Toxicological Research最新文献_第5页

Effect of high caffeine exposure on longitudinal bone growth during puberty in immature female rats. 高咖啡因暴露对青春期未成熟雌性大鼠纵向骨生长的影响。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-22 eCollection Date: 2026-01-01 DOI: 10.1007/s43188-025-00314-y

Jihyun Keum, Yuri Choi, Ki-Young Ryu, Jeonghyeon Lee, Jaesook Roh

{"title":"Effect of high caffeine exposure on longitudinal bone growth during puberty in immature female rats.","authors":"Jihyun Keum, Yuri Choi, Ki-Young Ryu, Jeonghyeon Lee, Jaesook Roh","doi":"10.1007/s43188-025-00314-y","DOIUrl":"https://doi.org/10.1007/s43188-025-00314-y","url":null,"abstract":"Puberty is a critical period for skeletal growth. Although previous studies have demonstrated detrimental effects of caffeine on the skeletal system, most have used male rats to avoid the individual variability associated with rising estrogen in females. Hence, the effects of pubertal caffeine exposure on bone growth in females remain largely unknown. To investigate this, immature female Sprague-Dawley rats were assigned two experimental groups, which received caffeine doses of 120 and 180 mg/kg/day, respectively for 4 or 8 weeks, and a control group. At the end of the experiment, leg bone lengths and weights were measured, serum estradiol levels were determined, and histomorphometric analyses of the growth plates (GPs) were performed. Body weight was significantly lower in the two caffeine-fed groups than in the control group at both 4 and 8 weeks, and caffeine exposure significantly reduced leg bone length and weight, especially after 4 weeks of exposure. Bone mineral content was also reduced at both time points, whereas bone mineral density was affected only after 4 weeks. Notably, serum estradiol levels were significantly elevated in the caffeine-treated groups after 4 weeks of exposure. Histomorphometric analysis of the proximal tibial GP revealed that the caffeine-fed groups consistently had greater GP heights, lower bone formation parameters, and reduced spongiosa heights compared to controls. These findings suggest that caffeine directly or indirectly impairs the mineralization and osteoblastic activity required for proper bone maturation. Further research is needed to determine whether these adverse effects on long bone development in females persist following the cessation of caffeine exposure.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-025-00314-y.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 1","pages":"59-68"},"PeriodicalIF":2.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12770094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918665","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}

引用次数: 0

Is salsolinol a friend or foe? Revisiting its roles in neurotoxicity and cellular protection. salsolinol是朋友还是敌人？重新审视其在神经毒性和细胞保护中的作用。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-21 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00306-y

Chan-Mi Park, Hye-Kyung Na

{"title":"Is salsolinol a friend or foe? Revisiting its roles in neurotoxicity and cellular protection.","authors":"Chan-Mi Park, Hye-Kyung Na","doi":"10.1007/s43188-025-00306-y","DOIUrl":"https://doi.org/10.1007/s43188-025-00306-y","url":null,"abstract":"Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL) is a dopamine-derived tetrahydroisoquinoline, first identified in the urine of a Parkinson's disease patient treated with L-DOPA. SAL is generated endogenously via both enzymatic and non-enzymatic Pictet-Spengler condensation of dopamine with acetaldehyde. It is also found in dietary sources such as bananas, mushrooms, and cocoa, as well as in certain microbes. SAL has been detected in cerebrospinal fluid and various brain regions. SAL acts as a neuroactive compound implicated in ethanol's reinforcing effects and has been proposed as an endogenous prolactin-releasing factor. Its structural similarity to the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) has long provoked suspicions that SAL may induce dopaminergic neurodegeneration through generation of reactive oxygen species and subsequent activation of cell death pathways. However, recent in vitro and in vivo studies reveal a biphasic profile: at low concentrations, SAL exerts neuroprotective effects, whereas at higher concentrations, it becomes neurotoxic. This review therefore summarizes differential pathophysiological roles of SAL based on experimental and clinical findings, highlighting its context-specific, dose-dependent actions in the central nervous system.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"569-580"},"PeriodicalIF":2.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410194","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}

引用次数: 0

Integrated biomarker analysis and next-generation AI for precision diabetes prediction. 集成生物标志物分析和下一代人工智能精准预测糖尿病。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-16 eCollection Date: 2026-01-01 DOI: 10.1007/s43188-025-00312-0

Hyun Sim, Hyung-Ho Ha, Hangun Kim

{"title":"Integrated biomarker analysis and next-generation AI for precision diabetes prediction.","authors":"Hyun Sim, Hyung-Ho Ha, Hangun Kim","doi":"10.1007/s43188-025-00312-0","DOIUrl":"https://doi.org/10.1007/s43188-025-00312-0","url":null,"abstract":"This study explored the integration of advanced deep learning with key pharmaceutical biomarkers to enhance early diabetes prediction. We developed a multimodal ensemble approach that leverages transformer architectures to capture complex dependencies in heterogeneous healthcare data and Diffusion Models to address class imbalances by generating synthetic samples. Our research utilized diverse data sources, including electronic health records, medical imaging, and wearable device time-series data, supplemented with synthetic samples to better represent minority populations such as patients with type 1 and gestational diabetes. Critical biomarkers, including C-peptide, insulin, and hemoglobin A1c, were incorporated to improve model interpretability. The methodology involved extensive evaluation using accuracy, area under the receiver operating characteristic (ROC) curve (AUC), precision, recall, and F1-score, with cross-validation to mitigate overfitting. We also implemented interpretability features to provide clinicians with insight into the significance of biomarkers. Results showed a 6.2% improvement in minority class recall when pharmaceutical biomarkers were combined with diffusion-based augmentation. The model demonstrated enhanced classification stability and provided clear insights into clinical decision-making, highlighting the influence of biomarkers on disease progression and treatment outcomes. Future work will focus on multicenter validation, integration of additional omics data, and specialized validation across diverse populations. These findings underscore the potential of AI-driven biomarker analysis for advancing early diagnosis and personalized diabetes management, with broader implications for chronic disease prediction.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 1","pages":"35-46"},"PeriodicalIF":2.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12770190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918689","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}

引用次数: 0

Toxicity of Semaglutide upon sub chronic administration in Rabbits. 西马鲁肽对家兔亚慢性给药的毒性。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-08 eCollection Date: 2026-01-01 DOI: 10.1007/s43188-025-00308-w

Chandrashekara Vishwanath, Kumar Krishnachari, Gowrav Perdur Adiga, Manohar Madhavdeshmukh, Akanksh Das, Zabiullah Alandur Jamal, Prabhakar Bhoite, Kalaiselvan Ponnusamy, Mohan Krishnappa, Varun Ahuja, Manoj Kumar Pananchukunnath, Anil Kunhihitlu, Vikas Jain

{"title":"Toxicity of Semaglutide upon sub chronic administration in Rabbits.","authors":"Chandrashekara Vishwanath, Kumar Krishnachari, Gowrav Perdur Adiga, Manohar Madhavdeshmukh, Akanksh Das, Zabiullah Alandur Jamal, Prabhakar Bhoite, Kalaiselvan Ponnusamy, Mohan Krishnappa, Varun Ahuja, Manoj Kumar Pananchukunnath, Anil Kunhihitlu, Vikas Jain","doi":"10.1007/s43188-025-00308-w","DOIUrl":"https://doi.org/10.1007/s43188-025-00308-w","url":null,"abstract":"Semaglutide is an anti-obesity and anti-diabetic drug used in long-term weight management and for the treatment of type 2 diabetes. A toxicology study was conducted on a generic synthetic version of Semaglutide Injection (2 mg/3 mL) produced by Biocon Pharma, using New Zealand White Rabbits. In this study, Rabbits (4/sex/group) were administered subcutaneously, once weekly, with Semaglutide Injection at dose levels of 0.062, 0.124, and 0.248 mg/kg for a period of 90 days. Across all dose groups, treatment-related significant decreases in food consumption, weight loss, fewer fecal pellets, limited urine pools, and decreased activity were observed. These reported changes are known class effects of GLP-1 receptor agonists. Additionally, all changes noted in hematology, clinical, and anatomic pathology parameters were linked to reduced food intake and weight loss. Results showed one mortality each in treatment groups with Semaglutide administered at 0.124 mg/kg (mid dose) and 0.248 mg/kg (high dose). Mortality was related to the exaggerated pharmacological effect on body weight and feed consumption. Based on the findings from this study, the No-Observed-Adverse-Effect-Level (NOAEL) for Semaglutide Injection 2 mg/3 mL (0.67 mg/mL) was found to be 0.062 mg/kg in New Zealand White Rabbits.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 1","pages":"1-17"},"PeriodicalIF":2.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12770063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918715","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}

引用次数: 0

Chitooligosaccharides as a potential immune modulator for reducing particulate matter 10-induced inflammation in pulmonary damage models. 壳寡糖作为一种潜在的免疫调节剂，可减少肺损伤模型中颗粒物质引起的炎症。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-07 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00304-0

Chan-Ho Park, Yun-Ho Kim, Ju Myung Kim, Yeo Cho Yoon

{"title":"Chitooligosaccharides as a potential immune modulator for reducing particulate matter 10-induced inflammation in pulmonary damage models.","authors":"Chan-Ho Park, Yun-Ho Kim, Ju Myung Kim, Yeo Cho Yoon","doi":"10.1007/s43188-025-00304-0","DOIUrl":"https://doi.org/10.1007/s43188-025-00304-0","url":null,"abstract":"This study investigated the effects of chitooligosaccharides (COS) on proinflammatory cytokines and nuclear factor-κB (NF-κB) activation in particulate matter 10 (PM10)-induced mice. Results demonstrated that COS treatment significantly reduced proinflammatory cytokines, including interleukin (IL)-6 and IL-1β, particularly in the COS_20 group (20 mg/kg body weight of COS). Lower COS doses correlated with a dose-dependent decrease in proinflammatory cytokine levels and inflammatory cell infiltration in bronchoalveolar lavage fluid and lung tissue. COS treatment increased Th2 cell-related biomarkers (IL-4, IL-5, and IL-13), although these decreased at higher doses. Western blotting analysis revealed that COS suppressed NF-κB activation, particularly in the COS_20 group, suggesting that COS may inhibit IκB degradation, preventing NF-κB translocation to the nucleus and subsequent transcription of proinflammatory genes. These findings indicate that COS effectively mitigates the inflammatory response triggered by PM10 exposure, positioning it as a potential functional health supplement for managing pulmonary inflammation and related disorders.Graphical abstract: Supplementary information: The online version contains supplementary material available at 10.1007/s43188-025-00304-0.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"611-622"},"PeriodicalIF":2.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410148","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}

引用次数: 0

Amiodarone as a model compound for assessment of mitochondrial toxicity in hepatocytes. 胺碘酮作为肝细胞线粒体毒性评估的模型化合物。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-05 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00310-2

Jeongwoo Park, Munkyung Choi, Young-Joon Surh, Keon Wook Kang

{"title":"Amiodarone as a model compound for assessment of mitochondrial toxicity in hepatocytes.","authors":"Jeongwoo Park, Munkyung Choi, Young-Joon Surh, Keon Wook Kang","doi":"10.1007/s43188-025-00310-2","DOIUrl":"https://doi.org/10.1007/s43188-025-00310-2","url":null,"abstract":"Mitochondria are essential for cellular energy production and play a critical role in maintaining overall cellular homeostasis. Mitochondrial dysfunction primarily affects energy-demanding tissues such as heart and skeletal muscle, as well as tissues (e.g., the liver) that are exposed to xenobiotics. In fact, mitochondrial toxicity is recognized as a major contributor to drug-induced liver injury (DILI). However, reliable methods for assessment of mitochondrial toxicity in vitro or in vivo remain lacking. Here, through a series of in vitro and in vivo experiments, we identified amiodarone as a model compound for evaluation of mitochondrial toxicity in hepatocytes and liver tissues. Among five known hepatotoxic agents tested, amiodarone consistently induced characteristic features of mitochondrial toxicity, including reduced mitochondrial membrane potential, elevated mitochondrial reactive oxygen species (ROS), and disrupted mitochondrial dynamics in both primary hepatocytes and surrogate cell lines. Because mitochondrial damage frequently triggers activation of antioxidant defense pathways, we further confirmed increased antioxidant gene expression and serum transaminase level elevation in mice administered with amiodarone. Indeed, the hepatotoxicity induced by amiodarone was significantly enhanced in Nrf2-deficient mice. Our approach, importantly, can be applied to the evaluation of drug-induced mitochondrial damage in the liver.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-025-00310-2.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"635-647"},"PeriodicalIF":2.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410211","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}

引用次数: 0

Unveiling the intriguing potential of Bacopa monnieri extract in alleviating cypermethrin-induced hypothyroidism and oxidative stress in female mice. 揭示假马齿苋提取物缓解氯氰菊酯诱导的雌性小鼠甲状腺功能减退和氧化应激的有趣潜力。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-08-04 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00309-9

Surbhi Chourasiya, Anand Kar, Versha Sharma

{"title":"Unveiling the intriguing potential of Bacopa monnieri extract in alleviating cypermethrin-induced hypothyroidism and oxidative stress in female mice.","authors":"Surbhi Chourasiya, Anand Kar, Versha Sharma","doi":"10.1007/s43188-025-00309-9","DOIUrl":"https://doi.org/10.1007/s43188-025-00309-9","url":null,"abstract":"Cypermethrin (CYP) is a commonly used type II Pyrethroid pesticide, that normally accumulates in the various body tissues, causing organ dysfunction. In order to reduce its toxicity, we primarily investigated the potential of Bacopa monnieri (BM) extract in the amelioration of CYP-induced hypothyroidism in female Swiss mice. Animals were divided into 4 groups of 6 each. Group I, without receiving any treatment served as control, Group II was orally administered with CYP at 15 mg/kg, while Group III animals were administered only with BM extract at 200 mg/kg, and Group IV received equivalent dose of CYP along with BM extract (CYP + BM). The treatment was continued for 28 days. At the end, serum levels of triiodothyronine (T3), thyroxin (T4), and thyroid-stimulating hormone (TSH) were measured. Also, thyroidal histopathology and tissue peroxidation were evaluated. Results revealed that CYP administration induced hypothyroidism in the animals, as indicated by reduced serum thyroid hormones and enhanced TSH levels. Thyroid follicles were of reduced diameter and with flattened epithelium and vacuolated cytoplasm. Also, a significant increase in the body weight and thyroid weight was seen. Further, a decreased expression of TSHr and THR β-1 receptors was also found in this group. Interestingly, the co-administration of BM extract and CYP could ameliorate hypothyroidism in mice. A reversal in the pesticide-induced increase in oxidative stress was also seen in the CYP + BM group, suggesting a reduction in CYP-induced thyroid toxicity. BM was also found to be antiperoxidative. These results suggest the potential of BM extract in the mitigation of cypermethrin-induced Hypothyroidism and its adverse effects. This work further demonstrates the expression of TSHr and THR β-1 and suppression of the oxidative stress in the test extract administered to hypothyroid female mice.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"649-661"},"PeriodicalIF":2.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410219","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}

引用次数: 0

Mechanism of endoplasmic reticulum stress-induced endothelial cell ferroptosis in trichloroethylene-induced mouse kidney injury. 内质网应激诱导三氯乙烯致小鼠肾损伤内皮细胞铁下垂的机制。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-07-26 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00307-x

Meng Huang, Jiaxiang Zhang, Rui Li, Jian Chen, Qixing Zhu, Haibo Xie

{"title":"Mechanism of endoplasmic reticulum stress-induced endothelial cell ferroptosis in trichloroethylene-induced mouse kidney injury.","authors":"Meng Huang, Jiaxiang Zhang, Rui Li, Jian Chen, Qixing Zhu, Haibo Xie","doi":"10.1007/s43188-025-00307-x","DOIUrl":"https://doi.org/10.1007/s43188-025-00307-x","url":null,"abstract":"Trichloroethylene (TCE) is widely employed as a cleaning agent in industrial settings. Occupational exposure to TCE can lead to occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Our previous research has identified damage to renal vascular endothelial cells (ECs) in both OMDT patients and TCE-sensitized mice; however, the underlying mechanisms remain insufficiently understood. Methods: This study aims to elucidate the role of endoplasmic reticulum stress (ERS)-induced ECs ferroptosis in TCE-induced renal injury by developing a TCE-sensitization mouse model. Our findings indicate that ferroptosis in renal ECs is associated with TCE-induced kidney damage, and the ferroptosis inhibitor Fer-1 can mitigate this injury. Notably, ERS can modulate TCE-induced ECs ferroptosis. The PERK inhibitor GSK2606414 can suppress ferroptosis via the Nrf2/HO-1 signaling pathway and reduce trichloroethylene-induced renal injury. In conclusion, TCE sensitization activates ERS through the PERK/eIF2α/ATF4 pathway, with PERK subsequently mediating ferroptosis of renal vascular endothelial cells via the Nrf2/HO-1 signaling pathway, thereby contributing to TCE-related immune kidney injury.Graphical abstract: ","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"623-634"},"PeriodicalIF":2.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410153","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}

引用次数: 0

Oxidative stress and pancreatic cancer: a dual role in tumorigenesis and drug toxicity. 氧化应激与胰腺癌：在肿瘤发生和药物毒性中的双重作用。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-07-13 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00301-3

Khem Raj Limbu, Rashmi Bhandari Chhetri, Yoon Sin Oh, Min-Ho Oak, Dong Jae Beak, Eun-Young Park

{"title":"Oxidative stress and pancreatic cancer: a dual role in tumorigenesis and drug toxicity.","authors":"Khem Raj Limbu, Rashmi Bhandari Chhetri, Yoon Sin Oh, Min-Ho Oak, Dong Jae Beak, Eun-Young Park","doi":"10.1007/s43188-025-00301-3","DOIUrl":"https://doi.org/10.1007/s43188-025-00301-3","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and treatment-resistant malignancy with a poor prognosis. Among the multifactorial mechanisms implicated in the progression of PDAC, oxidative stress, defined as an imbalance between reactive oxygen species (ROS) and antioxidant defenses, has emerged as a crucial regulator of tumor behavior. While ROS can promote tumorigenesis via genomic instability, oncogenic signaling, and immune evasion, it also exhibits tumor-suppressive potential by inducing apoptosis and disrupting cancer cell metabolism. This dual role of ROS in PDAC is tightly influenced by the tumor mutational landscape, particularly KRAS gene mutations, metabolic reprogramming, and the tumor microenvironment. In PDAC, the generation of ROS promotes chemoresistance, activates hypoxia-inducible factor-1α, and facilitates desmoplastic stromal remodeling via pancreatic stellate cells and cancer-associated fibroblasts. Conversely, the therapeutic increase of ROS beyond tolerable levels induces cancer cell death through apoptosis and autophagy. This review comprehensively summarizes the dual role of ROS in PDAC, with particular emphasis on the molecular mechanisms underlying redox regulation. In addition, ROS-targeting therapeutic agents are categorized into clinically approved drugs, investigational agents, and natural compounds, and their relevance in redox biology is discussed. Finally, emerging therapeutic strategies that leverage redox vulnerabilities are outlined, and future research directions are proposed for the development of redox-modulating PDAC therapies.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"533-551"},"PeriodicalIF":2.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410212","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}

引用次数: 0

Bisphenol A and reproductive health: a comprehensive overview of toxicological effect. 双酚A与生殖健康：毒理学效应综合综述。

IF 2.3 4区医学

Toxicological Research Pub Date : 2025-07-10 eCollection Date: 2025-11-01 DOI: 10.1007/s43188-025-00305-z

Adfar Reyaz, Darakhshan Javaid, Syed Sanober Qadri, Shahid Yousuf Ganie, Mohd Salim Reshi

{"title":"Bisphenol A and reproductive health: a comprehensive overview of toxicological effect.","authors":"Adfar Reyaz, Darakhshan Javaid, Syed Sanober Qadri, Shahid Yousuf Ganie, Mohd Salim Reshi","doi":"10.1007/s43188-025-00305-z","DOIUrl":"https://doi.org/10.1007/s43188-025-00305-z","url":null,"abstract":"Bisphenol A (BPA), a synthetic compound extensively used in the production of polycarbonate plastics and epoxy resins, is a pervasive environmental contaminant and a potent endocrine disruptor. By mimicking oestrogen and binding to oestrogen receptors, BPA interferes with normal hormonal signalling, leading to significant disruptions in reproductive systems. In males, BPA exposure has been linked to reduced sperm count, impaired spermatogenesis, and histopathological alterations in testicular tissue, including disrupted Leydig cell function. In females, it affects ovarian follicle development, disrupts reproductive cyclicity, and causes morphological abnormalities in ovarian tissues. These reproductive effects are exacerbated by BPA-induced oxidative stress, which damages cellular structures and exacerbates hormonal imbalances. The mechanisms underlying BPA's reproductive toxicity involve disruptions in gene expression, signalling pathways, and hormonal homeostasis, highlighting its far-reaching effects on both male and female fertility. This study explores the hormonal havoc caused by BPA exposure, emphasizing its multifaceted impact on reproductive health and the urgent need for mitigative strategies to address its toxicity.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 6","pages":"553-567"},"PeriodicalIF":2.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410128","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}

引用次数: 0