ibrahim, Fatma A Morsy, Omar A Farid, Halima M Ibrahim, Bassim M S A Mohamed","doi":"10.1186/s40360-025-00889-0","DOIUrl":"https://doi.org/10.1186/s40360-025-00889-0","url":null,"abstract":"<p><p>Olanzapine, an atypical antipsychotic drug, is used to treat psychological diseases. However, it's use carries common side effects. Those include weight gain, dyslipidemia, elevated glucose levels, and disrupted oxidative balance. We aimed to test the effect of zinc coadministration to lessen metabolic disturbances, inflammation and oxidative stress in a rat model. Four treatment groups (n = 6) were involved in this investigation. Group 1 was the control group (received no intervention). Group 2 received olanzapine (10 mg/kg, p.o.; daily) for six weeks, whereas Groups 3 and 4 received 50 mg/kg and 100 mg/kg of zinc sulphate (ZnSO₄,p.o.; daily) respectively, in addition to olanzapine (10 mg/kg p.o.; daily). Following treatment completion, group 2 showed increased levels of stress markers (GSSG, MDA, and NO) and impaired levels of antioxidant markers (CAT, SOD, and GSH). Further, a strong positive correlation between insulin resistance index (HOMA-IR) and IL-6, TNF-α, and MDA of liver. Insulin resistance is a possible manifestation of the oxidative stress burden and the widespread inflammatory environment. In groups 3 and 4, however, ZnSO₄ recovered each of these markers in a dose-dependent manner. Improvements were also noted in other homeostatic markers, such as taurine, coenzyme Q10, ascorbic acid, and vitamin E. Remarkably, in both combination groups, there was a significant improvement in all metabolic indicators of dyslipidemia (triglycerides, total cholesterol) and insulin resistance index. The biochemical study and the histological assessment of the liver slices agreed with the results. Thus, the results clearly suggest that Zinc supplementation can significantly improve oxidative stress, inflammation, metabolic perturbation (dyslipidemia and insulin resistance), and liver injury caused by olanzapine in Albino rats.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"84"},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979281","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":"Can vildagliptin protect against radiation-induced premature ovarian failure? Insights into the AMPK and AKT signaling pathways.","authors":"Nada A Mahgoub, Doaa A El-Sherbiny, Ebtehal El-Demerdash","doi":"10.1186/s40360-025-00903-5","DOIUrl":"https://doi.org/10.1186/s40360-025-00903-5","url":null,"abstract":"<p><strong>Background: </strong>Among the detrimental side effects caused by radiotherapy in young females is the ovarian damage, eventually causing premature ovarian failure (POF). While many signaling pathways contribute to the pathogenesis of POF, to date no sufficient data exist on the AMPK and AKT signaling pathways in irradiated ovaries. Both AMPK and AKT play crucial roles in the process of folliculogenesis. Vildagliptin (vilda) is a dipeptidyl peptidase-4 inhibitor with modulatory effect on both AMPK and AKT. Therefore, our study aimed to investigate the biochemical changes that occur in the AMPK/AKT signaling pathway, and the effect of co-administration of vildagliptin in radiation-induced POF.</p><p><strong>Methods: </strong>Female Sprague-dawley rats were randomly divided into four groups: control, radiation, radiation + vilda, or vilda alone groups. Vilda was administered orally once/day, and on the 10th day of the experiment, radiation and radiation + vilda group rats were subjected to 3.2 Gy of whole-body gamma irradiation. Behavioral activity was assessed on the 13th day of the experiment. On day 14 of the experiment, all rats were euthanized. Serum samples were collected, and ovaries were dissected for histological and biochemical analyses.</p><p><strong>Results: </strong>Irradiation of female rats resulted in increased locomotor hyperactivity, impaired memory, and ovarian damage as evidenced by the marked histopathological deterioration. Additionally, irradiation led to a significant decrease in body weight gain, gonadosomatic index, and serum estradiol level. Further, it caused a significant increase in serum AMH, phosphorylated AMPK, phosphorylated AKT, cytoplasmic Nrf2 expression and phosphorylated CREB levels. Co-administration of vilda exhibited neuroprotective effects, preserved the ovarian histological architecture but failed to preserve the primordial follicle pool in irradiated rats.</p><p><strong>Conclusion: </strong>In conclusion, AMPK/AKT signaling pathway is upregulated in radiation-induced POF. It possibly contributes to POF pathogenesis by accelerating the activation of primordial follicles, hence leading to their premature depletion. Coadministration of vilda can protect the ovaries and temporarily preserve its endocrine function; however, it does not sustain the ovarian reproductive capacity due to the early depletion of the pool of primordial follicles. Women undergoing radiotherapy should be cautious with the use of AKT-activating drugs.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"81"},"PeriodicalIF":2.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979272","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":"Safety profile of faricimab: a multi-source pharmacovigilance analysis using FAERS and JADER.","authors":"Chuanya Liu, Shangze Li, Ziyi Wang, Zhifu Li, Zhou Fang, Yuan Zhang, Yu Gao","doi":"10.1186/s40360-025-00902-6","DOIUrl":"https://doi.org/10.1186/s40360-025-00902-6","url":null,"abstract":"<p><strong>Background: </strong>Faricimab is a bispecific antibody targeting vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), offering a novel therapeutic approach for ocular diseases. However, its long-term safety profile remains under evaluation. This study analyzes its adverse events (AEs) using the U.S. FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER).</p><p><strong>Methods: </strong>AEs from FAERS (2004-2024) and JADER (2004-2024) were analyzed using disproportionality algorithms. Subgroup analyses assessed differences by age and sex. AE onset time was also assessed.</p><p><strong>Results: </strong>Several newly identified adverse events (AEs) were observed, including macular ischemia, keratic precipitates, and optic nerve injury, with strong safety signals detected in both FAERS and JADER. For instance, macular ischemia showed a high association with faricimab use (ROR = 260.46), suggesting a potential risk of retinal circulation impairment. Similarly, keratic precipitates (ROR = 739.65) indicate a notable inflammatory response. All these findings highlight the need for closer monitoring of ocular complications, particularly in high-risk patient groups. The FAERS database mainly reported retinal occlusive vasculitis, ocular vasculitis, and keratic precipitates, while JADER predominantly featured retinal occlusive vasculitis and retinal vascular occlusion. Sex-based differences indicated a higher risk of inflammatory AEs in females (e.g., uveitis and eye inflammation) and a greater incidence of retinal vascular events in males (e.g., retinal vasculitis). Age-related differences showed that older patients (≥65 years) had lower inflammatory AE risks but were more prone to optic nerve damage and retinal atrophy, while younger patients (<65 years) exhibited a higher risk of vitreous hemorrhage and cataracts.</p><p><strong>Conclusions: </strong>This study identified previously unreported safety signals, suggesting the need for potential updates to faricimab's safety labeling. Faricimab's dual-target mechanism presents unique safety concerns. Clinicians should monitor ocular inflammation and vascular complications, particularly in younger males and Asian patients. Further studies using real-world data are needed to validate these findings.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"82"},"PeriodicalIF":2.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969660","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":"Commentary on \"real world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: a meta-analysis of clinical studies\".","authors":"Ali Beheshti Namdar, Masoud Keikha","doi":"10.1186/s40360-025-00923-1","DOIUrl":"https://doi.org/10.1186/s40360-025-00923-1","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"80"},"PeriodicalIF":2.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953038","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":"Saikosaponin D inhibits the inflammatory response of secretory otitis media through FTO-mediated N⁶-methyladenosine modification of TLR4 mRNA.","authors":"Minjing Yin, Xiuli Han","doi":"10.1186/s40360-025-00910-6","DOIUrl":"https://doi.org/10.1186/s40360-025-00910-6","url":null,"abstract":"<p><p>Secretory Otitis Media (SOM) is a non-suppurative inflammatory disease of the middle ear. Saikosaponin D (SSD), a compound with significant anti-inflammatory and immunomodulatory properties, was investigated for its preventive effects and underlying mechanisms against SOM. A rat model of SOM was established through intraperitoneal ovalbumin injection. Middle ear lavage fluid (MELF) and tissue samples were collected for comprehensive analysis, including bacterial load quantification, neutrophil enumeration, and inflammatory factor assessment. HEK293T cells were utilized for mechanistic validation. Our findings demonstrated that SSD preventive treatment significantly reduced colony-forming units (CFUs) in SOM-induced rats, attenuated middle ear mucosal thickening, and suppressed pro-inflammatory cytokine levels (TNF-α, IL-6, and INF-γ). Mechanistically, SSD treatment counteracted SOM-induced m⁶A level elevation and reversed the downregulation of FTO expression. Functional studies revealed that FTO inhibition exacerbated inflammatory responses, while SSD treatment mitigated these effects. Further investigation demonstrated that SSD decreased TLR4 mRNA stability through FTO-mediated m⁶A modification. In conclusion, SSD alleviates SOM progression by reducing bacterial load and neutrophil infiltration. The therapeutic effects are mediated through FTO upregulation and subsequent m⁶A-dependent TLR4 mRNA degradation. This study elucidates a novel molecular mechanism underlying SSD's preventive action against SOM development.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"79"},"PeriodicalIF":2.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971847","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":"Comparison of the efficacy of sucroferric oxyhydroxide and lanthanum carbonate in the hyperphosphatemia of maintainable Hemodialysis.","authors":"Min Li, YiJing Kang, Chao Zhang, XiQuan Ni","doi":"10.1186/s40360-025-00914-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00914-2","url":null,"abstract":"<p><strong>Objective: </strong>To study the efficacy of sucroferric oxyhydroxide (SFOH) and lanthanum carbonate (LC) in the treatment of hemodialysis hyperphosphatemia.</p><p><strong>Methods: </strong>A total of 60 hemodialysis patients with secondary hyperparathyroidism combined with hyperphosphatemia from January 2024 to April 2024 in China Rongtong Medical & Healthcare Group Tai'an 88 Hospital were selected. All patients were randomly divided into 2 groups. One group was treated with SFOH, and the other with LC. Patients in the 2 groups were treated for 3 months continuously, and clinical outcomes, serum phosphorus, serum calcium, and intact parathyroid hormone (iPTH) levels were compared before treatment, and at 1, 2, and 3 months after treatment.</p><p><strong>Results: </strong>When compared with before treatment, the serum phosphorus levels of both groups of patients decreased significantly after 1 month, 2 months, and 3 months of treatment, with statistical significance (P < 0.01). The degree of serum phosphorus decrease in SFOH group was higher than that in LC group (P < 0.01, P < 0.05). There was no statistically significant difference in the effect of serum calcium between the two groups (P > 0.05). Both groups of patients showed a significant decrease in iPTH after treatment, with a statistically significant difference (P < 0.01). The degree of iPTH decrease in SFOH group was more pronounced than in LC group (P < 0.05). After treatment, the serum hosphorus compliance rates of SFOH group and LC Group were 80% and 53.3%, respectively, and the difference in effective rates between the two groups was statistically significant (P < 0.05).</p><p><strong>Conclusion: </strong>SFOH was superior to LC in lowering patients' blood phosphorus and iPTH levels in patients with maintenance hemodialysis hyperphosphatemia combined with secondary hyperparathyroidism.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"78"},"PeriodicalIF":2.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958229","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":"Modified diatom-based ocular suspension for sustained diclofenac sodium delivery: a novel drug carrier approach.","authors":"Ramin Ghasemishayan, Dorsa Jalaei, Faramarz Dobakhti","doi":"10.1186/s40360-025-00917-z","DOIUrl":"10.1186/s40360-025-00917-z","url":null,"abstract":"<p><strong>Purpose: </strong>Ophthalmic drugs typically last only around 15 minutes due to rapid elimination from tear flow, with only about 2% absorption, while the rest may enter the nasal mucosa, potentially causing systemic side effects. Diatoms, with properties like unique structure, abundance, low cost, heat resistance, non-toxicity, and easy access, present a promising solution for sustained drug delivery. This study aimed to prepare and evaluate an ocular suspension of diclofenac sodium loaded onto modified diatoms.</p><p><strong>Methods: </strong>Diatoms were modified with aluminum sulfate solution, followed by loading of diclofenac sodium. Characteristics of diatoms before and after modification-particle size, surface charge, and drug loading-were analyzed using electron microscopy, FTIR (Fourier Transform Infrared Spectroscopy), XRD (X-ray Diffraction), and elemental mapping. BET (Brunauer-Emmett-Teller (Surface Area Analysis) testing provided adsorption data, while DSC (Differential Scanning Calorimetry) assessed thermal properties. An in vitro release study using a dialysis bag in artificial tear fluid examined drug release over 8 hours. Drug content was determined by spectrophotometry, and cytotoxicity on MDA-MB-231 and HEP-G2 cell lines was evaluated at different diatom concentrations.</p><p><strong>Results: </strong>SEM (Scanning Electron Microscopy) imaging showed no topographic changes post-modification. BET and XRD analyses confirmed drug loading and structural stability, while FTIR indicated involvement of carboxylate groups. TGA and DSC showed stable thermal properties. Elemental mapping confirmed increased surface elements and high drug loading. Modified diatoms showed sustained drug release and no significant cytotoxicity differences.</p><p><strong>Conclusion: </strong>Modified diatoms demonstrated higher drug loading and sustained release, indicating their potential for safe and effective ocular drug delivery. Further studies are recommended to confirm these findings.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"77"},"PeriodicalIF":2.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967975","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":"Kaempferol inhibits cardiomyocyte pyroptosis via promoting O-GlcNAcylation of GSDME and improved acute myocardial infarction.","authors":"Jie Zhou, Huifei Zhou, Jianfeng Zhu, Shunjin Fang","doi":"10.1186/s40360-025-00908-0","DOIUrl":"10.1186/s40360-025-00908-0","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) is a leading fatal cardiovascular disease and poses a major threat to human health. Pyroptosis, an inflammation-related programmed cell death, plays a critical role in the progression of AMI. Kaempferol is a natural flavonoid compound with a variety of pharmacological effects, which exerts a significant cardioprotective function. The role of O-GlcNAcylation, a post-translation modification, has received attention in diseases including AMI. In this research, we explored the therapeutic potential of Kaempferol to AMI due to its well-known cardioprotective effect, including its antioxidant and anti-inflammatory properties. Hypoxia/reoxygenation (H/R) model was adopted to provoke myocardial injury and AMI mice model was established. Our findings indicated that H/R lessened cell viability and contributed to the release of LDH, IL-1β and IL-18, cell pyroptosis rate, and the expression of NLRP3, active caspase 1 and GSDMD-N-terminal domain (GSDMD-N). Kaempferol mitigated myocardial damage caused by H/R through repressing cell pyroptosis. Besides, we discovered that Kaempferol restored the levels of O-GlcNAcylation by regulating the activity of OGT (O-GlcNAc transferase) and OGA (O-GlcNAcase) in H/R-treated H9c2 cells. Notably, molecular docking revealed the binding relationship between Kaempferol and OGT. Further, we proved that knockdown of OGT abrogated the function of Kaempferol in H/R-induced pyroptosis. In AMI mice, Kaempferol relieved the myocardial tissue injury and decreased the NLRP3 and GSDME-N protein levels. More importantly, our results illustrated that OGT was responsible for the O-GlcNAcylation of GSDME at T94 site and acted as an inducing factor for GSDME phosphorylation. Namely, this study validated that Kaempferol facilitated GSDME O-GlcNAcylation to inhibit H/R-induced pyroptosis in an OGT-dependent manner.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"76"},"PeriodicalIF":2.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810433","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}