Human & experimental toxicology最新文献

{"title":"Usnic Acid induces dual-pathway apoptosis in SKOV-3 ovarian cancer cells via PARP1 inhibition and MAPK pathway activation.","authors":"Mehmet Kürşat Derici, Mine Ensoy, Pelin Mutlu, Demet Cansaran-Duman","doi":"10.1177/09603271251409541","DOIUrl":"https://doi.org/10.1177/09603271251409541","url":null,"abstract":"<p><p>IntroductionDue to its silent clinical progression and diagnosis often occurring at advanced stages, ovarian cancer continues to be a major contributor to gynecological cancer-related mortality worldwide. Recent evidence underscores the critical therapeutic value of targeting the interplay between DNA damage response pathways, particularly poly (ADP-ribose) polymerase 1 (PARP1), and mitogen-activated protein kinase (MAPK) signaling cascades.MethodsIn this study, we investigated the anti-cancer potential of the naturally derived small molecule usnic acid in a chemotherapy-resistant epithelial ovarian cancer model (SKOV-3 cells) at the cellular and molecular levels.ResultsOur findings demonstrate for the first time that usnic acid exerts a dual-pathway apoptotic mechanism by simultaneously inhibiting PARP1 and activating the MAPK signaling pathway. Remarkably, usnic acid mimics the gene-silencing action of siRNA on PARP1, suggesting a highly specific and potent inhibitory effect at the molecular level. Although ROS involvement and pathway causality were not directly tested, this dual-action profile enhances DNA damage-induced apoptosis and highlights usnic acid as a promising therapeutic candidate.ConclusionThe study presents a novel molecular framework in which a single small molecule can coordinate apoptosis through parallel regulatory pathways, demonstrating the potential for innovative therapeutic approaches in the treatment of aggressive and treatment-resistant ovarian cancers.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251409541"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Ginsenoside Re suppresses high glucose-induced apoptosis of placental trophoblasts through endoplasmic reticulum stress-related CHOP/GADD153.","authors":"Guihong Zeng, Weiyang Zou, Changdi Liu, Yulan Chen, Tingmei Wen","doi":"10.1177/09603271241307835","DOIUrl":"10.1177/09603271241307835","url":null,"abstract":"<p><p><b>Background:</b> Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. <b>Purpose:</b> This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153. <b>Research Design:</b> Human trophoblast cells HTR-8/SVneo were treated with HG to simulate the HG environment <i>in vitro</i>, while normal glucose (NG) was used as the control. <b>Study Sample:</b> NG (5 mM) or HG (25 mM)-cultured HTR-8/SVneo cells were treated with 10, 20 or 40 μM Re. HG-cultured cells were treated with 5 mM ERS inducer 2-Deoxy-D-glucose (2-DG) and transfected with oe- CHO. <b>Data Collection and/or Analysis:</b> Cell viability and apoptosis were detected by CCK-8 and flow cytometry; LDH release, superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels were detected using kits; the apoptosisrelated proteins and ERS-related proteins were assessed by western blot. <b>Results:</b> Re (10, 20 or 40 μM) had no significant effect on NG-treated HTR-8/SVneo cell viability. Re (20 or 40 μM) could enhance the viability of HG-treated trophoblasts. Re (40 μM) inhibited apoptosis of HGtreated trophoblasts, ERS and alleviated oxidative stress evidenced by suppressed phosphorylation of PERK, IRE1α, reduced protein expression of ATF6, CHOP/GADD153, and inhibited MDA accumulation, GSH and SOD loss. ERS activation or CHOP/GADD153 overexpression reversed Re's inhibition on HG-induced apoptosis of trophoblasts. <b>Conclusions:</b> Re repressed HG-induced placental trophoblast apoptosis by mediating ERS-related protein CHOP/GADD153.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271241307835"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Octreotide ameliorates Bisphenol A-induced testicular toxicity via autophagy-inflammation pathway modulation.","authors":"Basma B Morad, Ola M Salem, Rasha Osama El-Esawy, Fleur F Abd Elmonem","doi":"10.1177/09603271251388830","DOIUrl":"https://doi.org/10.1177/09603271251388830","url":null,"abstract":"<p><p>IntroductionTesticular toxicity commonly manifests as impaired spermatogenesis and testicular atrophy. Bisphenol A (BPA), a commonly used organic plasticizer, negatively affects sperm parameters, hormonal levels, and fertility. Octreotide (OCT), a somatostatin analog, was originally used to treat acromegaly, carcinoid tumors, vasoactive intestinal peptide-secreting, and growth hormone-secreting tumors. OCT has demonstrated potential therapeutic properties beyond its traditional use in endocrine disorders. We hypothesized that OCT would attenuate BPA-induced testicular damage through its anti-inflammatory, anti-oxidant, and anti-autophagic properties. This study aimed to assess the mechanisms of BPA-induced testicular toxicity and evaluate the ameliorative effects of OCT.MethodsForty adult male Sprague Dawley (SD) rats were randomly assigned to four equal groups: group1: saline control, group2: dimethyl sulfoxide (DMSO) vehicle, group3: BPA-treated, and group4: BPA + OCT-treated. Treatments were administered for 4 weeks. Sperm count, testicular weight, serum testosterone, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total antioxidant capacity (TAC), testicular levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα), Beclin-1 (BECN-1), Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A/LC3), mammalian target of rapamycin (M-TOR), histopathological examination, apoptotic index, and Johnson's score were assessed.ResultsBPA administration significantly impaired spermatogenesis, reduced serum testosterone and TAC, and increased MDA, TNFα, and autophagy-related markers, along with histopathological damage of testis. Co-treatment with OCT mitigated these effects by improving sperm parameters, hormone levels, oxidative stress markers, inflammatory cytokines, and testicular histology.DiscussionThe findings suggest that OCT exerts a protective effect against BPA-induced testicular toxicity, through its anti-inflammatory, antioxidant, and autophagy-modulating properties. OCT may offer therapeutic potential in mitigating BPA-induced testicular toxicity.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251388830"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The safety assessment of N-<i>trans</i>-feruloyltyramine using <i>In vitro</i> genotoxicity studies and 90-day toxicity study in rats.","authors":"Sungwon Lee, Srinivas Seekallu, Suresh Babu Venkataramaiah, Chandrashekar Mataguru Doreswamy, Mohan Cheluru Umesh, Sandeep Malleshappa, Sajeev Justin Dev, Ganadhal Puttaramaiah Chethankumara, Nagaraju Lohith, Gajanan Rajpal Deshmukh, Brian Premkumar, Brinda Mahadevan","doi":"10.1177/09603271251334452","DOIUrl":"https://doi.org/10.1177/09603271251334452","url":null,"abstract":"<p><p>IntroductionN-<i>trans</i>-feruloyltyramine (NFT) is a bioactive compound present in many plant sources. The purpose of the studies was to investigate adverse effects, if any, of NFT produced through precision fermentation.MethodsAn <i>in vitro</i> Ames test was performed with NFT using bacterial strains at concentrations up to 1580 µg/plate with and without S9. The <i>in vitro</i> micronucleus assay was performed in human peripheral blood cells in culture, with and without, metabolic activation at three different doses. In the subchronic toxicity study, adult Sprague Dawley rats (10/sex/group) were fed diets prepared with target doses of 0, 5000, 10,000 or 20,000 ppm of NFT for 90 days.ResultsIn the Ames assay, there were no NFT-related or concentration dependent increases in revertant colony numbers in any of the tester strains. In the <i>in vitro</i> micronucleus assay, there was no statistically significant increase in the number of binucleated cells with micronuclei compared to the vehicle control. NFT was found to be non-genotoxic when evaluated in the <i>in vitro</i> Ames and micronucleus assays. In the 90-day rodent study, NFT was well tolerated, with no related adverse findings observed at any of the dose levels tested. There were no NFT related adverse histopathological changes observed in the high dose group of both the sexes.ConclusionThe No observed adverse effect level of NFT was determined as 1474 mg/kg body weight/day in males and 1958 mg/kg body weight/day in females based on the actual intake at the dose levels tested and under the experimental conditions employed.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251334452"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Effect of grape seed extract ondoxorubicin-induced testicular andepididymal damage in rats\".","authors":"","doi":"10.1177/09603271251341390","DOIUrl":"https://doi.org/10.1177/09603271251341390","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251341390"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human health risk assessment of heavy metals in different compartments of vegetables from Erbil City-Iraq.","authors":"Bashdar Abuzed Sadee","doi":"10.1177/09603271251351421","DOIUrl":"https://doi.org/10.1177/09603271251351421","url":null,"abstract":"<p><p>IntroductionThe consumption of vegetables is a key route for increasing the content of potentially toxic heavy metals in the food chain. This article aimed to quantify the concentrations of As, Se, Cd, Cr, Co, Cu, Ni, and Pb in different parts of vegetables harvested from Erbil city.MethodologyThe total concentrations of As, Cd, Cr, Co, Cu, Ni, and Pb in various vegetable parts were pursued by ICP-MS analysis.ResultsThe values of heavy metals in different parts of the analyzed vegetables ranged from 0.052 to 2.106 mg/kg for As, 0.024 to 5.899 mg/kg for Se, 0.014 to 0.753 mg/kg for Cd, 0.441 to 89.400 mg/kg for Cr, 0.052 to 2.693 mg/kg for Co, 0.737 to 39.120 mg/kg for Cu, 0.301 to 63.880 mg/kg for Ni, and 0.032 to 1.782 mg/kg for Pb. The Hazard Quotient (HQ) values for As, Cr, Cu, and Ni in the edible parts of most vegetables exceeded one, while those for Se, Co, Cd, and Pb were below one.DiscussionIn contrast to Se, Co, Cd, and Pb, the HQ values for As, Cr, and Pb indicate a potential health risk when consuming these edible parts of the vegetables. The Hazard Index (HI) for all edible parts of the analyzed vegetable samples exceeded one. The cancer risk (CR) of As, Cd, Cr and Ni were higher than 1.0 × 10^-4 which indicating carcinogenic risk. As a result, regular consumption of these vegetables is regarded as unsafe and not advisable.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251351421"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and validation of an <i>in vitro</i> liver model based extracellular matrix for hepatotoxicity prediction.","authors":"Yue Yu, Haodong Zhong, Qianyi Niu, Manman Zhao, Bo Li, Xiaobing Zhou","doi":"10.1177/09603271251350797","DOIUrl":"https://doi.org/10.1177/09603271251350797","url":null,"abstract":"<p><p>IntroductionThree-dimension (3D) cell culture presents a promising alternative of drug-induced liver injury (DILI). To advance preclinical toxicology research, we developed an <i>in vitro</i> liver model using HepG2 for toxic evaluation.MethodsThe model was constructed based on the extracellular matrix. We assessed its long-term stability by monitoring the morphological change and anabolic capacity for 2 weeks, with functional analyses including albumin/urea production, lipid accumulation with Nile red staining, bile secretion with CLF signal, and transporter/enzyme expression including PGP, MRP2, BSEP, and CYP3A4.ResultsThe model could be maintained for at least 10 days with enhanced hepatic synthetic functions indicated by albumin and urea nitrogen. Compared with the two-dimensional (2D) cultures, 3D culture exhibited enhanced lipid accumulation and biliary excretion. Key hepatic transporters PGP, MRP2, and BSEP and the metabolic enzyme cytochrome P450 3A4 were expressed between day 5 and 7. Single-exposure induced measurable apoptosis, mitochondrial disfunction and viability assays, while repeated treatment replicated impaired bile acid transport by reduced CLF intensity, and cytotoxicity with elevated AST, ALT, and decreased survival.DiscussionOur 3D model surpasses conventional 2D systems in culture duration and functional complexity. It is suitable for DILI prediction after single- and repeated- treatment, which makes it particularly valuable for preclinical drug screening.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251350797"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and the risk factors analysis in patients with delayed encephalopathy after acute carbon monoxide poisoning.","authors":"Ziang Han, Sumeng Shi, Yan Zhang, Ding Yuan, Zhigao Xu, Yanxia Gao","doi":"10.1177/09603271251332234","DOIUrl":"10.1177/09603271251332234","url":null,"abstract":"<p><p>IntroductionAcute carbon monoxide poisoning (ACMP) remains a leading cause of morbidity and mortality from fatal inhaled poisoning. Delayed encephalopathy after ACMP (DEACMP) has become one of the most complex and serious complications.MethodsIn this research, an observational study was performed from January 2016 to December 2019 to investigate the potential relevant risk factors of DEACMP with data collected from Level 3 medical facilities located in Northern China. Within the 4-year data collection period, the final study cohort consisted of 240 (117 males, 123 females).ResultsUni-variable analysis identified older age, medical history of cerebrovascular accident, basic disease of diabetes, and longer duration of loss of consciousness as relevant factors for DEACMP; while multivariable logistic regression revealed that the older age (OR, 1.45; 95% CI, 1.25-1.69; <i>P</i> < 0.01), longer duration of loss of consciousness (OR, 1.39; 95% CI, 1.36-1.45; <i>P</i> < 0.01), and cerebrovascular accidents occurring (OR, 1.23; 95% CI, 1.03-1.47; <i>P</i> = 0.04) were independent predictors for DEACMP.DiscussionFurthermore, additional research is needed to testify to the relevance and to elucidate the potential pathogenesis, consequently determining the clinical guideline and approving the best prevention and treatment strategy for DEACMP.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nickel; a metal with threats to human health, focusing on its intoxication mechanisms.","authors":"Mehrdad Rafati Rahimzadeh, Mehravar Rafati Rahimzadeh, Sohrab Kazemi, Ali Akbar Moghadamnia","doi":"10.1177/09603271251361197","DOIUrl":"https://doi.org/10.1177/09603271251361197","url":null,"abstract":"<p><p>Background and ObjectiveNi is an important metal found in the human environment, including air, water, soil, food, kitchenware, and jewelry. It is widely used in electrical engineering, medicine, and industry. Ni compounds, whether insoluble (such as oxides and sulfides) or soluble (such as sulfates, chlorides, and acetates), pose serious risks to the environment, ecosystems, and human health. Such contamination can lead to harmful effects, especially on the respiratory, digestive, and skin systems. This study aims to emphasize the importance of early detection and diagnosis of Ni poisoning, as well as urgent measures and treatments, especially the use of chelators, in addition to the use of nanoparticles to remove nickel compounds from the environment.Methods and ResultThis review article draws on sources from PubMed, Scopus, various citations, and the Toxicologic Emergencies reference book spanning 1996-2025. The findings indicate that high-level exposure to nickel compounds leads to the formation of reactive oxygen species, suppression of DNA repair mechanisms, and disruption of signal transduction pathways. These effects result in genotoxicity, carcinogenicity, immunotoxicity, and poisoning across different species.ConclusionA thorough history and examination are essential for evaluating blood and urine nickel levels, as they directly relate to the severity of poisoning. Preventive measures involve avoiding nickel compounds and facilitating removal from the body. Allergic contact dermatitis is treated with antihistamines, corticosteroids, and calcineurin inhibitors like tacrolimus. For nickel poisoning treatment, chelators such as diethyl-dithiocarbamate (DDC) and disulfiram are prescribed based on urine concentration. Recently, nanoparticles have been used to remove nickel compounds from the environment.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251361197"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Protective effects of casein-derived peptide VLPVPQK against hydrogen peroxide-induced dysfunction and cellular oxidative damage in rat osteoblastic cells.","authors":"","doi":"10.1177/09603271251389836","DOIUrl":"https://doi.org/10.1177/09603271251389836","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251389836"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}