Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Melatonin Rescues Renal Mitochondria From Multiple Stressors–Induced Oxidative Stress","authors":"Saeed Alshahrani,&nbsp;Muhammad H. Sultan,&nbsp;Hina Rashid,&nbsp;Firoz Alam,&nbsp;Andleeb Khan,&nbsp;Mohammad Suhail Akhter,&nbsp;Derayat Qamri,&nbsp;Saba Beigh,&nbsp;Farhana Riyaz","doi":"10.1111/bcpt.70031","DOIUrl":"https://doi.org/10.1111/bcpt.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>The renal system is a significant organ system vulnerable to stress due to its physiological function of toxin elimination. Exposure to a wide array of xenobiotics in humans causes deleterious effects in the kidneys. In the present study, we observed the toxic effect of a coexposure of bisphenol A and acetaminophen on the renal function and renal mitochondria of Wistar rats and its amelioration by melatonin. The animals were grouped and treated for 4 weeks as follows: (I) control; (II) melatonin; (III) bisphenol A; (IV) acetaminophen; (V) bisphenol A and acetaminophen; and (VI) bisphenol A, acetaminophen and melatonin. Coadministration of bisphenol A and acetaminophen exposure significantly impaired renal function, elevating creatinine (2.28 mg/dL), BUN (65.42 mg/dL) and uric acid (6.11 mg/dL), while increasing oxidative stress and inflammatory markers (CAT: 3.85-μmol H₂O₂/min/mg protein, GPx: 189.57-nmol NADPH/min/mg protein, GR: 96.62-nmol NADPH/min/mg protein, MnSOD: 107.24-nmol (−) epinephrine/min/mg protein, IL-6: 1750 pg/mL, TNFα: 1677 pg/mL). Melatonin coadministration improved renal markers (creatinine: 1.60 mg/dL, BUN: 45.59 mg/dL, uric acid: 4.61 mg/dL) and partially restored antioxidant defences and inflammatory markers (CAT: 5.74-μmol H₂O₂/min/mg protein, GPx: 422.74-nmol NADPH/min/mg protein, GR: 136.91-nmol NADPH/min/mg protein, MnSOD: nmol (−) epinephrine prevented from oxidation/min/mg protein, IL-6: 1677 pg/mL, TNFα: 900 pg/mL). These findings suggest that melatonin mitigates bisphenol A and acetaminophen-induced renal damage by enhancing antioxidant defences and reducing inflammation.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770288","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":"Effect of Intraoperative Dexmedetomidine on Early Attention Network Function After Gynaecological Surgery: A Randomized Controlled Study","authors":"Chen Chen,&nbsp;Yinyao Feng,&nbsp;Weixiang Tang,&nbsp;Weiwei Zhong,&nbsp;Weiwei Wu,&nbsp;Guanghong Xu,&nbsp;Hu Liu","doi":"10.1111/bcpt.70032","DOIUrl":"https://doi.org/10.1111/bcpt.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Perioperative neurocognitive disorder (PND) is a common neurological complication in patients after surgery and anaesthesia. Whether dexmedetomidine affects postoperative attention network function remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty patients aged 40–60 years underwent elective gynaecological surgery under total intravenous anaesthesia, before induction dexmedetomidine (group D) or placebo (group P) was used. The attention network test was used to assess the function of three attention networks pre- and post-operation, and blood samples were collected to test inflammatory factors and neurotransmitters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The three networks of the two groups were obviously impaired after the operation. Horizontally, on the 1st postoperative day, the degree of impairment of the alerting network in group D was less than that in group P (<i>p</i> = 0.033), and the orienting network was completely protected (<i>p</i> &lt; 0.001, vs. group P; <i>p</i> = 0.058, vs. baseline), while the executive control network improved (<i>p</i> &lt; 0.001, vs. group P; <i>p</i> = 0.045, vs. baseline). Moreover, all the inflammatory factors levels in group P increased on the 1st postoperative day. In contrast, the acetylcholine (ACh) and dopamine (DA) levels decreased significantly (<i>p</i> = 0.049 for ACh, <i>p</i> &lt; 0.001 for DA). In group D, the inflammatory factors and serum neurotransmitters showed different patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Dexmedetomidine can protect against impairment of early postoperative attention network function in middle-aged female patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Registration Number</h3>\u0000 \u0000 <p>This trial has been registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn) (ChiCTR2000031283).</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770287","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":"Role of Inflammatory and Proresolving Mediators in Endothelial Dysfunction","authors":"Ana M. Briones,&nbsp;Raquel Hernanz,&nbsp;Ana B. García-Redondo,&nbsp;Cristina Rodríguez,&nbsp;Luis M. Blanco-Colio,&nbsp;Almudena Val-Blasco,&nbsp;María J. Alonso,&nbsp;Mercedes Salaices","doi":"10.1111/bcpt.70026","DOIUrl":"https://doi.org/10.1111/bcpt.70026","url":null,"abstract":"<p>Excessive local inflammation is a common mechanism in many cardiovascular diseases (CVDs) such as hypertension, atherosclerosis and aortic aneurysms. In endothelial cells, inflammatory cytokines such as interferons, tumour necrosis factor alpha or interleukins increase oxidative stress and contractile prostanoids and the expression of adhesion molecules that reduce nitric oxide (NO) availability and bind leucocytes, thereby impairing endothelial function. Despite this evidence, anti-inflammatory therapies are not yet indicated for the treatment of most CVD. Resolution of inflammation is mediated by a family of specialized pro-resolving mediators (SPMs) that act on cognate G protein–coupled receptors to limit immune cell infiltration and initiate tissue repair. SPMs, generated from omega-3 and omega-6 polyunsaturated fatty acids, belong to four major families: lipoxins, resolvins, protectins and maresins. SPM receptors are expressed in immune and vascular cells where they regulate important processes such as phagocytosis and polarization, production of cytokines, NO and prostacyclin, and modulation of smooth muscle cell phenotype. Growing evidence in animal models demonstrates that activation of SPM receptors can protect vascular function and structure and provide beneficial effects in various CVD. We will review recent advances in the role of inflammation and SPMs in vascular (dys)function in hypertension, atherosclerosis, and aortic aneurysms.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741169","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":"Pericyte Electrical Signalling and Brain Haemodynamics","authors":"Thomas A. Longden,&nbsp;Dominic Isaacs","doi":"10.1111/bcpt.70030","DOIUrl":"https://doi.org/10.1111/bcpt.70030","url":null,"abstract":"<p>Dynamic control of membrane potential lies at the nexus of a wide spectrum of biological processes, ranging from the control of individual cell secretions to the orchestration of complex thought and behaviour. Electrical signals in all vascular cell types (smooth muscle cells, endothelial cells and pericytes) contribute to the control of haemodynamics and energy delivery across spatiotemporal scales and throughout all tissues. Here, our goal is to review and synthesize key studies of electrical signalling within the brain vasculature and integrate these with recent data illustrating an important electrical signalling role for pericytes, in doing so attempting to work towards a holistic description of blood flow control in the brain by vascular electrical signalling. We use this as a framework for generating further questions that we believe are important to pursue. Drawing parallels with electrical signal integration in the nervous system may facilitate deeper insights into how signalling is organized within the vasculature and how it controls blood flow at the network level.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741213","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":"Bruceine A Inhibits Cell Proliferation by Targeting the USP13/PARP1 Signalling Pathway in Multiple Myeloma","authors":"Mengjie Guo,&nbsp;Han Meng,&nbsp;Yi Sun,&nbsp;Lianxin Zhou,&nbsp;Tingting Hu,&nbsp;Tianyi Yu,&nbsp;Haowen Bai,&nbsp;Yuanjiao Zhang,&nbsp;Chunyan Gu,&nbsp;Ye Yang","doi":"10.1111/bcpt.70027","DOIUrl":"https://doi.org/10.1111/bcpt.70027","url":null,"abstract":"<p>Multiple myeloma (MM) is an incurable hematologic malignancy, driving significant interest in the discovery of novel therapeutic strategies. Bruceine A (BA), a tetracyclic triterpene quassinoid derived from <i>Brucea javanica</i>, has shown anticancer properties by modulating multiple intracellular signalling pathways and exhibiting various biological effects. However, the specific pharmacological mechanisms by which it combats MM remain unclear. In this study, we identified USP13 as a potential target of BA. We observed a significant increase in USP13 expression in patients with MM, which was strongly associated with a poorer prognosis. Furthermore, enhanced USP13 expression can stimulate MM cell proliferation both in vitro and in vivo. Mass spectrometry analysis, combined with co-immunoprecipitation and in vitro ubiquitination experiments, revealed PARP1 as a critical downstream target of USP13. USP13 can stabilize PARP1 protein through deubiquitination, promoting PARP1-mediated DNA damage repair (DDR) and facilitating MM progression. Notably, we utilized MM cell lines, an MM Patient-Derived Tumour Xenograft model, and a 5TMM3VT mouse model to determine the anticancer effects of BA on MM progression, revealing its potential to target USP13/PARP1 signalling and disrupt DDR in MM cells. In conclusion, these findings suggest that BA inhibiting USP13/PARP1-mediated DDR might be a promising therapeutic strategy for MM.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717213","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":"The Cells of the Vasculature: Advances in the Regulation of Vascular Tone in the Brain and Periphery","authors":"Luke S. Dunaway,&nbsp;William A. Mills III,&nbsp;Ukpong B. Eyo,&nbsp;Brant E. Isakson","doi":"10.1111/bcpt.70023","DOIUrl":"https://doi.org/10.1111/bcpt.70023","url":null,"abstract":"<p>The vasculature is a complex tissue in which multiple cell types coordinate the regulation of tissue perfusion in response to hemodynamic and biochemical signals. Advances in this field are continuing to deepen our understanding of the relative importance of these cell types through the body. In the peripheral vasculature, tone is generated primarily by smooth muscle cells and regulated by endothelial cells, and neurons. In the brain parenchyma, unique cell types including pericytes, perivascular astrocytes and microglia, also contribute to the regulation of arterial and capillary tone. Here, we provide a cell-by-cell review of the regulation of vascular tone and highlight recent advances in the regulation of vascular tone in both the periphery and cerebral vasculature.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707230","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":"The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase","authors":"Riham Rafea,&nbsp;Mauro Siragusa,&nbsp;Ingrid Fleming","doi":"10.1111/bcpt.70029","DOIUrl":"https://doi.org/10.1111/bcpt.70029","url":null,"abstract":"<p>Nitric oxide (NO) generated by the endothelial NO synthase (eNOS) plays an essential role in the maintenance of vascular homeostasis and the prevention of vascular inflammation. There are a myriad of mechanisms that regulate the activity of the enzyme that may prove to represent interesting therapeutic opportunities. In this regard, the kinases that phosphorylate the enzyme and regulate its activity in situations linked to vascular disease seem to be particularly promising. Although the actions of NO were initially linked mainly to the activation of the guanylyl cyclase and the generation of cyclic GMP in vascular smooth muscle cells and platelets, it is now clear that NO elicits the majority of its actions via its ability to modify redox-activated cysteine residues in a process referred to as <i>S</i>-nitrosylation. The more wide spread use of mass spectrometry to detect <i>S</i>-nitrosylated proteins has helped to identify just how large the NO sphere of influence is and just how many cellular processes are affected. It may be an old target, but the sheer impact of eNOS on vascular health really justifies a revaluation of therapeutic options to maintain and protect its activity in situations associated with a high risk of developing cardiovascular disease.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717170","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":"The Molecular and Clinical Impact of Atorvastatin Exposure on Paclitaxel Neurotoxicity in Sensory Neurons and Cancer Patients","authors":"Emma Simonsen,&nbsp;Christina Mortensen,&nbsp;Cathrine Lundgaard Riis,&nbsp;Karina Dahl Steffensen,&nbsp;Morten Olesen,&nbsp;Martin Thomsen Ernst,&nbsp;Tore Bjerregaard Stage,&nbsp;Anton Pottegård","doi":"10.1111/bcpt.70022","DOIUrl":"https://doi.org/10.1111/bcpt.70022","url":null,"abstract":"<p>Recent evidence suggests that atorvastatin exacerbates paclitaxel neurotoxicity via P-glycoprotein inhibition. We used a translational approach to investigate if atorvastatin or simvastatin exacerbates (i) paclitaxel neurotoxicity in human sensory neurons and (ii) paclitaxel-induced peripheral neuropathy (PIPN) in cancer patients. Paclitaxel neurotoxicity was assessed by quantifying neuronal networks of human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) with and without atorvastatin or simvastatin exposure. We estimated the odds ratio (OR) of early paclitaxel discontinuation due to PIPN in a nationwide cohort of paclitaxel-treated women (2014–2018), comparing atorvastatin users to simvastatin users and nonusers of statins. Only the highest concentration of atorvastatin (100 nM) significantly exacerbated paclitaxel neurotoxicity in iPSC-SNs (<i>p</i> &lt; 0.05). Among 576 paclitaxel-treated women, atorvastatin use was not significantly associated with early paclitaxel discontinuation due to PIPN, with adjusted ORs of 0.80 [95% confidence interval (CI) 0.34–1.88] compared with simvastatin, and 1.24 [95% CI 0.44–3.53] compared with nonuse. Supplementary analyses showed varying but statistically nonsignificant results. Our in vitro findings suggest that atorvastatin, not simvastatin, significantly worsens paclitaxel neurotoxicity. However, no link was found between atorvastatin use and early paclitaxel discontinuation due to PIPN. Larger, well-designed studies are required to clarify the discrepancy between in vitro and clinical data and the inconsistencies with previous clinical evidence.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707229","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":"The Pathobiology of Cerebrovascular Lesions in CADASIL Small Vessel Disease","authors":"Anne Joutel","doi":"10.1111/bcpt.70028","DOIUrl":"https://doi.org/10.1111/bcpt.70028","url":null,"abstract":"<p>Cerebral small vessel disease (cSVD) is a significant global health issue, accounting for approximately 25% of ischemic strokes and 20% of all dementia cases. CADASIL, the most common monogenic form of cSVD, is caused by stereotyped mutations in the NOTCH3 receptor that alter the number of cysteine residues in its extracellular domain (Notch3^ECD). The two hallmark features of CADASIL are the loss of arterial smooth muscle cells (SMCs) and the abnormal accumulation of Notch3^ECD, without associated accumulation of its transmembrane intracellular domain. Notably, cysteine-altering mutations in NOTCH3 are prevalent in the general population, and although they are not directly associated with classical CADASIL disease, they are still linked to an elevated risk of stroke and dementia. NOTCH3 is predominantly expressed in the mural cells of small blood vessels and plays an essential role in the development, maintenance, function and survival of arterial SMCs. Recent research has challenged the loss-of-function hypothesis, instead implicating Notch3^ECD aggregation, involving both mutant and wild-type NOTCH3, as the primary driver of vascular pathology in CADASIL. Consequently, therapeutic strategies targeting the reduction of Notch3^ECD levels in brain arteries, such as antisense therapies, are considered highly promising for clinical development.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707303","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":"Baicalin Ameliorates L-Glutamate-Induced Hippocampal Oxidative Stress Injury and Apoptosis in Mice by Regulating Nrf2/HO-1 Signalling Pathway","authors":"Feng Li,&nbsp;Zishan Huang,&nbsp;Huanyu Gou,&nbsp;Jiarui Zheng,&nbsp;Mingjiang Yao","doi":"10.1111/bcpt.70024","DOIUrl":"10.1111/bcpt.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the effect and mechanism of baicalin on L-glutamate-induced oxidative stress injury in the hippocampus of mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty mice were divided into five groups:Sham, model, N-acetyl-L-cysteine (NAC) and baicalin (BA-7.5 mg/kg and BA-15 mg/kg). A model of excitatory amino acid toxicity with oxidative stress injury was induced by injecting L-glutamate into the lateral ventricle. Drugs were administered intraperitoneally post-modelling. Six hours later, behavioural tests were performed. Brain lesions were observed via HE staining, and neuronal apoptosis was evaluated using TUNEL staining. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined using biochemical methods. Fluorescent staining was employed to detect the expression of reactive oxygen species (ROS). The expression of Cytochrome C (CytC) was assessed by immunohistochemistry. The levels of Nrf2, HO-1, SOD2 and catalase (Cat) were detected by qPCR and WB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The behavioural tests showed that the motion distance and pain threshold were reduced in the model group. MDA, ROS and CytC were increased, while SOD and Cat were decreased after modelling. The CA3 region of the hippocampus exhibited pathological changes, and the rate of TUNEL-positive increased. Baicalin could reverse these changes, especially BA-7.5 mg/kg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Baicalin can reduce the injury induced by L-glutamate, and the mechanism might be related to the activation of the Nrf2/HO-1 pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668967","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}