Current Research in Toxicology最新文献

{"title":"Estrogen replacement therapy reverses spatial memory loss and pyramidal cell neurodegeneration in the prefrontal cortex of lead-exposed ovariectomized Wistar rats","authors":"Abiodun Shukrat Lasisi-Sholola ,&nbsp;Sodiq Opeyemi Hammed ,&nbsp;Richard Adedamola Ajike ,&nbsp;Roland Eghoghosoa Akhigbe ,&nbsp;Oladele Ayobami Afolabi","doi":"10.1016/j.crtox.2024.100200","DOIUrl":"10.1016/j.crtox.2024.100200","url":null,"abstract":"<div><h3>Background</h3><div>Although menopause is a component of chronological aging, it may be induced by exposure to heavy metals like lead. Interestingly, lead exposure, just like the postmenopausal state, has been associated with spatial memory loss and neurodegeneration; however, the impact of hormone replacement therapy (HRT) on menopause and lead-induced spatial memory loss and neurodegeneration is yet to be reported.</div></div><div><h3>Aim</h3><div>The present study investigated the effect and associated mechanism of HRT on ovariectomized-driven menopausal state and lead exposure-induced spatial memory loss and neurodegeneration.</div></div><div><h3>Materials and methods</h3><div>Thirty adult female Wistar rats were randomized into 6 groups (n = 5 rats/group); the sham-operated vehicle-treated, ovariectomized (OVX), OVX + HRT, lead-exposed, OVX + lead, and OVX + Lead + HRT groups. Treatment was daily via gavage and lasted for 28 days.</div></div><div><h3>Results</h3><div>Ovariectomy and lead exposure impaired spatial memory deficit evidenced by a significant reduction in novel arm entry, time spent in the novel arm, alternation, time exploring novel and familiar objects, and discrimination index. These findings were accompanied by a marked distortion in the histology of the prefrontal cortex, and a decline in serum dopamine level and pyramidal neurons. In addition, ovariectomy and lead exposure induced metabolic disruption (as depicted by a marked rise in lactate level and lactate dehydrogenase and creatinine kinase activities), oxidative stress (evidenced by a significant increase in MDA level, and decrease in GSH level, and SOD and catalase activities), inflammation (as shown by significant upregulation of myeloperoxidase activity, and TNF-α and IL-1β), and apoptosis (evidenced by a rise in caspase 3 activity) of the prefrontal cortex. The observed biochemical and histological perturbations were attenuated by HRT.</div></div><div><h3>Conclusions</h3><div>This study revealed that HRT attenuated ovariectomy and lead-exposure-induced spatial memory deficit and pyramidal neurodegeneration by suppressing oxidative stress, inflammation, and apoptosis of the prefrontal cortex.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100200"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental transfer of tofacitinib in the ex vivo dual-side human placenta perfusion model","authors":"Gaby A.M. Eliesen ,&nbsp;Milou Fransen ,&nbsp;Hedwig van Hove ,&nbsp;Petra H.H. van den Broek ,&nbsp;Rick Greupink","doi":"10.1016/j.crtox.2024.100149","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100149","url":null,"abstract":"<div><p>Tofacitinib is a small molecule Janus kinase (JAK) inhibitor, introduced to the European market in 2017, for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. In the treatment of women with autoimmune diseases, pregnancy is a relevant issue, as such diseases typically affect women in their reproductive years. Currently, there is limited data on the use of tofacitinib during pregnancy. To estimate the extent of placental transfer in the absence of clinical data, we conducted <em>ex vivo</em> dual-side perfused human placental cotyledon perfusions. Term placentas were perfused for 180 min with tofacitinib (100 nM, added to the maternal circuit) in a closed-closed configuration. At the end of the perfusions, drug concentrations in the maternal and fetal reservoirs were near equilibrium, at 35.6 ± 5.5 and 24.8 ± 4.7 nM, respectively. Transfer of tofacitinib was similar to that observed for the passive diffusion marker antipyrine (100 µg/mL, added to the maternal reservoir). Final antipyrine maternal and fetal concentrations amounted to 36.9 ± 3.0 and 36.7 ± 1.3 µg/mL, respectively. In conclusion, in the <em>ex vivo</em> perfused placenta tofacitinib traverses the placental barrier rapidly and extensively. This suggests that substantial fetal tofacitinib exposure will take place after maternal drug dosing.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100149"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000021/pdfft?md5=750bbc6c92fbedeaeb8bafe931bcf4db&pid=1-s2.0-S2666027X24000021-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139419305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D human stem-cell-derived neuronal spheroids for in vitro neurotoxicity testing of methylglyoxal, highly reactive glycolysis byproduct and potent glycating agent","authors":"Teresa Coccini ,&nbsp;Francesca Caloni ,&nbsp;Luciana Alessandra Russo ,&nbsp;Laura Villani ,&nbsp;Davide Lonati ,&nbsp;Uliana De Simone","doi":"10.1016/j.crtox.2024.100176","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100176","url":null,"abstract":"<div><p>Human-derived three-dimensional (3D) <em>in vitro</em> models are advanced <em>human cell-based</em> model for their complexity, relevance and application in toxicity testing. Intracellular accumulation of methylglyoxal (MGO), the most potent glycating agent in humans, mainly generated as a by-product of glycolysis, is associated with age-related diseases including neurodegenerative disorders.</p><p>In our study, 3D human stem-cell-derived neuronal spheroids were set up and applied to evaluate cytotoxic effects after short-term (5 to 48 h) treatments with different MGO concentrations, including low levels, taking into consideration several biochemical endpoints.</p><p>In MGO-treated neurospheroids, reduced cell growth proliferation and decreased cell viability occurred early from 5-10 μM, and their compactness diminished starting from 100 μM, apparently without affecting spheroid size. MGO markedly caused loss of the neuronal markers MAP-2 and NSE from 10-50 μM, decreased the detoxifying Glo1 enzyme from 50 μM, and activated NF-kB by nuclear translocation.</p><p>The cytochemical evaluation of the 3D sections showed the presence of necrotic cells with loss of nuclei. Apoptotic cells were observed from 50 μM MGO after 48 h, and from 100 μM after 24 h. MGO (50–10 µM) also induced modifications of the cell–cell and cell-ECM interactions. These effects worsened at the higher concentrations (300–500 µM).</p><p>In 3D neuronal spheroids, MGO tested concentrations comparable to human samples levels measured in MGO-associated diseases, altered neuronal key signalling endpoints relevant for the pathogenesis of neurodegenerative diseases and aging. The findings also demonstrated that the use of 3D neuronal spheroids of human origin can be useful in a strategy <em>in vitro</em> for testing MGO and other dicarbonyls evaluation.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100176"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X2400029X/pdfft?md5=215eca89a24ba4180c3d12b699dc970d&pid=1-s2.0-S2666027X2400029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using targeted fetal rat testis genomic and endocrine alterations to predict the effects of a phthalate mixture on the male reproductive tract","authors":"L. Earl Gray Jr ,&nbsp;Christy S. Lambright ,&nbsp;Nicola Evans ,&nbsp;Jermaine Ford ,&nbsp;Justin M. Conley","doi":"10.1016/j.crtox.2024.100180","DOIUrl":"10.1016/j.crtox.2024.100180","url":null,"abstract":"<div><p>Administration of phthalates <em>in utero</em> disrupts gene expression and hormone levels in the fetal rat testis, which are key events in an Adverse Outcome Pathway (AOP) for the Phthalate Syndrome. These measures can be used to predict the postnatal adverse effects of phthalate esters (PEs) on male rat sexual differentiation. Here, pregnant rats were exposed to dibutyl (DBP)- and diisononyl (DINP) phthalate on gestational days 14 to 18 individually and as a mixture (DBP,250 mg/kg/d; DINP, 750 mg/kg/d; and DBP 250 mg/kg/d plus DINP 750 mg/kg/d). We found that each PE reduced testosterone production (T Prod) and related gene transcripts by about 50 % and that they acted in a dose additive manner, reducing T Prod and gene expression by 75 % as a mixture. Based upon effects on T Prod, DINP was 0.33 times as potent as DBP and thus the DBP + DINP mixture was predicted to be equivalent to 500 mg DBP/kg/d.</p><p>Logistic regression models of T Prod predicted that the adverse effects of the DBP + DINP mixture group versus the DBP and DINP individual treatments would reduce anogenital distance (AGD) by 27 % versus 10 %, increase hypospadias in 18 % versus &lt; 1 %, induce epididymal agenesis in 46 % versus 10 %, and increase areolae/nipples in 4.8 % versus &lt; 0.1 % of the, respectively. These predictions were highly consistent with effects from previously published dose response studies on the male reproductive effects of DBP. In summary, these results support the use of this New Approach Method to predict the detrimental effects of PEs and PE mixtures, replacing or reducing the need to run long-term, resource and animal use intensive extended one-generation reproduction studies for this class of chemicals.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100180"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000331/pdfft?md5=0c74927333f72ddbcf93a0ec39b540c1&pid=1-s2.0-S2666027X24000331-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis as an emerging target in sickle cell disease","authors":"Vitor Fortuna ,&nbsp;Jaqueline Lima ,&nbsp;Gabriel F. Oliveira ,&nbsp;Yasmin S. Oliveira ,&nbsp;Bruk Getachew ,&nbsp;Sergei Nekhai ,&nbsp;Michael Aschner ,&nbsp;Yousef Tizabi","doi":"10.1016/j.crtox.2024.100181","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100181","url":null,"abstract":"<div><p>Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100181"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000343/pdfft?md5=1490b17318a14897e021de212f1f903c&pid=1-s2.0-S2666027X24000343-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-derived and Patient-Derived Organoids: Applications and challenges in scalability and reproducibility as pre-clinical models","authors":"Elisa Heinzelmann ,&nbsp;Francesco Piraino ,&nbsp;Mariana Costa ,&nbsp;Aline Roch ,&nbsp;Maxim Norkin ,&nbsp;Virginie Garnier ,&nbsp;Krisztian Homicsko ,&nbsp;Nathalie Brandenberg","doi":"10.1016/j.crtox.2024.100197","DOIUrl":"10.1016/j.crtox.2024.100197","url":null,"abstract":"<div><div>Recent advancements in stem cell technology have led to the development of organoids – three-dimensional (3D) cell cultures that closely mimic the structural and functional characteristics of human organs. These organoids represent a significant improvement over traditional two-dimensional (2D) cell cultures by preserving native tissue architecture and cellular interactions critical for physiological relevance.</div><div>This review provides a comprehensive comparison between two main types of organoids: induced Pluripotent Stem Cell (iPSC)-derived and Adult Stem Cell (ASC)-derived (also known as Patient-Derived Organoids, PDOs). iPSC-derived organoids, derived from reprogrammed cells, exhibit remarkable plasticity, and can model a wide range of tissues and developmental stages. They are particularly valuable for studying early human development, genetic disorders, and complex diseases. However, challenges such as prolonged differentiation protocols and variability in maturation levels remain significant hurdles. In contrast, ASC-derived organoids, generated directly from patient tissues, faithfully recapitulate tissue-specific characteristics and disease phenotypes. This fidelity makes them indispensable for personalized medicine applications, including drug screening, disease modeling, and understanding individualized treatment responses.</div><div>The review highlights the unique advantages and limitations of each organoid type, emphasizing their roles in advancing biomedical research and drug discovery. It addresses key challenges in organoid technology, such as scalability, reproducibility, and the need for standardized culture protocols. Furthermore, it explores recent innovations in scaffold-guided organoid engineering and the integration of organoids with advanced technologies like artificial intelligence and high-throughput screening.</div><div>The integration of organoids with cutting-edge technologies holds promise for enhancing their utility in modeling complex human diseases and accelerating drug discovery and development. By providing more physiologically relevant models of human organs, organoid technology is poised to revolutionize biomedical research, offering new insights into disease mechanisms and personalized therapeutic strategies.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100197"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early prediction of cognitive impairment in adults aged 20 years and older using machine learning and biomarkers of heavy metal exposure","authors":"Ali Nabavi ,&nbsp;Farimah Safari ,&nbsp;Mohammad Kashkooli ,&nbsp;Sara Sadat Nabavizadeh ,&nbsp;Hossein Molavi Vardanjani","doi":"10.1016/j.crtox.2024.100198","DOIUrl":"10.1016/j.crtox.2024.100198","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment poses a growing health challenge as populations age. Heavy metals are implicated as environmental risk factors, but their role is not fully understood. Machine learning can integrate multi-factorial data to predict cognitive outcomes.</div></div><div><h3>Objective</h3><div>To develop and validate machine learning models for early prediction of cognitive impairment risk using demographics, clinical factors, and biomarkers of heavy metal exposure.</div></div><div><h3>Method</h3><div>A retrospective analysis was conducted using 2011–2014 NHANES data. Participants aged ≥ 20 underwent cognitive testing. Variables included demographics, medical history, lifestyle factors, and blood and urine levels of lead, cadmium, manganese, and other metals. Machine learning algorithms were trained on 90 % of data and evaluated on 10 %. Performance was assessed using metrics like accuracy, AUC, and sensitivity.</div></div><div><h3>Result</h3><div>A final sample of 2,933 participants was analyzed. The stacking ensemble model achieved the best performance with an AUC of 0.778 for test data, sensitivity of 0.879. Important predictors included age, gender, hypertension, education, urinary cadmium and blood manganese levels.</div></div><div><h3>Conclusion</h3><div>Machine learning can effectively predict cognitive impairment risk using comprehensive clinical and exposure data. Incorporating heavy metal biomarkers enhanced prediction and provided insights into environmental contributions to cognitive decline. Prospective studies are needed to validate models over time.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100198"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARγ activation ameliorates PM2.5-induced renal tubular injury by inhibiting ferroptosis and epithelial–mesenchymal transition","authors":"Chien-Hung Lin ,&nbsp;Wen-Sheng Liu ,&nbsp;Chuan Wan ,&nbsp;Hsin-Hui Wang","doi":"10.1016/j.crtox.2024.100189","DOIUrl":"10.1016/j.crtox.2024.100189","url":null,"abstract":"<div><p>Exposure to fine particulate matter (PM2.5) has been associated with the development and progression of renal disease. Peroxisome proliferator-activated receptor gamma (PPARγ), a key transcription factor involved in inflammation as well as lipid and glucose metabolism, helps maintain the integrity of tubular epithelial cells. However, the precise role of PPARγ in PM2.5-induced tubular injury remains unclear. In this study, we investigated the regulatory effects of PPARγ on PM2.5-induced ferroptotic stress and epithelial–mesenchymal transition (EMT) in tubular (HK-2) cells. We found that downregulation of PPARγ expression was correlated with EMT in PM2.5-exposed cells. Pretreatment with the PPARγ agonist 15d-PGJ2 protected the cells from EMT by reducing ferroptotic stress, whereas that with the PPARγ antagonist GW9662 promoted EMT. Furthermore, pretreatment with ferrostatin-1 (Fer-1) significantly prevented PM2.5-induced EMT and downregulation of PPARγ expression. Notably, overexpression of PPARγ blocked PM2.5-induced downregulation of E-cadherin and GPX4 expression and upregulation of α-SMA expression. This study highlights the complex associations of PPARγ with ferroptosis and EMT in PM2.5-exposed tubular cells. Our findings suggest that PPARγ activation confers protection against PM2.5-induced renal injury.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100189"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000422/pdfft?md5=902c1b7607a020f8948c7daf50b6eb1b&pid=1-s2.0-S2666027X24000422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer","authors":"Qian Li ,&nbsp;Shujing Zhang ,&nbsp;Qinghong Zhou ,&nbsp;Chenxi Gu ,&nbsp;Yinghua Liu ,&nbsp;Jing Zhang ,&nbsp;Jingshu Zhang","doi":"10.1016/j.crtox.2024.100196","DOIUrl":"10.1016/j.crtox.2024.100196","url":null,"abstract":"<div><div>This study aimed to evaluate the preventive efficacy of tocotrienol in inhibiting the nuclear factor-kappa B (NF-κB) mediated inflammation pathways in colorectal cancer. We utilized the azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to induce colitis-associated colorectal cancer (CAC) mice model. In generating a CAC model, mice were intraperitoneally injected with AOM at a concentration of 10 mg/kg body weight. Seven days after the AOM injection, mice drinking water containing 3 % DSS for 1 week, followed by a 2-week period of regular water. This cycle of DSS treatment (1-week 3 % DSS+2-week water) was repeated for two additional cycles. Mice were randomly divided into five groups (n = 20/group), including Blank group, Model group, three different dosages tocotrienol groups (Low dose group [50 mg/kg], Medium dose group [75 mg/kg], and High dose group [100 mg/kg]). The protective effects of tocotrienol were assessed using histological, flow cytometry, western blot and mouse Luminex assay. Compared with the blank group, expressions of toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6), NF-κB, Interleukin (IL)-6 and tumor necrosis factor (TNF) −α were increased in model group, while IL-4 and IL-10 were decreased in model group (<em>P</em>&lt;0.05). Tocotrienol prevented carcinogenesis and decreased the IL-6, TNF-α, MyD88, TLR4, TRAF-6 and NF-κB expression levels, compared with the model group (<em>P</em>&lt;0.05). Compared with the model group, the expression of IL-10 was increased in medium dose group and high dose group (<em>P</em>&lt;0.05). The protective effects of tocotrienol may be related to the inhibition of TLR4 /MyD88 /NF-κB mediated inflammatory signaling pathways. Therefore, the use of tocotrienol can improve the abnormal expression of cytokines in a mouse model of colorectal cancer and inhibit the occurrence and development of colorectal cancer.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100196"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight on cytotoxic NHC gold(I) halide complexes evaluated in multifaceted culture systems","authors":"Vincenza De Gregorio ,&nbsp;Alessandra La Pietra ,&nbsp;Andrea Candela ,&nbsp;Carlo Oliviero ,&nbsp;Ida Ferrandino ,&nbsp;Diego Tesauro","doi":"10.1016/j.crtox.2024.100174","DOIUrl":"10.1016/j.crtox.2024.100174","url":null,"abstract":"<div><p>Gold complexes can be a useful system in the fight against cancer. Although many studies have been carried out on in vitro 2D cell culture models embryotoxic assays are particularly lacking. Embryotoxicity and DNA damage are critical concerns in drug development. In this study, the effects of a new N-Heterocyclic carbene (NHC)-Au compound (Bromo[1,3-di-4-methoxybenzyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]gold(I)) at different concentrations were explored using multifaceted approach, encompassing 2D cancer cell cultures, <em>in vivo</em> zebrafish and in vitro bovine models, and compared with a consolidated similar complex (Bromo[1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]gold(I)). The results obtained from 2D cancer cell cultures revealed concentration-dependent effects of the gold compounds by estimating the cytotoxicity with MTT assay and cellular damage as indicated by LDH release. Selected concentrations of gold complexes demonstrated no adverse effects on zebrafish embryo development. However, in bovine embryos, these same concentrations led to significant impairments in the early developmental stages, triggering cell apoptosis and reducing blastocyst competence. These findings underscore the importance of evaluating drug effects across different model systems to comprehensively assess their safety and potential impact on embryonic development.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100174"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000276/pdfft?md5=734ebceb816cc928e98d56c5ae0b24b1&pid=1-s2.0-S2666027X24000276-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141143905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}