Xenobiotica最新文献_第4页

Berberine hydrochloride induces apoptosis in triple-negative breast cancer cells through modulation of the sirtuin/p65 signalling axis. 盐酸小檗碱通过调节sirtuin/p65信号轴诱导三阴性乳腺癌细胞凋亡

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-08-01 Epub Date: 2026-07-12 DOI: 10.1080/00498254.2026.2697209

Zhimin Zhao, Shu Xu, Yushi Yang, Ling Feng, Kaixuan Liu, Jinjin Huang, Tian Qin, Fan Yang

{"title":"Berberine hydrochloride induces apoptosis in triple-negative breast cancer cells through modulation of the sirtuin/p65 signalling axis.","authors":"Zhimin Zhao, Shu Xu, Yushi Yang, Ling Feng, Kaixuan Liu, Jinjin Huang, Tian Qin, Fan Yang","doi":"10.1080/00498254.2026.2697209","DOIUrl":"10.1080/00498254.2026.2697209","url":null,"abstract":"1. Triple-negative breast cancer (TNBC) is a highly aggressive subtype with few available therapeutic strategies. Berberine Hydrochloride (BBR) has shown anticancer potential but its mechanisms in TNBC remain unclear.2. We used cell viability assays, immunohistochemistry, western blotting, and metabolic assays to investigate the effects of BBR on TNBC cells.3. BBR markedly reduced the viability of TNBC cell lines and increased apoptosis compared with untreated controls. Relative to adjacent non-tumor tissues, TNBC tumor samples showed higher levels of total p65, p65 K310 acetylation, and p65 S536 phosphorylation; the same pattern appeared in TNBC cell lines compared with normal breast epithelial cells. In TNBC cells, both BBR and NAM increased p65 K310 acetylation while reducing S536 phosphorylation relative to vehicle treatment. SIRT2 expression was elevated in TNBC tumors and cell lines compared with their controls, whereas BBR decreased SIRT2 levels. BBR also induced stronger oxidative stress than controls and caused mitochondrial dysfunction, including membrane potential loss and reduced oxygen consumption and acidification rates.4. BBR induces apoptosis in TNBC cells and is associated with p65 acetylation/phosphorylation changes, SIRT2 downregulation, and mitochondrial dysfunction. This study provides a novel mechanistic basis for BBR as a potential therapeutic agent for TNBC.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"672-685"},"PeriodicalIF":1.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353859","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

Evaluation of the effects of paeoniflorin on cytochrome P450 isozymes in rats. 芍药苷对大鼠细胞色素P450同工酶的影响。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-08-01 Epub Date: 2026-07-12 DOI: 10.1080/00498254.2026.2699831

Jia-Ou Chen, Ling-Li Zhou, Jian-Heng Lin, Hao-Tian Zhou, Lai-Fang Sun, Cheng-Ke Huang

{"title":"Evaluation of the effects of paeoniflorin on cytochrome P450 isozymes in rats.","authors":"Jia-Ou Chen, Ling-Li Zhou, Jian-Heng Lin, Hao-Tian Zhou, Lai-Fang Sun, Cheng-Ke Huang","doi":"10.1080/00498254.2026.2699831","DOIUrl":"10.1080/00498254.2026.2699831","url":null,"abstract":"1. This study aims to investigate the effects of orally administered paeoniflorin (PF), a major bioactive compound from Paeonia lactiflora, on cytochrome P450 (CYP450) enzyme activity in rats to assess potential drug-drug interactions (DDIs). Following PF treatment, rats received a mixed probe drug solution containing phenacetin (PHE), tolbutamide (TOL), omeprazole, and metoprolol, and plasma concentrations of the substrates and metabolites were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. The metabolic ratio, calculated as the ratio of metabolite to parent drug area under the curve (AUC), was used to evaluate CYP activity.2. Results showed that AUCAcetaminophen/AUCPHE values were significantly elevated in PF-treated groups, indicating induction of CYP1A2, whereas AUCOHTOL/AUCTOL values were significantly reduced, suggesting inhibition of CYP2C11. No significant effects were observed on CYP2C or CYP2D2 activities.3. These findings indicate that PF can modulate CYP1A2 and CYP2C11 activities under the experimental conditions tested, as assessed using PHE and TOL as functional markers. However, the magnitude of these effects was modest and observed only at relatively high PF doses (50 and 100 mg/kg). Given the inherent species differences between rat and human CYP enzymes, direct extrapolation of these findings to human CYP1A2 and CYP2C11 requires further validation in human-relevant models.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"641-648"},"PeriodicalIF":1.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388124","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

Acute aluminum phosphide poisoning: evolving perspectives on toxic mechanisms and evidence-based clinical management. 急性磷化铝中毒：毒性机制和循证临床管理的演变观点。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-08-01 Epub Date: 2026-07-19 DOI: 10.1080/00498254.2026.2704049

Saeed Aghebat-Bekheir, Amir Baghaei, Armin Salek Maghsoudi, Hamed Haghi-Aminjan, Mahban Rahimifard, Somayyeh Karami-Mohajeri, Mohammad Amin Rezvanfar, Maryam Akhgari, Mohammad Abdollahi

{"title":"Acute aluminum phosphide poisoning: evolving perspectives on toxic mechanisms and evidence-based clinical management.","authors":"Saeed Aghebat-Bekheir, Amir Baghaei, Armin Salek Maghsoudi, Hamed Haghi-Aminjan, Mahban Rahimifard, Somayyeh Karami-Mohajeri, Mohammad Amin Rezvanfar, Maryam Akhgari, Mohammad Abdollahi","doi":"10.1080/00498254.2026.2704049","DOIUrl":"10.1080/00498254.2026.2704049","url":null,"abstract":"Aluminium phosphide (AlP) is a chemical compound that is used as a pesticide for suicidal purposes and can cause death, and it poses a challenge to health in some countries. AlP in the presence of stomach acid leads to the release of phosphine, which inhibits mitochondrial function and reduces ATP levels. This poisoning has devastating effects on the front line of damage on the cardiovascular and gastrointestinal systems, causing symptoms such as vomiting, cardiac arrhythmias, and heart failure.A focused search was performed utilising the terms 'aluminium phosphide,' 'phosphine,' 'antidote,' 'case report,' and 'treatment' within the scientific databases Scopus, Web of Science, and PubMed. Studies have shown that supportive treatment, decontamination, and antioxidant therapy can help reduce toxic effects.Many studies have been conducted in vitro and in clinical models to identify specific antidotes, providing valuable insight into the management of poisoning. Given the lack of a particular antidote, new therapeutic approaches offer promising solutions for managing this poisoning.New knowledge, including artificial intelligence, can help prevent and manage diseases and treatments. However, further efforts are needed to develop more effective treatments and prevent the misuse of this substance.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"686-698"},"PeriodicalIF":1.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449541","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

Intestinal deglycosylation activates saikosaponins as potent, selective UGT2B7/2B15 inhibitors: structural basis and implications for herb-drug interactions. 肠道去糖基化激活柴草皂苷作为有效的，选择性的UGT2B7/2B15抑制剂：结构基础和草药相互作用的意义。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-08-01 Epub Date: 2026-06-29 DOI: 10.1080/00498254.2026.2692510

Jinqian Chen, Peiyao Duan, Haotian Ma, Aina Liu, Yan Dong, Lu Sun, Xichuan Li, Zhenyu Zhao

{"title":"Intestinal deglycosylation activates saikosaponins as potent, selective UGT2B7/2B15 inhibitors: structural basis and implications for herb-drug interactions.","authors":"Jinqian Chen, Peiyao Duan, Haotian Ma, Aina Liu, Yan Dong, Lu Sun, Xichuan Li, Zhenyu Zhao","doi":"10.1080/00498254.2026.2692510","DOIUrl":"10.1080/00498254.2026.2692510","url":null,"abstract":"Radix Bupleuri (RB)-induced hepatotoxicity and herb-drug interactions have raised clinical concerns, yet the role of its intestinal metabolites, saikogenins (SGs), in modulating human UDP-glucuronosyltransferase (UGT) activity remains poorly understood.Using 11 recombinant human UGT isoforms and 4-methylumbelliferone as the probe substrate, we demonstrate that the parent saikosaponins (SSA, SSC, SSD) produced no potent, isoform-selective inhibition of any of the tested UGT isoforms at 100 μM, whereas the deglycosylated aglycones SGA and SGD selectively and potently inhibited UGT2B7 and UGT2B15 (IC50: 0.24-1.88 μM; Ki: 0.14-1.34 μM) through competitive mechanisms.Molecular docking revealed that deglycosylation removes steric hindrance from the sugar moiety, enabling the aglycone backbone to penetrate the catalytic pocket, where the most potent metabolite SGD anchored the conserved catalytic histidine of UGT2B7 (HIS481); inhibition of UGT2B15 instead arose from deep occupancy of the hydrophobic pocket.In vitro-in vivo extrapolation yielded an R-value of 1.36 for SGD-UGT2B7, exceeding the regulatory threshold (R ≥ 1.1), indicating a clinically significant risk when RB preparations are co-administered with narrow-therapeutic-index UGT2B7 substrates such as morphine or zidovudine.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"699-707"},"PeriodicalIF":1.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284550","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

Total saponins from ginseng stems and leaves antagonise acute lead-cadmium co-exposure-induced oxidative liver damage in mice via the Keap1/Nrf2 signalling pathway. 人参茎叶总皂苷通过Keap1/Nrf2信号通路拮抗急性铅镉共暴露诱导的小鼠氧化性肝损伤

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-07-01 Epub Date: 2026-06-25 DOI: 10.1080/00498254.2026.2693909

Bo Yan, Yang Wang, Yixin Xu, Qiangying Zhang, Yuewan Pu, Yinbo Gui, Xiaorong Zhang, Yutong Jiang, Wei Zhang, Gang Shu

{"title":"Total saponins from ginseng stems and leaves antagonise acute lead-cadmium co-exposure-induced oxidative liver damage in mice via the Keap1/Nrf2 signalling pathway.","authors":"Bo Yan, Yang Wang, Yixin Xu, Qiangying Zhang, Yuewan Pu, Yinbo Gui, Xiaorong Zhang, Yutong Jiang, Wei Zhang, Gang Shu","doi":"10.1080/00498254.2026.2693909","DOIUrl":"10.1080/00498254.2026.2693909","url":null,"abstract":"1. Lead (Pb) and cadmium (Cd) induce liver damage mainly via oxidative stress. Total saponins from ginseng stems and leaves (TSGSL) possess antioxidant properties, but their protective effect against Pb-Cd co-exposure remains unclear.2. This study aimed to investigate the hepatoprotective effect and mechanism of TSGSL in acute Pb-Cd co-exposed mice.3. Male KM mice received TSGSL (30 or 60 mg/kg, orally) once daily for 14 days, then a single acute exposure to Pb (150 mg/kg) and Cd (15 mg/kg). Liver function, oxidative stress markers, histopathology, pro-inflammatory cytokines, and Keap1/Nrf2 pathway gene mRNA were assessed.4. TSGSL dose-dependently alleviated Pb-Cd-induced liver injury. At 60 mg/kg, it reduced ALT by 46.0% and AST by 43.3%, decreased hepatic MDA by 50.0%, increased hepatic T-SOD, CAT and GSH-PX by 36.9%, 69.5% and 36.7%, respectively, and lowered pro-inflammatory cytokines (e.g. TNF-α by 51.7% and IL-1β by 46.0%). Histopathological damage was ameliorated. TSGSL upregulated mRNA expression of Keap1/Nrf2-related genes. The 30 mg/kg dose showed weaker effects.5. TSGSL protects against acute Pb-Cd-induced oxidative liver damage in mice, potentially via transcriptional upregulation of the Keap1/Nrf2 pathway and enhancement of antioxidant capacity. Further studies are needed to investigate chronic Pb-Cd co-exposure and gut microbiota involvement.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"620-632"},"PeriodicalIF":1.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303236","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

Pharmacokinetics, mass balance and metabolic profiling of resmetirom in healthy subjects and nonclinical metabolism and disposition. 雷司美康在健康人群中的药代动力学、质量平衡和代谢特征以及非临床代谢和处置。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-07-01 Epub Date: 2026-06-22 DOI: 10.1080/00498254.2026.2687126

James K Hennan, Raul C Camacho, Eric Solon, Brian Schmidt, Kevin French, Edward Chiang, Rebecca Taub

{"title":"Pharmacokinetics, mass balance and metabolic profiling of resmetirom in healthy subjects and nonclinical metabolism and disposition.","authors":"James K Hennan, Raul C Camacho, Eric Solon, Brian Schmidt, Kevin French, Edward Chiang, Rebecca Taub","doi":"10.1080/00498254.2026.2687126","DOIUrl":"10.1080/00498254.2026.2687126","url":null,"abstract":"Resmetirom is a liver-directed, thyroid hormone receptor-β (THR-β)-selective agonist approved for the treatment of adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced liver fibrosis. Disposition in rats and dogs was qualitatively similar to that observed in humans, with high concentrations observed in the liver, kidney, and caecum. The primary circulating metabolite, MGL-3623 (M1), was disproportionate in humans and formed predominantly via CYP2C8. Resmetirom exhibited >99% plasma protein binding in all species and was a substrate for BCRP, OSTα/β, OATP1B1/B3, and, to a lesser extent, MDR1.A [14C]resmetirom mass balance study in healthy men pre-dosed with 100 mg/d resmetirom (steady-state) demonstrated plasma pharmacokinetics of total radioactivity aligned with unlabelled resmetirom and MGL-3623, with Cmax reached within 3-4 h. Radioactivity was largely confined to plasma vs whole blood, with parent compound the predominant radiolabelled species and MGL-3623 the major metabolite. Total recovery was 91.0% (excretion: 67.4% faecal, 23.6% urinary); in excreta, resmetirom was a minor component and no single metabolite exceeded 10% of the dose. Resmetirom inhibited CYP2C8 and weakly induced CYP2B6 and CYP3A4 in vitro.These findings demonstrate the consistent metabolic profile and favourable hepatic disposition of resmetirom across species, supporting its pharmacokinetic properties in humans for the treatment of MASH.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"563-575"},"PeriodicalIF":1.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212933","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

Evaluation of drug-drug interactions of traditional Japanese medicines (Hochuekkito, Goreisan, and Ninjin'yoeito) in CYP3A-humanised mice. cyp3a人源化小鼠对日本传统药物（Hochuekkito， Goreisan和Ninjin'yoeito）的药物相互作用的评价。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-07-01 Epub Date: 2026-06-21 DOI: 10.1080/00498254.2026.2687119

Mari Hida, Chiharu Sadakane, Mitsue Nishiyama, Akinori Nishi, Genki Minegishi, Satoshi Abe, Kanako Kazuki, Yasuhiro Kazuki, Kaoru Kobayashi

{"title":"Evaluation of drug-drug interactions of traditional Japanese medicines (Hochuekkito, Goreisan, and Ninjin'yoeito) in CYP3A-humanised mice.","authors":"Mari Hida, Chiharu Sadakane, Mitsue Nishiyama, Akinori Nishi, Genki Minegishi, Satoshi Abe, Kanako Kazuki, Yasuhiro Kazuki, Kaoru Kobayashi","doi":"10.1080/00498254.2026.2687119","DOIUrl":"10.1080/00498254.2026.2687119","url":null,"abstract":"1. Traditional Japanese medicines (Kampo medicines) are increasingly used concurrently with other medications, but evidence regarding their potential for drug-drug interactions (DDIs) is insufficient. Given the important role of cytochrome P450 3 A (CYP3A) in DDIs, this study assessed the CYP3A-mediated DDI risk of three Kampo medicines (Hochuekkito, Goreisan, and Ninjin'yoeito).2. We utilised a CYP3A-humanised mouse model to comprehensively evaluate the effects of the three Kampo medicines on CYP3A activity, including an analysis of the area under the plasma concentration-time curve (AUC) and AUC ratio (AUCR).3. None of the three Kampo medicines tested significantly affected the AUC of the CYP3A substrate triazolam or the AUCRs of triazolam metabolites.4. These results provide important preclinical evidence indicating the lack of a significant net effect on CYP3A-mediated DDIs for Hochuekkito, Goreisan, and Ninjin'yoeito under the tested repeated-dosing conditions, thereby supporting their safe and proper use.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"633-639"},"PeriodicalIF":1.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212963","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

Detection of hard electrophilic reactive metabolites formed from alicyclic amines using glutathione trapping. 利用谷胱甘肽诱捕法检测脂环胺形成的硬亲电反应性代谢物。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-07-01 Epub Date: 2026-06-29 DOI: 10.1080/00498254.2026.2682894

Xiusheng Miao, Gordon Dear, Kevin Colizza, John Barrett, Simon Nicolle, Huw Lewis

{"title":"Detection of hard electrophilic reactive metabolites formed from alicyclic amines using glutathione trapping.","authors":"Xiusheng Miao, Gordon Dear, Kevin Colizza, John Barrett, Simon Nicolle, Huw Lewis","doi":"10.1080/00498254.2026.2682894","DOIUrl":"10.1080/00498254.2026.2682894","url":null,"abstract":"Alicyclic amines are ubiquitous compounds with manifold uses in medicinal chemistry. Unfortunately, they are subject to metabolic activation to form reactive intermediates. Alicyclic amines were observed to form direct cysteine (Cys) or cysteinylglycine (CysGly) conjugates across a large GSK GSH trapping dataset. These results suggest that hard electrophilic intermediates were generated from the alicyclic amines (e.g. piperidine) and trapped as Cys and/or CysGly conjugates. This is unusual since there is a general consensus that alicyclic amine biotransformation forms hard electrophiles typically require hard nucleophile trapping agents and cannot be trapped by soft nucleophiles.Compound A and tofacitinib, both containing a piperidine group, were used as alicyclic amine examples to explore the bioactivation pathways generating hard electrophiles in GSH trapping studies. Direct Cys and CysGly conjugates on the piperidine ring were observed for Compound A and tofacitinib in GSH trapping experiments. Both were proposed to be the thioethers resulting from reactions with hard electrophile iminium intermediates. Aldehyde intermediates formed through piperidine ring-opening were also captured by Cys and CysGly. Therefore, the aforementioned hard electrophiles created through bioactivation of alicyclic amines can be screened in drug discovery GSH trapping studies.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"583-593"},"PeriodicalIF":1.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144716","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

Modulatory role of fucoidan against monosodium glutamate-induced reproductive and hepatorenal toxicity in adult male rats. 岩藻聚糖对味精诱导的成年雄性大鼠生殖和肝肾毒性的调节作用。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-07-01 Epub Date: 2026-06-17 DOI: 10.1080/00498254.2026.2683640

Qurat Ul Ain, Mehwish David, Seemab Younas, Ayesha Batool, Moazama Batool, Fatima Talib

{"title":"Modulatory role of fucoidan against monosodium glutamate-induced reproductive and hepatorenal toxicity in adult male rats.","authors":"Qurat Ul Ain, Mehwish David, Seemab Younas, Ayesha Batool, Moazama Batool, Fatima Talib","doi":"10.1080/00498254.2026.2683640","DOIUrl":"10.1080/00498254.2026.2683640","url":null,"abstract":"The present study aims to analyse the curative efficacy of fucoidan on MSG mediated changes in hepatorenal and reproductive organs.For this, 42 adult male rats were grouped into six (N = 7animals/group), and treated for 30 consecutive days with following dose regime: Control (saline water), MSG (60 mg/kg), Fucoidan-low-dose (FLD 100 mg/kg), Fucoidan-high-dose (FHD 200 mg/kg), MSG+FLD (60 mg/kg + 100mg/kg) and MSG+FHD (60 mg/kg + 200mg/kg). On day 31, animals were sacrificed, organs were collected, and subjected to sperm parameters, antioxidant enzyme activities, DNA damage and histomorphometric analysis.The findings showed that MSG caused significant decline in sperm parameters and antioxidant enzymes activity, while increasing the concentrations of oxidative stress markers. MSG administration also showed significant DNA damage in sperm, liver and kidney cells. Additionally, adverse histomorphometric changes including damage to seminiferous tubules, caput and caudal epididymal ducts were noted with decline in sperm concentration. Moreover, hepatorenal histological alterations were identified by leukocytic infiltration, cytoplasmic vacuolation in liver and shrinkage of glomerulus and tubular atrophy in the kidney. On contrary, fucoidan treatment reversed all MSG instigated alterations in dose dependent manner.These findings revealed that fucoidan mitigated MSG induced oxidative, genotoxic and histological alterations in rats, suggesting further mechanistic validation for translational relevance.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"603-619"},"PeriodicalIF":1.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259686","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

Blueberry anthocyanin extract inhibits platelet activation and FUNDC1-mediated mitophagy in type 2 diabetes mellitus via AMPK pathway. 蓝莓花青素提取物通过AMPK途径抑制2型糖尿病血小板活化和fundc1介导的线粒体自噬。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-07-01 Epub Date: 2026-06-14 DOI: 10.1080/00498254.2026.2686234

Qiang Wu, Yushi Bao, Kangkang Peng, Yaping Lou, Lulu Wang

{"title":"Blueberry anthocyanin extract inhibits platelet activation and FUNDC1-mediated mitophagy in type 2 diabetes mellitus via AMPK pathway.","authors":"Qiang Wu, Yushi Bao, Kangkang Peng, Yaping Lou, Lulu Wang","doi":"10.1080/00498254.2026.2686234","DOIUrl":"10.1080/00498254.2026.2686234","url":null,"abstract":"HPLC analysis was employed to identify the chemical compositions in BAE. Delphinidin, cyanidin, peonidin, and malvidin were detected in BAE.After establishment of the T2DM mice model, BAE and metformin were treated. Body weight, fasting blood glucose level and glucose tolerance were monitored, followed by detection of β-TG, PF4, CD62p, mitophagy markers. Both BAE and metformin implement reduced the body weight and fasting blood glucose level, and improved glucose tolerance of T2DM mice. BAE implement significantly reduced the β-TG, PF4 and CD62p levels in T2DM mice. FUNDC1, LC3II/LC3I, Pink1, and Parkin protein levels were both significantly elevated in T2DM mice, while Tomm20 expression was remarkedly reduced. BAE implement effectively reversed the FUNDC1, LC3II/LC3I, Pink1, and other relevant markers in T2DM mice.The effect of AMPK pathway involved in the BAE for T2DM treatment was explored. STZ treatment significantly decreased the phospho-AMPK level, while BAE administration reversed the effects of STZ on phospho-AMPK level in mice. Compound C implement effectively abolished the effects of BAE on the expression of platelet activation and mitophagy markers.This study suggests that BAE ameliorates T2DM through inhibiting platelet activation and FUNDC1-mediated platelet mitophagy via the AMPK pathway.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"594-602"},"PeriodicalIF":1.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200125","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