Xenobiotica最新文献_第3页

Nano-pharmacokinetics and pharmacodynamics of green-synthesized ZnO nanoparticles: a pathway to safer therapeutic applications. 绿色合成ZnO纳米颗粒的纳米药代动力学和药效学：通往更安全治疗应用的途径。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-05-21 DOI: 10.1080/00498254.2025.2505062

Aishwarya Jain, Kiran Bhise

引用次数: 0

The orexin 1-selective receptor antagonist nivasorexant is a time-dependent inhibitor of CYP2C19 and CYP3A4. 食欲素1选择性受体拮抗剂nivasorexant是一种时间依赖性的CYP2C19和CYP3A4抑制剂。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-06-08 DOI: 10.1080/00498254.2025.2513321

Alexander Treiber, Fabienne Drouet, Swen Seeland, Florian Willecke, Jodi T Williams, Hamed Aissaoui, Benjamin Berger, Stephane Delahaye

{"title":"The orexin 1-selective receptor antagonist nivasorexant is a time-dependent inhibitor of CYP2C19 and CYP3A4.","authors":"Alexander Treiber, Fabienne Drouet, Swen Seeland, Florian Willecke, Jodi T Williams, Hamed Aissaoui, Benjamin Berger, Stephane Delahaye","doi":"10.1080/00498254.2025.2513321","DOIUrl":"10.1080/00498254.2025.2513321","url":null,"abstract":"Nivasorexant was the first orexin 1-selective receptor antagonist entering into clinical development as an exploratory treatment for eating disorders.Drug-drug interactions were observed with markers of CYP2C9, CYP2C19, and CYP3A4. While the interaction with CYP2C19 was expected based on in vitro inhibition data, standard P450 inhibition screening assays according to regulatory guidelines failed to predict the interactions with CYP2C9 and CYP3A4.Mechanistic studies on the circulating metabolites of nivasorexant revealed a heterogeneous picture for the three P450 enzymes with covalent binding as a common denominator. For CYP3A4, the secondary didehydromorpholine metabolite M30 was identified as the major origin for enzyme inactivation. Epoxidation of its double bond might yield a bicyclic reactive metabolite which subsequently binds within the CYP3A4 active site.Nivasorexant and virtually all its circulating metabolites were strong competitive or time-dependent inhibitors of CYP2C19. Some of them are initially produced by CYP3A4 and only exert their inhibitory potential after diffusion into the CYP2C19 active site. CYP2C9 and CYP2C19 both produce the 6-hydroxymorpholine metabolite M25, which exists in equilibrium with its open-chain amino aldehyde form. The latter is chemically reactive and might at least in part explain the covalent binding of nivasorexant to both P450 enzymes.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"296-305"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192269","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}

引用次数: 0

Arctigenin-induced erythrocyte membrane remodelling is mediated through calcium influx, metabolic collapse, and casein kinase 1α. 牛蒡子素诱导的红细胞膜重构是通过钙内流、代谢衰竭和酪蛋白激酶1α介导的。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-06-04 DOI: 10.1080/00498254.2025.2513324

Mohammad A Alfhili, Rahaf F Alothaimeen, Jawaher Alsughayyir

{"title":"Arctigenin-induced erythrocyte membrane remodelling is mediated through calcium influx, metabolic collapse, and casein kinase 1α.","authors":"Mohammad A Alfhili, Rahaf F Alothaimeen, Jawaher Alsughayyir","doi":"10.1080/00498254.2025.2513324","DOIUrl":"10.1080/00498254.2025.2513324","url":null,"abstract":"Conclusive evidence suggests that arctigenin (AGN) holds great promise in anticancer therapy but a common and poorly understood complication of chemotherapy is anaemia which is precipitated by eryptosis and haemolysis. This study examines the cytotoxicity of AGN in RBCs.Eryptosis markers including intracellular calcium, phosphatidylserine (PS) externalisation, and cell shrinkage were detected by flow cytometry using Fluo4/AM, annexin-V-FITC, and forward light scatter, respectively. Membrane blebbing was examined using electron microscopy, and photometric and potentiometric methods were used to assay haemolytic markers including haemoglobin, potassium, AST, and LDH.AGN significantly increased Fluo4- and annexin-V-positive cells and decreased forward light scatter which was associated with membrane blebs. While PS externalisation and cell shrinkage were inhibited by extracellular calcium exclusion, suppression of haemolysis required both calcium exclusion and restriction of potassium efflux. Moreover, sucrose and mannitol rescued the cells from haemolysis while exacerbating PS externalisation, which was rather significantly blunted by guanosine and CK1α inhibitor D4476.AGN promotes calcium-dependent eryptosis through energy depletion and CK1α activation, and exhibits a potent haemolytic activity through dysregulated ion trafficking and osmotic stress. These findings underscore the hematological toxicity of AGN and identify potential inhibitors which inform future animal studies and clinical trials.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"306-316"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192268","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}

引用次数: 0

Feature-based molecular networking updates the in vitro metabolic characterisation of fenbendazole across species. 基于特征的分子网络更新了芬苯达唑跨物种的体外代谢特征。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-04 DOI: 10.1080/00498254.2025.2497047

Young-Heun Jung, Dong-Cheol Lee, Bo-Hyun Choi, Junyoung O Park, Ju-Hyun Kim

{"title":"Feature-based molecular networking updates the in vitro metabolic characterisation of fenbendazole across species.","authors":"Young-Heun Jung, Dong-Cheol Lee, Bo-Hyun Choi, Junyoung O Park, Ju-Hyun Kim","doi":"10.1080/00498254.2025.2497047","DOIUrl":"10.1080/00498254.2025.2497047","url":null,"abstract":"Feature-based molecular networking (FBMN), an advanced metabolomics tool leveraging MS/MS spectral similarity, was applied to update metabolite characterisation of fenbendazole (FBZ), a veterinary antiparasitic agent with emerging anticancer potential in humans. Despite its therapeutic promise, FBZ's human metabolic pathways remain poorly understood.In this study, FBMN was utilised for the comprehensive in vitro profiling of FBZ metabolites across species, employing high-resolution liquid chromatography-mass spectrometry (LC-HRMS) with data-dependant MS2 acquisition.Nine metabolites, including two novel sulphate-conjugated forms (M2 sulphate and M7 sulphate), were identified and structurally characterised through integrated FBMN analysis. Oxidative metabolites (M1-M4) were found to be more abundant in rat liver microsomes, whereas monkey hepatocytes exhibited higher levels of most metabolites. Notably, hydrolysed FBZ (M5) dominated human samples, accounting for the largest proportion in both liver microsomes and hepatocytes, suggesting species-specific enzymatic activity.The application of FBMN provided an enhanced, systematic approach for metabolite identification and inter-species comparison, revealing critical metabolic differences that support FBZ biotransformation. These findings offer novel insights into FBZ's metabolic pathways, supporting its safety and efficacy assessment for potential human therapeutic applications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"167-175"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050519","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}

引用次数: 0

Regulatory effect of atorvastatin combined with berberine on PI3K/AKT/FoxO1 signaling pathway in rats with hyperlipidaemia. 阿托伐他汀联合小檗碱对高脂血症大鼠PI3K/Akt/ fox01信号通路的调控作用

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-12 DOI: 10.1080/00498254.2025.2503359

Chao Yu, Weihong Yin, Jiao Li, Fan Wu, Siwen Wang, Zhaoyang Han, Haoliang Chen, Xueying Yan, Mingyu Cui

{"title":"Regulatory effect of atorvastatin combined with berberine on PI3K/AKT/FoxO1 signaling pathway in rats with hyperlipidaemia.","authors":"Chao Yu, Weihong Yin, Jiao Li, Fan Wu, Siwen Wang, Zhaoyang Han, Haoliang Chen, Xueying Yan, Mingyu Cui","doi":"10.1080/00498254.2025.2503359","DOIUrl":"10.1080/00498254.2025.2503359","url":null,"abstract":"Atorvastatin Calcium (AC) is the first line lipid-lowering drug in clinical. Nowadays, the combination of AC and BBR is often used to treat hyperlipidaemia in clinical. In order to determine the mechanism, we investigate the regulatory of atorvastatin combined with berberine on PI3K/Akt/FoxO1 signalling pathway in rats with hyperlipidaemia.The hyperlipidaemia rat model was constructed. Meanwhile, lipid-lowering and liver protective effects were determined by oil red O and H&E method. The expression of PI3K, Akt and FoxO1 was examined by IHC, WB and RT-pCR. The level of CK and LDH in serum was examined by ELISA.The results showed that the expression of PI3K, AKT increased and FoxO1 decreased in MC group compared with NC group (p < 0.01). The expression of PI3K, AKT decreased and FoxO1 increased compared with MC group (p < 0.05). The expression of FoxO1 in combination group is lower than AC group. The levels of CK and LDH in AC group increased compared with NC group (p < 0.01), but decreased significantly in AC+BBR group compared with AC group (p < 0.01).The combination of AC and BBR could regulate the lipid level by mediating PI3K/Akt/FoxO1, which is providing new references for the treatment of hyperlipidaemia.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"256-263"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050899","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}

引用次数: 0

Exploring ethanol's toxicity in the oral submucosa: chronic exposure versus abstinence in C57BL/6 mice. 探索乙醇在口腔黏膜下的毒性：C57BL/6小鼠的慢性暴露与戒断。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-25 DOI: 10.1080/00498254.2025.2505066

Devaraj Ezhilarasan, Karthik Shree Harini, Karthick Munusamy

{"title":"Exploring ethanol's toxicity in the oral submucosa: chronic exposure versus abstinence in C57BL/6 mice.","authors":"Devaraj Ezhilarasan, Karthik Shree Harini, Karthick Munusamy","doi":"10.1080/00498254.2025.2505066","DOIUrl":"10.1080/00498254.2025.2505066","url":null,"abstract":"Alcohol consumption is a recognised risk factor for the development of precancerous lesions in the oral cavity. This study investigates the effects of chronic ethanol exposure on inflammation and fibrosis in mice.Eighteen C57BL/6 mice were divided into three groups: Group I received only drinking water, while Groups II and III were exposed to 25% ethanol ad libitum for 14 weeks. Group II mice were sacrificed at the end of the 14th week, whereas Group III underwent a 4-week abstinence period before sacrifice. Gene expression related to inflammation and fibrosis, along with histopathological changes in submucosal tissue, was analysed.Chronic ethanol exposure significantly upregulated MAPK signalling markers, as well as inflammatory and fibrotic markers, in submucosal tissue. In Group III, inflammatory markers such as NF-κB, p65, NLRP3, and caspase-1 partially returned to normal levels after abstinence, whereas fibrotic markers, particularly MMP-9, remained elevated. Histopathological analysis of oral submucosa revealed epithelial atrophy and extracellular matrix accumulation in ethanol-exposed mice.These findings suggest that 14 weeks of ethanol exposure induces persistent epithelial damage, inflammation, and fibrosis in the oral submucosa, with incomplete reversal after 4 weeks of abstinence. This underscores the lasting impact of alcohol on oral tissue, even after cessation.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"209-216"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080806","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}

引用次数: 0

Prediction of the neurotoxic mechanisms of the pesticide phorate using network toxicology, molecular docking, and molecular dynamics simulation. 应用网络毒理学、分子对接、分子动力学模拟等方法预测农药膦的神经毒性机制。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-05 DOI: 10.1080/00498254.2025.2498010

Jiahui Xu, Yinghao Xiao, Jixin Li, Zhongyi Liu, Lili Zhang, Wei Xu

{"title":"Prediction of the neurotoxic mechanisms of the pesticide phorate using network toxicology, molecular docking, and molecular dynamics simulation.","authors":"Jiahui Xu, Yinghao Xiao, Jixin Li, Zhongyi Liu, Lili Zhang, Wei Xu","doi":"10.1080/00498254.2025.2498010","DOIUrl":"10.1080/00498254.2025.2498010","url":null,"abstract":"Phorate is an organophosphate pesticide that may cause neurotoxicity, although the exact mechanisms remain unclear.This study aimed to elucidate the mechanisms of neurotoxicity caused by phorate overexposure using network toxicology, molecular docking, and molecular dynamics simulation.We identified 104 potential targets and 20 core targets associated with phorate-induced neurotoxicity. Key targets, including MMP9, CASP1, and KEAP1, may be involved in neuroactive ligand-receptor interaction signalling, as well as the cAMP and calcium signalling pathways. Furthermore, molecular dynamics simulations were conducted on the KEAP1 and CASP1 protein-ligand complexes, which demonstrated the highest binding stabilities in molecular docking analysis. The binding free energies were calculated to be -27.08 and -22.80 kcal/mol for KEAP1 and CASP1, respectively, indicating that both complexes are thermodynamically stable.The methodology used in this study facilitates the identification and assessment of previously unexplored agrochemical toxicity pathways and molecular mechanisms. These findings suggest a novel approach to controlling pesticide residues and screening drugs.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"217-229"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988985","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}

引用次数: 0

Cannabidiol metabolism in vitro: the role of antiseizure medications and CYP2C19 genotypes. 大麻二酚体外代谢：抗癫痫药物和CYP2C19基因型的作用。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-10 DOI: 10.1080/00498254.2025.2498696

Nattapon Jaisupa, Michael Ashton, Sofia Birgersson

{"title":"Cannabidiol metabolism in vitro: the role of antiseizure medications and CYP2C19 genotypes.","authors":"Nattapon Jaisupa, Michael Ashton, Sofia Birgersson","doi":"10.1080/00498254.2025.2498696","DOIUrl":"10.1080/00498254.2025.2498696","url":null,"abstract":"Cannabidiol (CBD) can be used as add-on antiseizure medication. We aimed to investigate CBD depletion kinetics when combined with antiseizure medications, further the effect of intermediate-activity CYP2C19 genotype on CBD metabolism.CBD depletion in pooled human liver microsomes (HLMs) was studied at varying concentrations (400-6000 nM) in the absence and presence of valproic acid, clobazam, stiripentol and topiramate. In addition, CBD metabolism in HLMs from CYP2C19 *1/*2 or *1/*4 donors was investigated. Incubation samples were analysed for CBD and metabolites 7-OH-CBD and 7-COOH-CBD using LC-MS/MS. CBD in vitro intrinsic clearance (CLint) was calculated using estimated Vmax and Km values and further extrapolated to in vivo CLint.In vitro CLint values were reduced by approximately 25-85% in the presence of antiseizure medication(s) with the largest effect observed for the combination of four antiseizure drugs. There was no discernible difference for HLMs with CYP2C19 *1/*2 or *1/*4 genotype. Increases in CBD depletion half-lives at higher concentrations indicated substrate inhibition and/or metabolic saturation.Projected decreases in CBD CLint values when combined with several antiseizure medications suggest a potential for clinically relevant drug-drug interactions. A 1.3- to 4.8-fold increased exposure to unbound systemic CBD concentrations was predicted when combined with these antiseizure medications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"246-255"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026538","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}

引用次数: 0

Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders. NXE0041178的临床前药代动力学、代谢和处置，这是一种新型口服GPR52受体激动剂，具有治疗精神分裂症和相关精神疾病的潜力。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-19 DOI: 10.1080/00498254.2025.2501593

Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney

{"title":"Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders.","authors":"Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney","doi":"10.1080/00498254.2025.2501593","DOIUrl":"10.1080/00498254.2025.2501593","url":null,"abstract":"The physico-chemical properties, protein binding, metabolism, permeability, transporter interactions, chemical toxicity, and drug-drug interaction potential of the novel GPR52 agonist NXE0041178 were characterised.NXE0041178 demonstrated high cellular permeability, little interaction with efflux transporters P-gp and BCRP, and extensive brain exposure in rodent, consistent with its intended use in CNS disorders.In vivo pharmacokinetic profiling in mouse, rat and monkey demonstrated that NXE0041178 was well-absorbed, with low clearance, a moderate volume-of-distribution and moderate terminal half-life. Oxidative metabolism was the major elimination pathway, with negligible renal or biliary excretion.NXE0041178 displayed good in vitro-to-in vivo correlation in metabolic clearance in preclinical species and low turnover in human in vitro metabolic systems, suggestive of a human pharmacokinetic profile commensurate with once-daily dosing.Early in vitro metabolite identification studies suggested similar metabolic pathways in human and preclinical species, but a distinct metabolic profile in dog.NXE0041178 caused weak heterotropic catalytic activation of CYP3A4, and weak transcriptional induction of CYP3A4 and CYP2B6. No reactive metabolites of NXE0041178 were detected, and no genotoxicity or clinically relevant inhibition of P450 enzymes were observed.These findings extend our knowledge of the preclinical ADME profile of NXE0041178, supporting its continued development.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"151-166"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080807","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}

引用次数: 0

HSYA from safflower mitigates oxidative stress, inflammation, and apoptosis in liver ischemia-reperfusion injury. 红花HSYA减轻肝缺血再灌注损伤的氧化应激、炎症和细胞凋亡。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-22 DOI: 10.1080/00498254.2025.2507139

Jianhua Liao, Chunyan Meng, Jun Cheng, Baoqing Liu, Yuzhi Shao

{"title":"HSYA from safflower mitigates oxidative stress, inflammation, and apoptosis in liver ischemia-reperfusion injury.","authors":"Jianhua Liao, Chunyan Meng, Jun Cheng, Baoqing Liu, Yuzhi Shao","doi":"10.1080/00498254.2025.2507139","DOIUrl":"10.1080/00498254.2025.2507139","url":null,"abstract":"Liver ischemia-reperfusion injury (IRI) is a common complication during liver transplantation and surgery, characterised by oxidative stress, inflammation, and apoptosis, which contribute to hepatocyte damage and impaired liver function. Safflower, known for its antioxidant and anti-inflammatory properties, has not been fully explored for its potential to alleviate liver IRI.This study aims to investigate the effects of safflower components on oxidative stress and cell apoptosis in liver IRI. A microfluidic liver cell ischemia-reperfusion model was employed to screen safflower components for their protective effects against oxidative stress and apoptosis. The effects of HSYA and other compounds were assessed by measuring cell viability, ROS levels, apoptosis, DNA damage (8-oxo-dG), lipid peroxidation (MDA), and inflammatory cytokine production (TNF-α, IL-1β, IL-6). HSYA exhibited superior protective effects, significantly reducing ROS, apoptosis, DNA damage, and lipid peroxidation. It also decreased pro-inflammatory cytokine levels, underscoring its antioxidant and anti-inflammatory properties.These findings suggest that HSYA effectively mitigates oxidative stress, inflammation, and apoptosis in liver IRI, positioning it as a promising candidate for therapeutic liver protection.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"239-245"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102772","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}

引用次数: 0