Frontiers in Pharmacology最新文献

{"title":"Erratum: Triterpenoids from <i>Ganoderma lucidum</i> inhibit cytochrome P450 enzymes interfering with the metabolic process of specific clinical drugs.","authors":"","doi":"10.3389/fphar.2024.1539089","DOIUrl":"https://doi.org/10.3389/fphar.2024.1539089","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fphar.2024.1485209.].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1539089"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin as an emerging hepatoprotective agent: current status and future perspectives.","authors":"Cheng Wang, Xiaoli Feng, Wen Li, Li Chen, Xinming Wang, Yimiao Lan, Rong Tang, Ting Jiang, Lingli Zheng, Gang Liu","doi":"10.3389/fphar.2024.1508060","DOIUrl":"10.3389/fphar.2024.1508060","url":null,"abstract":"<p><p>Apigenin (C₁₅H₁₀O₅, API) is a natural flavonoid widely found in vegetables, fruits, and plants such as celery, oranges, and chamomile. In recent years, API has attracted considerable attention as a dietary supplement due to its low toxicity, non-mutagenic properties and remarkable therapeutic efficacy in various diseases. In particular, evidence from a large number of preclinical studies suggests that API has promising effects in the prevention and treatment of a variety of liver diseases, including multifactorial liver injury, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, liver fibrosis and liver cancer. This paper provides a comprehensive review of the progress of research into the therapeutic applications of API in liver diseases as of August 2024, based on literature retrieved from databases such as Web of Science, PubMed, CNKI, Google Scholar and ScienceDirect. The hepatoprotective effects of API involve multiple molecular mechanisms, including inhibition of inflammation, alleviation of hepatic oxidative stress, amelioration of insulin resistance, promotion of fatty acid oxidation, inhibition of liver cancer cell proliferation and differentiation, and induction of tumour cell apoptosis. More importantly, signaling pathways such as Nrf2, NF-κB, PI3K/Akt/mTOR, NLRP3, Wnt/β-catenin, TGF-β1/Smad3, AMPK/SREBP, PPARα/γ, MAPKs, and Caspases are identified as key targets through which API exerts its beneficial effects in various liver diseases. Studies on its toxicity and pharmacokinetics indicate that API has low toxicity, is slowly metabolized and excreted <i>in vivo</i>, and has low oral bioavailability. In addition, the paper summarises and discusses the sources, physicochemical properties, new dosage forms, and current challenges and opportunities of API, with the aim of providing direction and rationale for the further development and clinical application of API in the food, pharmaceutical and nutraceutical fields.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1508060"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe liver injury induced by minocycline in hepatitis B patient: a Case Report.","authors":"Ran Wang, Yun Li, Xue Xia","doi":"10.3389/fphar.2024.1516217","DOIUrl":"10.3389/fphar.2024.1516217","url":null,"abstract":"<p><p>Physical liver injury is an acute and potentially serious adverse event that may result in acute liver failure or even death. Diagnosis is often challenging. Minocycline, a semi-synthetic second-generation tetracycline, has high fat solubility and good tissue permeability. It is widely used for acne treatment. This report presents a 32-year-old female hepatitis B carrier who took minocycline (50 mg twice daily) for acne. After 1 week, she experienced fatigue, jaundice, abdominal bloating, and discomfort. Upon admission, laboratory tests revealed significantly elevated transaminase levels, ascites on abdominal ultrasonography, positive hepatitis B markers, impaired coagulation function, and a final diagnosis of subacute liver failure with chronic hepatitis B. Following discontinuation of minocycline and initiation of liver enzyme protection therapy, the patient's liver and coagulation functions improved after undergoing artificial liver therapy combined with CRRT. This case highlights a rare occurrence of minocycline-induced liver injury in a hepatitis B carrier, emphasizing that acute liver injury is a potential and serious adverse effect of minocycline, particularly in patients with pre-existing liver disease.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1516217"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalpol promotes hippocampal neurogenesis and synaptogenesis in rats after multiple cerebral infarctions by mitochondrial regulation: involvement of the Shh signaling pathway.","authors":"Zishan Huang, Feng Li, Xiaoyu Zheng, Jiarui Zheng, Yilei Dong, Zhao Ding, Huanyu Gou, Mingjiang Yao, Jianxun Liu","doi":"10.3389/fphar.2024.1461279","DOIUrl":"10.3389/fphar.2024.1461279","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke greatly threatens human life and health. Neuro-restoration is considered to be the critical points in reestablishing neurological function and improving the quality of life of patients. Catalpol is the main active ingredient of the Chinese herbal medicine <i>Dihuang</i>, which has the beneficial efficacy in traditional remedy, is closely related to the mitochondrial morphology and function. In the present study, we investigated whether catalpol has a neurorestorative effect after multiple cerebral infarctions and its underlying mechanisms.</p><p><strong>Methods: </strong>In this study, male 8-week-old Sprague-Dawley (SD) rats were grouped according to neurological deficit scores to minimize differences between groups the second day: sham group, model group, Ginkgo biloba P.E (EGb) (Ginaton:18 mg/kg) group, model + CAT 30 mg/kg group (CAT 30), model + CAT 60 mg/kg group (CAT 60), and model + CAT 120 mg/kg group (CAT 120). From the first day to the fourteenth day after MCI, rats were given the corresponding doses of drugs by gastric administration every day(1 mL/100g), and from day 7 to day 14, all rats were injected with Brdu solution (50 mg/kg) i.p. Neuro-Function was assessed by the neurologic deficit scores. Then we observed measurement of brain atrophy and fluorescent Nissl staining. The expression of BrdU+/DCX+ cells and the BDNF concentrations were tested to observe the neuro-restoration effect. Transmission electron microscope (TEM) and Western blot (WB) were used to observed synaptogenesis. we observed the restoration of mitochondrial function by detecting the intracortical calcium and T-AOC content. Finally, we examined the protein and mRNA expression of shh signaling pathway through q-PCR and WB.</p><p><strong>Results: </strong>Catalpol alleviated neurological deficits, reduced the degree of brain atrophy, as well as minimize pathological damage in the hippocampus and cortex. In addition, catalpol also promoted hippocampal neurogenesis and synaptogenesis by improving the mitochondrial structure and promoting mitochondrial function, as evidenced by the up-regulation of positive expression of both Recombinant Doublecortin (DCX) and 5-Bromodeoxyuridinc (BrdU), the enhancement of the Total antioxidant capacity (T-AOC), and the increase in the expression of synapse-associated proteins, Synaptophysin (SYP) and post-synaptic density-95 (PSD-95). Finally, we observed that catalpol up-regulated the expression of Sonic hedgehog (Shh) and Glioma-associated homologue-1 (GLI-1), factors related to the Shh signaling pathway.</p><p><strong>Discussion: </strong>In conclusion, catalpol may regulate mitochondria through activation of the Shh signaling pathway and exert its role in promoting hippocampal neurogenesis and synaptogenesis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1461279"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCA1 promote tumor environment heterogeneity via epithelial mesenchymal transition in Huh7 and HepG2 liver cancer cell.","authors":"Dinglai Yu, Fang Guo, Qiyu Zhang, Huajun Yu, Wenmin Wang, Yunzhi Chen","doi":"10.3389/fphar.2024.1498528","DOIUrl":"10.3389/fphar.2024.1498528","url":null,"abstract":"<p><p>In this study, we delve into the intrinsic mechanisms of cell communication in hepatocellular carcinoma (HCC). Initially, employing single-cell sequencing, we analyze multiple malignant cell subpopulations and cancer-associated fibroblast (CAF) subpopulations, revealing their interplay through receptor-ligand interactions, with a particular focus on SPP1. Subsequently, employing unsupervised clustering analysis, we delineate two clusters, C1 and C2, and compare their infiltration characteristics using various tools and metrics, uncovering heightened cytotoxicity and overall invasion abundance in C1. Furthermore, our gene risk scoring model indicates heightened activity of the immune therapeutic pathway in C1. Lastly, employing a formulated scoring system, we stratify patients into high and low-risk groups, revealing notably poorer outcomes in the high-risk cohort on Kaplan-Meier curves. Risk scores exhibit a negative correlation with model genes and immune cell infiltration scores, indicating poor prognosis in the high-risk group. Further characterization elucidates the regulatory landscape of the high and low-risk groups across various signaling pathways. In addition, we used wet lab experiments to prove that ABCA1 plays a pro-oncogenic role in hepatocellular carcinoma cells by promoting proliferation, invasion, migration, and reducing apoptosis. In summary, these findings provide crucial insights, offering valuable clues and references for understanding HCC pathogenesis and patient prognosis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1498528"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, bioavailability, and tissue distribution of MRTX1133 in rats using UHPLC-MS/MS.","authors":"Wei Lu, Rong Zeng, Meng Pan, Yuan Zhou, Huijuan Tang, Wanying Shen, Yijun Tang, Pan Lei","doi":"10.3389/fphar.2024.1509319","DOIUrl":"10.3389/fphar.2024.1509319","url":null,"abstract":"<p><strong>Introduction: </strong>MRTX1133 is a selective and reversible small molecule inhibitor of KRAS (G12D), which significantly delays the progression of solid tumors. However, no study on the absorption, distribution, and excretion of MRTX1133.</p><p><strong>Methods: </strong>A fast ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry method was developed for the determination of MRTX1133 in rat plasma, tissue homogenate, and urine. The method applied to the pharmacokinetics, bioavailability, tissue distribution, and excretion of MRTX1133 after oral administration (25 mg/kg) and intravenous administration (5 mg/kg).</p><p><strong>Results: </strong>The calibration curve for MRTX1133 in plasma and other homogenates was linear, with <i>r</i> ² > 0.99. The intra- and inter-day accuracies were ranged from 85% to 115% and precision were within ± 10%. The matrix effect and recovery were within ± 15 %. The Cmax of MRTX1133 was 129.90 ± 25.23 ng/mL at 45 min after oral administration. The plasma half-life (t_1/2) of MRTX1133 was 1.12 ± 0.46 h after oral administration and 2.88 ± 1.08 after intravenous administration. Its bioavailability was 2.92%. Furthermore, MRTX1133 was widely distributed in all the main organs, including liver, kidney, lung, spleen, heart, pancreas, and intestine. MRTX1133 was still detectable in liver, kidney, lung, spleen, heart, and pancreas after 24 h. The excretion ratio of prototype MRTX1133 through kidney was 22.59% ± 3.22% after 24 h.</p><p><strong>Conclusions: </strong>MRTX1133 was quickly absorbed, and widely distributed in the main organs. This study provided a reference for the quantitative determination of MTRX1133 in preclinical or clinical trials.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1509319"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex.","authors":"Yongmei Feng, Stefan Grotegut, Predrag Jovanovic, Valentina Gandin, Steven H Olson, Rabi Murad, Anne Beall, Sharon Colayco, Paul De-Jesus, Sumit Chanda, Brian P English, Robert H Singer, Michael Jackson, Ivan Topisirovic, Ze'ev A Ronai","doi":"10.3389/fphar.2024.1528449","DOIUrl":"https://doi.org/10.3389/fphar.2024.1528449","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fphar.2022.1029093.].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1528449"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clade Ib: a new emerging threat in the Mpox outbreak.","authors":"Shriyansh Srivastava, Laxmi, Khyati Sharma, Sathvik Belagodu Sridhar, Sirajunisa Talath, Javedh Shareef, Rachana Mehta, Prakisini Satapathy, Ranjit Sah","doi":"10.3389/fphar.2024.1504154","DOIUrl":"10.3389/fphar.2024.1504154","url":null,"abstract":"<p><p>Monkeypox, a zoonotic virus in the <i>Orthopoxvirus genus</i>, has drawn global attention for its impact on public health. In the current Mpox outbreak, a novel clade, Ib, has emerged as a significant and potentially fatal threat. This review examines the dynamics of MPXV transmission, person-to-person spread, and infection mechanisms, highlighting key risk factors. We explore the clinical features of Mpox, focusing on symptomology, illness duration, and the distinguishing characteristics of clade Ib compared to other clades. A critical analysis addresses diagnostic techniques and emphasizes the need for robust surveillance, particularly for clade Ib detection. We review recent prevention and treatment strategies, including antiviral drugs and vaccines, with a focus on clade Ib containment. The conclusion underscores the urgency of global collaboration to prevent and prepare for emerging threats like clade Ib and identifies crucial research paths and knowledge gaps. This review offers a comprehensive overview of clade Ib, covering its emergence, genetic traits, epidemiological impact, transmission patterns, clinical features, the role of Artificial Intelligence (AI) in outbreak management, detection challenges, and implications for public health response.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1504154"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 composition, immunological activity and anti-fatigue effects of different parts in sika deer antler.","authors":"Siqi Chen, Yidan Li, Yichun Yang, Shibo Zhao, Huali Shi, Chengkai Yang, Min Wu, Aiwu Zhang","doi":"10.3389/fphar.2024.1468237","DOIUrl":"10.3389/fphar.2024.1468237","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sika deer (&lt;i&gt;Cervus nippon Temminck&lt;/i&gt;, 1838) antler is a highly esteemed tonic renowned for its abundant assortment of polypeptides, polysaccharides, amino acids, and minerals, and is recognized for its multifarious pharmacological properties. However, limited research has been conducted regarding the variation in composition of deer antlers between the upper and basal sections, as well as their pharmacological effects on immunological activity and anti-fatigue in mice. The objective of this study was to conduct a comprehensive analysis on the appearance, chemical composition, and pharmacological effects of different components within sika deer antlers. This investigation aims to elucidate the disparities in quality among various parts of antlers and establish a theoretical foundation for the precise utilization of sika deer antlers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The contents of protein, amino acids, polysaccharides, phospholipids, minerals and nucleotides in wax, powder, gauze and bone slices were determined by different nutrient assays. Then, 100 mice were randomly divided into 5 groups. The mice in control group were administered 0.3 mL of saline solution per day. The mice in experimental groups were administered 0.3 mL enzymatic hydrolysate of the wax slice, powder slice, gauze slice, bone slice separately per day, continuously for 14 days from the first day. The effect of antler on boosting immunity was evaluated by testing organ indices and assessing immunoglobulin levels by ELISA. Anti-fatigue effects were assessed by a mouse swimming test. Finally, the correlation between composition and pharmacological effects was analysed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The content of each marker substance gradually decreases from the upper to the basal of deer antler. The protein and uracil content in the wax slice were significantly higher than the other three groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), and the phospholipid and inosine content were strongly significantly higher than the other three groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). The content of polysaccharides and hypoxanthine in the wax slice group and powder slice group was significantly higher than that in the gauze slice group and bone slice group (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). The amino acid content decreases from the upper to the basal section. Among, the content of Glu, Gly, His, and Pro wax slice was significantly higher than the other three groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). The content of other minerals except Fe and Mg in the wax slice group was significantly higher than the other three groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), and the content of Fe and Mg in the bone slice was the highest. Additionally, the immune organ index, immunoglobulin, and glycogen contents displayed a significant increase in comparison to both the control group and the other experimental groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). And the swimming endurance of mice in the wax slice group was significantly prolonged (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). The skeletal muscle s","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1468237"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive iron overload in middle-aged mice impairs olfactory function, triggers lipid oxidation and induces apoptosis.","authors":"Lin Deng, Qihui Luo, Yucong Liu, Yao Wang, Zongliang Xiong, Hongping Wang, Lu Zhao, Lanlan Jia, Riyi Shi, Chao Huang, Zhengli Chen","doi":"10.3389/fphar.2024.1506944","DOIUrl":"10.3389/fphar.2024.1506944","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to investigate the progressive impact of chronic iron overload on the olfactory bulb, a region significantly affected in early neurodegenerative diseases like Parkinson's and Alzheimer's. The focus is on understanding how iron accumulation leads to oxidative stress, mitochondrial dysfunction, and neuronal damage over time in middle-aged mice.</p><p><strong>Method: </strong>The mice were continuously administered FC for a duration of 16 weeks, and the olfactory behavior of the mice was observed at intervals of 4 weeks. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to detect alterations in iron content within the olfactory bulb of the mice, while levels of lipid peroxidation and antioxidant indexes were assessed using biochemical kits. Additionally, western blotting and qPCR techniques were utilized to analyze transcriptional and expression changes in proteins and genes related to iron metabolism. Furthermore, microstructural modifications as well as mitochondrial observations were conducted through paraffin sectioning and transmission electron microscopy (TEM).</p><p><strong>Result: </strong>A significant and progressive increase in iron accumulation in the olfactory bulb, starting from week 8 and peaking at week 16. This accumulation coincided with a decline in olfactory function observed at week 12. Key markers of oxidative stress, such as 4-HNE and MDA, were elevated in specific layers, and antioxidant defenses were reduced. Mitochondrial damage became evident from week 8, with caspase-3 activation indicating increased apoptosis, particularly in the granular layer. This study is to demonstrate the link between chronic iron overload and progressive olfactory dysfunction in the context of neurodegenerative diseases. It provides evidence that iron-induced oxidative stress and mitochondrial damage in the olfactory bulb contribute to early sensory deficits, suggesting that the olfactory bulb's selective vulnerability can serve as an early biomarker for neurodegenerative conditions.</p><p><strong>Conclusion: </strong>Chronic iron overload leads to progressive oxidative damage, mitochondrial dysfunction, and apoptosis in the olfactory bulb, causing sensory deficits. Targeting iron accumulation and oxidative damage may offer new strategies for early intervention in neurodegenerative diseases, highlighting the importance of addressing iron dysregulation.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1506944"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}