{"title":"Antiurolithiatic effect of triptonide in ethylene glycol-induced urolithiasis in rats.","authors":"Qiang Wang, Jinghong Zhang, Xiaosong Yin, Tongwei Liu, Chuangui Li, Haibo Yuan, Ding Li","doi":"10.1080/15376516.2024.2364882","DOIUrl":"10.1080/15376516.2024.2364882","url":null,"abstract":"<p><p>Urolithiasis is one of the most prevalent benign urological disorders globally with a high incidence rate. Male Sprague-Dawley rats were chemically induced to have urolithiasis and treated with triptonide and the standard antiurolithic drug cystone. Kidney weight was measured to detect calculi formation, and urinary parameters such as pH, 24-h urine volume, and protein content were measured to analyze the urolithiasis induction in rats. The inorganic ions, organic solutes, antioxidant levels, and inflammatory cytokines were measured in the experimental rats. Triptonide treatment significantly modulated the urinary pH, decreased the protein concentration, and increased the urinary outflow in urolithiasis induced rats. It also significantly decreased the urinary excretion of calcium and phosphorous and increased the excretion of magnesium, potassium, sodium, creatinine, and uric acid. SOD, CAT, and GPx levels were increased in triptonide-treated rats, and it significantly reduced the MDA levels. Triptonide treatment also decreased the levels of inflammatory cytokines and prevented the renal tissue from inflammation. To conclude, our results prove that triptonide significantly prevents calculi formation and protects renal tissue from urolithiasis-induced damage in rats. Further studies may prove triptonide a potent alternative to currently available antiurolithic drugs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"926-935"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451545","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}
{"title":"Unveiling the impact of estrogen exposure on ovarian cancer: A comprehensive risk model and immune landscape analysis.","authors":"Zhongna Yu,Weili Yang,Qinwei Zhang,Mengyu Zheng","doi":"10.1080/15376516.2024.2402865","DOIUrl":"https://doi.org/10.1080/15376516.2024.2402865","url":null,"abstract":"This study examines the impact of estrogenic compounds like bisphenol A (BPA), estradiol (E2), and zearalenone (ZEA) on human ovarian cancer, focusing on constructing a risk model, conducting Gene Set Variation Analysis (GSVA), and evaluating immune infiltration. Differential gene expression analysis identified 980 shared differentially expressed genes (DEGs) in human ovarian cells exposed to BPA, E2, and ZEA, indicating disruptions in ribosome biogenesis and RNA processing. Using the Cancer Genome Atlas Ovarian Cancer (TCGA-OV) dataset, a least absolute shrinkage and selection operator (LASSO)-based risk model was developed incorporating prognostic genes 4-Hydroxyphenylpyruvate Dioxygenase Like (HPDL), Thy-1 Cell Surface Antigen (THY1), and Peptidase Inhibitor 3 (PI3). This model effectively stratified ovarian cancer patients into high-risk and low-risk categories, showing significant differences in overall survival, disease-specific survival, and progression-free survival. GSVA analysis linked HPDL expression to pathways related to the cell cycle, DNA damage, and repair, while THY1 and PI3 were associated with apoptosis, hypoxia, and proliferation pathways. Immune infiltration analysis revealed distinct immune cell profiles for high and low expression groups of HPDL, THY1, and PI3, indicating their influence on the tumor microenvironment. The findings demonstrate that estrogenic compounds significantly alter gene expression and oncogenic pathways in ovarian cancer. The risk model integrating HPDL, THY1, and PI3 offers a strong prognostic tool, with GSVA and immune infiltration analyses providing insights into the interplay between these genes and the tumor microenvironment, suggesting potential targets for personalized therapies.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"180 1","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214524","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}
Samudra P Banik,Pawan Kumar,Pijush Basak,Apurva Goel,Sunny E Ohia,Manashi Bagchi,Sanjoy Chakraborty,Arijit Kundu,Debasis Bagchi
{"title":"A critical insight into the physicochemical stability of macular carotenoids with respect to their industrial production, safety profile, targeted tissue delivery, and bioavailability.","authors":"Samudra P Banik,Pawan Kumar,Pijush Basak,Apurva Goel,Sunny E Ohia,Manashi Bagchi,Sanjoy Chakraborty,Arijit Kundu,Debasis Bagchi","doi":"10.1080/15376516.2024.2401924","DOIUrl":"https://doi.org/10.1080/15376516.2024.2401924","url":null,"abstract":"Lutein, zeaxanthin and mesozeaxanthin, collectively termed as macular pigments, are key carotenoids integral to optimized central vision of the eye. Therefore, nutraceuticals and functional foods have been developed commercially using carotenoid rich flowers such as marigold and calendula or single celled photosynthetic algae such as the Dunaliella. Industrial formulation of such products enriched in macular pigments have often suffered from serious bottlenecks in stability, delivery and bioavailability. The two chief factors largely responsible for decreasing the shelf-life have been solubility and oxidation of these pigments owing to their strong lipophilic nature and presence of conjugated double bonds. In this regard, oil-based formulations have often been found to be more suitable than powder-based formulations in terms of shelf life and targeted delivery. In some cases, addition of phenolic acids in the formulations have also augmented the product value by enhancing micellization. In this regard, a novel proprietary formulation of these pigments has been developed in our laboratory utilizing marigold extracts in a colloidal solution of extra virgin olive oil and canola oil fortified with antioxidants like thyme oil, tocopherol and ascorbyl palmitate. This review article presents an updated insight on the stability and bioavailability of industrially manufactured macular carotenoids together with their safety and solubility issues.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"59 1","pages":"1-26"},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214526","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}
Derya Cansız, Gökhan Özokan, Abdulkerim Bilginer, Semanur Işıkoğlu, Zülal Mızrak, İsmail Ünal, Merih Beler, A Ata Alturfan, Ebru Emekli-Alturfan
{"title":"Effects of benzoic acid synthesized from <i>Cinnamomum cassia</i> by green chemistry on valproic acid-induced neurotoxicity in zebrafish embryos.","authors":"Derya Cansız, Gökhan Özokan, Abdulkerim Bilginer, Semanur Işıkoğlu, Zülal Mızrak, İsmail Ünal, Merih Beler, A Ata Alturfan, Ebru Emekli-Alturfan","doi":"10.1080/15376516.2024.2364899","DOIUrl":"10.1080/15376516.2024.2364899","url":null,"abstract":"<p><p>Benzoic acid, the most basic aromatic carboxylic acid, is produced industrially and used in cosmetic, hygiene, and pharmaceutical items as a flavoring ingredient and/or preservative. The significance of sodium benzoate, a metabolite of cinnamon, used as a food preservative and FDA-approved medication to treat urea cycle abnormalities in humans, has been shown to raise the levels of neurotrophic factors. Valproic acid (VPA), a commonly used anti-epileptic and mood-stabilizing medication, causes behavioral and intellectual problems and is a commonly used agent to induce animal model for autism. Aim of this study is to determine the effects of benzoic acid synthesized from <i>Cinnamomum Cassia</i> by green chemistry method on gene expressions related to autism development in case of VPA toxicity. Zebrafish embryos were exposed to low and high doses of benzoic acid for 72 h post-fertilization. Locomotor activities were determined. Acetylcholinesterase (AchE), lipid peroxidation, nitric oxide (NO), sialic acid (SA), glutathione (GSH)-S-transferase, catalase (CAT), and superoxide dismutase (SOD) activities were determined spectrophotometrically. <i>eif4b</i>, <i>adsl</i>, and <i>shank3a</i> expressions were determined by RT-PCR as autism-related genes. Although high-dose benzoic acid inhibited locomotor activity, benzoic acid at both doses ameliorated VPA-induced disruption in oxidant-antioxidant balance and inflammation in zebrafish embryos and was effective in improving the impaired expression of autism-related genes.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"833-843"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421020","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}
{"title":"<i>In-silico</i> green toxicology approach toward discovering safer ligands for development of safe-by-design metal-organic frameworks.","authors":"Reyhane Khezri, Seyed Jamaleddin Shahtaheri, Elahe Khezri, Mahdi Niknam Shahrak, Monireh Khadem","doi":"10.1080/15376516.2024.2353364","DOIUrl":"10.1080/15376516.2024.2353364","url":null,"abstract":"<p><p>A vast variety of chemical compounds have been fabricated and commercialized, they not only result in industrial exposure during manufacturing and usage, but also have environmental impacts throughout their whole life cycle. Consequently, attempts to assess the risk of chemicals in terms of toxicology have never ceased. <i>In-silico</i> toxicology, also known as predictive toxicology, has advanced significantly over the last decade as a result of the drawbacks of experimental investigations. In this study, ProTox-III was applied to predict the toxicity of the ligands used for metal-organic framework (MOF) design and synthesis. Initially, 35 ligands, that have been frequently utilized for MOF synthesis and fabrication, were selected. Subsequently, canonical simplified molecular-input line-entry system (SMILES) of ligands were extracted from the PUBCHEM database and inserted into the ProTox-III online server. Ultimately, webserver outputs including LD<sub>50</sub> and the probability of toxicological endpoints (cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, and ecotoxicity) were obtained and organized. According to retrieved LD<sub>50</sub> data, the safest ligand was 5-hydroxyisophthalic. In contrast, the most hazardous ligand was 5-chlorobenzimidazole, with an LD<sub>50</sub> of 8 mg/kg. Among evaluated endpoints, ecotoxicity was the most active and was detected in several imidazolate ligands. This data can open new horizons in design and development of green MOFs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"821-832"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899597","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}
Mei Jing Piao, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Jin Won Hyun
{"title":"Silver nanoparticle-induced cell damage via impaired mtROS-JNK/MnSOD signaling pathway.","authors":"Mei Jing Piao, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Jin Won Hyun","doi":"10.1080/15376516.2024.2350595","DOIUrl":"10.1080/15376516.2024.2350595","url":null,"abstract":"<p><p>This study investigated the mechanism of silver nanoparticle (AgNP) cytotoxicity from a mitochondrial perspective. The effect of AgNP on manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, against oxidative stress has not been studied in detail. We demonstrated that AgNP decreased MnSOD mRNA level, protein expression, and activity in human Chang liver cells in a time-dependent manner. AgNP induced the production of mitochondrial reactive oxygen species (mtROS), particularly superoxide anion. AgNP was found to increase mitochondrial calcium level and disrupt mitochondrial function, leading to reduced ATP level, succinate dehydrogenase activity, and mitochondrial permeability. AgNP induced cytochrome c release from the mitochondria into the cytoplasm, attenuated the expression of the anti-apoptotic proteins phospho Bcl-2 and Mcl-1, and induced the expression of the pro-apoptotic proteins Bim and Bax. In addition, c-Jun N-terminal kinase (JNK) phosphorylation was significantly increased by AgNP. Treatment with elamipretide (a mitochondria-targeted antioxidant) and SP600125 (a JNK inhibitor) showed the involvement of MnSOD and JNK in these processes. These results indicated that AgNP damaged human Chang liver cells by destroying mitochondrial function through the accumulation of mtROS.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"803-812"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912754","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}
Nevine Khairy Elkady, Abrar Roshdy Abouelkheir, Sherien S Ghaleb, Olfat Gamil Shaker, Heba Abd ElMonem Ibrahim, Eman Mohamed Ibraheim Moawad, Asmaa Mohammad Moawad
{"title":"Evaluating the possible genotoxicity of nanoaluminum incorporated in human vaccines and the potential protective role of nanocurcumin: an <i>in vivo</i> study.","authors":"Nevine Khairy Elkady, Abrar Roshdy Abouelkheir, Sherien S Ghaleb, Olfat Gamil Shaker, Heba Abd ElMonem Ibrahim, Eman Mohamed Ibraheim Moawad, Asmaa Mohammad Moawad","doi":"10.1080/15376516.2024.2352736","DOIUrl":"10.1080/15376516.2024.2352736","url":null,"abstract":"<p><p>For nearly 90 years, aluminum (Al) salts have been utilized as vaccination adjuvants. Nevertheless, there is a risk of adverse effects associated with the amount of nanoaluminum used in various national pediatric immunization regimens. This study aimed to investigate the possible genotoxic effects of nanoaluminum incorporated in human vaccines on the brains of newborn albino rats and whether nanocurcumin has a potential protective effect against this toxicity. Fifty newborn albino rats were randomly assigned to 5 groups, with 10 in each group. Groups 1 and 2 received \"high\" and \"low\" Al injections corresponding to either the American or Scandinavian pediatric immunization schedules, respectively, as opposed to the control rats (group 5) that received saline injections. Groups 3 and 4 received the same regimens as groups 1 and 2 in addition to oral nanocurcumin. The expression of both the cell breakdown gene tumor protein (P53) and the cell stress gene uncoupling protein 2 (UCP2) was significantly greater in groups 1 and 2 than in group 5. Groups 1 and 2 exhibited severe DNA fragmentation, which was observed as DNA laddering. Nanocurcumin significantly reduced the expression of the P53 and UCP2 genes in groups 3 and 4, with very low or undetectable DNA laddering in both groups. Vaccination with nanoaluminum adjuvants can cause genotoxic effects, which can be mediated by the inflammatory response and oxidative stress, and nanocurcumin can protect against these toxic effects through the modulation of oxidative stress regulators and gene expression.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"813-820"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892526","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}
{"title":"Assessment of TGx-DDI genes for genotoxicity in a comprehensive panel of chemicals.","authors":"A Rasim Barutcu","doi":"10.1080/15376516.2024.2335966","DOIUrl":"10.1080/15376516.2024.2335966","url":null,"abstract":"<p><strong>Background: </strong>The TGx-DDI biomarker identifies transcripts specifically induced by primary DNA damage. Profiling similarity of TGx-DDI signatures can allow clustering compounds by genotoxic mechanism. This transcriptomics-based approach complements conventional toxicology testing by enhancing mechanistic resolution.</p><p><strong>Methods: </strong>Unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding (tSNE) were utilized to assess similarity of publicly-available per- and polyfluoroalkyl substances (PFAS) and ToxCast chemicals based on TGx-DDI modulation. TempO-seq transcriptomic data after highest chemical concentrations were analyzed.</p><p><strong>Results: </strong>Clustering discriminated between genotoxic and non-genotoxic compounds while drawing similarity among chemicals with shared mechanisms. PFAS largely clustered distinctly from classical mutagens. However, dynamic range across PFAS types and durations indicated variable potential for DNA damage. tSNE visualization reinforced phenotypic groupings, with genotoxins clustering separately from non-DNA damaging agents.</p><p><strong>Discussion: </strong>Unsupervised learning approaches applied to TGx-DDI profiles effectively categorizes chemical genotoxicity potential, aiding elucidation of biological response pathways. This transcriptomics-based strategy gives further insight into the role and effect of individual TGx-DDI biomarker genes and complements existing assays by enhancing mechanistic resolution. Overall, TGx-DDI biomarker profiling holds promise for predictive safety screening.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"761-767"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307026","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}
{"title":"Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats.","authors":"Anuradha Mangla, Poonam Goswami, Bhaskar Sharma, Suramya Suramya, Garima Jindal, Mehjbeen Javed, Mohd Anas Saifi, Suhel Parvez, Tapas Chandra Nag, Sheikh Raisuddin","doi":"10.1080/15376516.2024.2349538","DOIUrl":"10.1080/15376516.2024.2349538","url":null,"abstract":"<p><p>Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L <i>via</i> drinking water for 90 days). Four groups were taken in this study - Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor- kappa B (NF-КB) in the brain. Obesity also caused significant (<i>p</i> < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (<i>p</i> < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"781-794"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860483","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}