IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-22 DOI: 10.1080/00498254.2025.2517113

Sadaf Jamal Gilani, Najla Altwaijry, Ahlam Mansour Sultan, Reem Basoudan, Reem Albesher, Kaneez Fatima

{"title":"Formulation of apigenin-loaded solid lipid nanoparticles: characterisation, molecular docking, and anticancer assay.","authors":"Sadaf Jamal Gilani, Najla Altwaijry, Ahlam Mansour Sultan, Reem Basoudan, Reem Albesher, Kaneez Fatima","doi":"10.1080/00498254.2025.2517113","DOIUrl":"10.1080/00498254.2025.2517113","url":null,"abstract":"1. Apigenin (APN), a natural flavonoid, showed strong therapeutic potential against skin cancer, but its clinical use is restricted due to its complex physicochemical characteristics.2. Hence, this study aimed to fabricate APN-loaded solid lipid nanoparticles (APN-SLNs) for improved topical treatment of skin cancer. The developed APN-SLNs were evaluated for particle characterization, compatibility and crystallinity by employing FT-IR, DSC, and XRD. The selected APN-SLNs-loaded hydrogels further evaluated for gel evaluation, permeation and cytotoxicity assessment. The findings also supported with molecular docking study.3. The developed APN-SLNs demonstrated nanometric size, low polydispersity index, negative surface charge, high encapsulation efficiency and a biphasic release profile. The developed APN-SLNs-loaded hydrogels represented comparatively higher viscosity, firmness, consistency, and cohesiveness compared with the pure APN-loaded hydrogels. The APN-SLNs-loaded hydrogels represented >2 times higher in vitro permeation than pure APN-loaded hydrogels. Further, MTT assay using B16-F10 melanoma cells revealed the superior cytotoxic potential of the developed nanocarrier than the native counterpart. The docking study also supports the findings of the cell viability assay with a high docking score.4. Therefore, this study suggests that topical delivery of APN encapsulated in SLNs is a promising approach for skin cancer management.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267401","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

Exposure to crack cocaine induces genotoxicity and degenerative changes in multiple organs of Wistar rats. 暴露于快克可卡因可引起Wistar大鼠多器官的遗传毒性和退行性改变。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-21 DOI: 10.1080/00498254.2025.2522737

Daniel Vitor de Souza, Barbara Dos Anjos Rosario, Lorrany Da Silva Avanci, Gabriel Carvalhal de Aguiar, Viviane Carlin, Milena De Barros Viana, Daniel Araki Ribeiro

{"title":"Exposure to crack cocaine induces genotoxicity and degenerative changes in multiple organs of Wistar rats.","authors":"Daniel Vitor de Souza, Barbara Dos Anjos Rosario, Lorrany Da Silva Avanci, Gabriel Carvalhal de Aguiar, Viviane Carlin, Milena De Barros Viana, Daniel Araki Ribeiro","doi":"10.1080/00498254.2025.2522737","DOIUrl":"https://doi.org/10.1080/00498254.2025.2522737","url":null,"abstract":"Crack cocaine is a widely consumed illicit substance worldwide. Recent studies identify Brazil as the largest consumer of crack cocaine. This study evaluated its harmful effects on various organs in rats. Twenty-four male Wistar rats were distributed into four groups: G1 - exposed to 25 mg of crack cocaine; G2 - 50 mg; G3 - 100 mg; and a control group with no intervention. The experimental groups inhaled crack cocaine smoke once daily for five days. Histopathological changes were observed in the liver of G3 and in the kidneys of all exposed groups. Increased 8-OHdG immunoexpression occurred in the kidneys of G1 and G2. Ki-67 immunoexpression in the liver and kidneys was elevated in G1 and G2. GST-P-positive foci increased in G1 and G2. Micronucleated cells in bone marrow were significantly higher in all exposed groups. In the liver, hepatocytes with micronuclei increased in G1 and G2, while binucleated cells were more frequent in G3. Karyolysis increased in G2 and G3, and karyorrhectic hepatocytes were more frequent in G1 and G2. These findings demonstrate that inhalation exposure to crack cocaine induces degenerative and genotoxic effects in the liver, kidneys, and bone marrow of Wistar rats. These results offer new insights into the carcinogenic potential of crack cocaine in multiple organs, underscoring the need for public health interventions among its users.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-20"},"PeriodicalIF":1.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340469","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

Quantitative prediction of drug-drug interactions arising from CYP3A4 induction using chimeric mice with humanized liver. 人源化肝脏嵌合小鼠诱导CYP3A4引起的药物相互作用的定量预测。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-18 DOI: 10.1080/00498254.2025.2518239

Keigo Nakayama, Tamotsu Negoro, Hiroaki Takubo, Asami Hayashi, Toshio Taniguchi, Yukihiro Nomura, Kazunori Iwanaga

{"title":"Quantitative prediction of drug-drug interactions arising from CYP3A4 induction using chimeric mice with humanized liver.","authors":"Keigo Nakayama, Tamotsu Negoro, Hiroaki Takubo, Asami Hayashi, Toshio Taniguchi, Yukihiro Nomura, Kazunori Iwanaga","doi":"10.1080/00498254.2025.2518239","DOIUrl":"10.1080/00498254.2025.2518239","url":null,"abstract":"We aimed to establish an approach to quantitatively predict drug-drug interactions arising from cytochrome P450 (CYP) 3A4 induction using chimeric mice with humanised liver.After repeated administration of rifampicin or efavirenz as CYP inducers to chimeric mice, the relative expression of human CYP3A4 in their livers was measured and plotted against the area under the concentration-time curve (AUC) of rifampicin and efavirenz, respectively, in plasma on the final day of administration. Induction curves were obtained by fitting the plots.Assuming a similar relationship of relative CYP3A4 expression to AUC in chimeric mice as in humans, the relative CYP3A4 expression by clinical doses of rifampicin and efavirenz were calculated from the estimated clinical exposure.The calculated relative CYP3A4 expression was reflected in the intrinsic clearance of midazolam or alfentanil coadministered with a CYP inducer. The intrinsic clearance was incorporated into a constructed physiologically based pharmacokinetic model, which successfully predicted the pk change of midazolam or alfentanil coadministered with a CYP inducer or not. The results confirmed that our approach is useful to improve the prediction accuracy of CYP3A4 induction in the preclinical phase.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-12"},"PeriodicalIF":1.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276144","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

In Silico Analysis of Nicotine's Molecular Targets in Parkinson's Disease. 帕金森病中尼古丁分子靶点的计算机分析。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-18 DOI: 10.1080/00498254.2025.2519826

Hai Duc Nguyen

{"title":"In Silico Analysis of Nicotine's Molecular Targets in Parkinson's Disease.","authors":"Hai Duc Nguyen","doi":"10.1080/00498254.2025.2519826","DOIUrl":"https://doi.org/10.1080/00498254.2025.2519826","url":null,"abstract":"Purpose: we aimed to elucidate the molecular processes involved in how nicotine affects PD.Methods: toxicogenomic, molecular mechanisms, physicochemical properties, pharmacokinetic profile, and biological activity were analyzed.Results: We found that the therapeutic potential of nicotine in PD may be attributed to its ability to modulate the expression of 38 genes, especially GAPDH, TNF, IL6, and BDNF. The molecular mechanisms underlying the protective effects of nicotine against PD involve several pathways, including the \"Parkinson's disease pathway\", \"the selenium micronutrient network\", \"the oxidative stress response\", \"dopamine binding\", \"Parkinsonian disorders\", and \"Lewy body disease\". miRNAs like hsa-miRNA-203a-3p and miRNA-26b-5p and transcription factors like HNF4, MAPK3, and EVI1 explained how nicotine protects neurons from PD. An assessment was also carried out on drug candidates (polaprezinc) and miRNA sponges (hsa-miR-181a-5p, hsa-miR-124-3p, hsa-miR-1-3p) that may possess the capability to synergize the effects of nicotine. Nicotine's physicochemical properties, pharmacokinetic profile, and biological activity are conducive to its favorable attributes in the context of PD, including high gastrointestinal absorption, ability to penetrate the blood-brain barrier, non-P-glycoprotein nature, and antiparkinsonian effects.Conclusion: Nicotine plays crucial roles in the pathophysiology of PD. Further work is needed to evaluate the impact of nicotine on non-motor symptoms.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-35"},"PeriodicalIF":1.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326999","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 Antihypertensive Effects of Ophioglossum vulgatum: In Silico and In Vivo Evidence in Spontaneously Hypertensive. 蛇舌草抗高血压作用的评价：自发性高血压的体内和计算机证据。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-17 DOI: 10.1080/00498254.2025.2519820

Zi-Han Shen, Baozhen Chen, Congchao Wan, Jia-Xin Ye, Zixing Li, Shuang Lin, Xin Zhang, Yuehua Huang, Max K Leong, Tongjie Ye, Rong Wang, Yaw-Syan Fu

{"title":"Evaluation of Antihypertensive Effects of Ophioglossum vulgatum: In Silico and In Vivo Evidence in Spontaneously Hypertensive.","authors":"Zi-Han Shen, Baozhen Chen, Congchao Wan, Jia-Xin Ye, Zixing Li, Shuang Lin, Xin Zhang, Yuehua Huang, Max K Leong, Tongjie Ye, Rong Wang, Yaw-Syan Fu","doi":"10.1080/00498254.2025.2519820","DOIUrl":"https://doi.org/10.1080/00498254.2025.2519820","url":null,"abstract":"Hypertension is a widespread condition in the present day. This study investigated and evaluated the antihypertensive effects and mechanisms of Ophioglossum vulgatum（OV） through a combination of computational simulations and in vivo experiments. First, an in silico analysis using network pharmacology was employed to identify target proteins, followed by molecular docking and molecular dynamics simulations. Network pharmacology data indicated that OV may influence several pathways involved in blood pressure regulation. Molecular docking revealed the effective targets of OV, showing that some of its major active compounds could potentially bind directly to the active sites of angiotensin receptors and calcium channel proteins. In vivo experiments demonstrated that administration of 20 mg/kg crude OV extract to spontaneously hypertensive rats (SHRs) significantly reduced mean blood pressure by 31.53% within 60 minutes, alleviating hypertensive symptoms. Based on our in silico and in vivo evidence, the rapid antihypertensive effects of OV may be related to its action on the RAS and calcium channels, leading to vasodilation. These acute antihypertensive effects suggest that OV has the potential to be a candidate for blood pressure medication, particularly for urgent blood pressure reduction, and an effective antihypertensive agent in plant-based medicine.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-15"},"PeriodicalIF":1.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318122","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

Association of valproic acid-related pharmacodynamics, pharmacokinetic pathways and transporter gene polymorphisms and antiepileptic efficacy in Chinese Patients. 中国患者丙戊酸相关药效学、药动学途径和转运体基因多态性与抗癫痫疗效的关系。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-17 DOI: 10.1080/00498254.2025.2519825

Linlin Wang, Guangting Zeng, Jianqiang Li, Huilan Li, Jia Luo, Zanling Zhang

{"title":"Association of valproic acid-related pharmacodynamics, pharmacokinetic pathways and transporter gene polymorphisms and antiepileptic efficacy in Chinese Patients.","authors":"Linlin Wang, Guangting Zeng, Jianqiang Li, Huilan Li, Jia Luo, Zanling Zhang","doi":"10.1080/00498254.2025.2519825","DOIUrl":"https://doi.org/10.1080/00498254.2025.2519825","url":null,"abstract":"Valproic acid(VPA) has great individual differences in clinical efficacy, the study aimed to investigate the effects of VPA-related pharmacogenomics on the antiepileptic efficacy of VPA, so as to provide evidence for clinical rational drug use.The patients were followed up for one year, and the number of seizures within one year was used as the evaluation index of efficacy. The target SNPS were genotyped by SNPscan method.A total of 253 patients with epilepsy treated with valproate monotherapy were enrolled in this study, including 125 patients in the valproate-sensitive group and 128 patients in the valproate-resistant group. χ2 test showed that the frequency of C allele of CACNA1H rs3751664 in valproate-sensitive group was significantly higher than that in valproate-resistant group (93.6% vs. 87.5%, P = 0.023), and the difference was still statistically significant after adjusting for confounding factors by logistic regression analysis(P = 0.037). Haplotype analysis showed no association between gene polymorphisms and efficacy of valproic acid.CACNA1C rs1051375 GG and GA genotype patients have a lower risk of drug resistance than AA genotype patients, CACNA1H rs3751664 T allele is a risk factor for VPA monoresistance, while APEH rs3816877 CT genotype patients have a trend of drug resistance during VPA treatment.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-20"},"PeriodicalIF":1.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318120","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

Beta-aminoisobutyric acid attenuates doxorubicin-induced cardiotoxicity through the adenosine 5'-monophosphate-activated protein kinase-mediated pathway. β -氨基异丁酸通过腺苷5'-单磷酸活化蛋白激酶介导的途径减弱阿霉素诱导的心脏毒性。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-06-17 DOI: 10.1080/00498254.2025.2520423

Jietao Huang, Mao Sun, Jing Yu, Yihong Guo, Li Baoshan, Linyan Dai, Yangyang Tang, Xingsheng Wang, Shubo Han, Xia Lai

{"title":"Beta-aminoisobutyric acid attenuates doxorubicin-induced cardiotoxicity through the adenosine 5'-monophosphate-activated protein kinase-mediated pathway.","authors":"Jietao Huang, Mao Sun, Jing Yu, Yihong Guo, Li Baoshan, Linyan Dai, Yangyang Tang, Xingsheng Wang, Shubo Han, Xia Lai","doi":"10.1080/00498254.2025.2520423","DOIUrl":"https://doi.org/10.1080/00498254.2025.2520423","url":null,"abstract":"In this study, the adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mechanisms underlying the effect of β-aminoisobutyric acid (BAIBA), an exercise-induced myokine, in mitigating doxorubicin (DOX)-induced cardiotoxicity were investigated. In vitro/vivo DOX-induced injury models were constructed, and their cardiac functions were detected by echocardiography/histology. Moreover, serum biomarkers including lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), and brain natriuretic peptide (BNP) were measured. The mitochondrial ultrastructure was examined by transmission electron microscopy (TEM), and the generation of reactive oxygen species (ROS) was checked by MitoSOX™ Red staining. The analysis results showed that BAIBA significantly preserved the cardiac systolic function, reduced myocardial damage, and attenuated mitochondrial dysfunction, as evidenced by maintained cristae integrity and suppressed ROS overproduction. The mechanism was that BAIBA enhanced cardiac AMPK phosphorylation, while dorsomorphin abrogated the antioxidant effects of AMPK through inhibiting its activation. The findings demonstrate that BAIBA counteracts DOX cardiotoxicity via AMPK-mediated mitochondrial bioenergetic preservation. It provides a novel cardioprotective therapy as an exercise-mimetic adjuvant.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318121","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

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 : 2025-06-08 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":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2025-06-08","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 : 2025-06-04 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":"1-11"},"PeriodicalIF":1.3,"publicationDate":"2025-06-04","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

Genetic polymorphisms of ABCC2 and CBR3 can influence the efficacy and toxicity of doxorubicin therapy in Egyptian patients with non-Hodgkin lymphoma. ABCC2和CBR3基因多态性可影响阿霉素治疗埃及非霍奇金淋巴瘤患者的疗效和毒性。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-29 DOI: 10.1080/00498254.2025.2508814

Hagar A Elmekawy, Khaled Abdelkawy, Galal Magdy, Emad Sadaka, Gamal El-Azab, Ahmed Ali, Noha El-Khodary, Fawzy Elbarbry

{"title":"Genetic polymorphisms of ABCC2 and CBR3 can influence the efficacy and toxicity of doxorubicin therapy in Egyptian patients with non-Hodgkin lymphoma.","authors":"Hagar A Elmekawy, Khaled Abdelkawy, Galal Magdy, Emad Sadaka, Gamal El-Azab, Ahmed Ali, Noha El-Khodary, Fawzy Elbarbry","doi":"10.1080/00498254.2025.2508814","DOIUrl":"10.1080/00498254.2025.2508814","url":null,"abstract":"This study investigated the impact of single nucleotide polymorphisms (SNPs) in genes involved in doxorubicin (DOX) transport and metabolism on clinical outcomes and toxicity in Egyptian patients with non-Hodgkin lymphoma.Ninety-two patients received at least six DOX treatment cycles. SNP genotyping was performed using real-time PCR with high-resolution melting analysis. Laboratory tests were conducted at baseline, during, and after treatment.The AA genotype of ABCC2 (rs8187710) showed the strongest association with elevated DOX plasma levels and a significantly increased risk of acute cardiotoxicity (OR 26.9; 95% CI: 1.47-492; p = 0.026). The GA genotype was linked to a lower complete response rate and increased risks of leukopoenia (OR 2.66; 95% CI: 1.07-6.61; p = 0.034) and lymphocytopenia (OR 10; 95% CI: 3.57-27.9; p < 0.0001), with intermediate peak DOX levels. For CBR3 (rs8133052), the GA genotype was significantly associated with a higher risk of anaemia (OR 3.5; 95% CI: 1.05-11.7; p = 0.042), acute cardiotoxicity (OR 4.4; 95% CI: 1.86-11.5; p = 0.002), cardiac-related symptoms, and higher peak plasma DOX levels, along with reduced complete response.Polymorphisms in ABCC2 and CBR3 genes may contribute to individual variability in DOX-related toxicity and treatment response.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-11"},"PeriodicalIF":1.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120981","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

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