Toxicology Mechanisms and Methods最新文献

{"title":"Reactions of deoxyribonucleotide bases with sulfooxymethyl or halomethyl polycyclic aromatic hydrocarbons induce unwinding of DNA supercoils.","authors":"Andreas F Lehner","doi":"10.1080/15376516.2023.2297836","DOIUrl":"10.1080/15376516.2023.2297836","url":null,"abstract":"<p><p>Torsional stress in double-stranded DNA enables and regulates facets of chromosomal metabolism, replication, and transcription and requires regulatory enzymatic systems including topoisomerases and histone methyltransferases. As such, this machinery may be subject to deleterious effects from reactive mutagens, including ones from carcinogenic polycyclic aromatic hydrocarbon (PAH) adduct formation with DNA. Supercoiled plasmid DNA was investigated for its torsional responses to adducts formed <i>in vitro</i> from PAH benzylic carbocation reactive intermediates created spontaneously by release of leaving groups. PAH sulfate esters were found to (1) unwind DNA in a concentration dependent manner, and (2) provide maximum unwinding in a pattern consistent with known carcinogenicities of the parent PAHs, that is, 6-methylbenzo[a]pyrene > 7,12-methylbenz[a]anthracene > 3-methylcholanthrene > 9-methylanthracene > 7-methylbenz[a]anthracene > 1-methylpyrene. Supercoil unwinding was demonstrated to be dependent on the presence of sulfate or chloride leaving groups such that reactive carbocations were generated <i>in situ</i> by hydrolysis. <i>In silico</i> modeling of intercalative complex topology showed PAH benzylic carbocation reactive functional groups in alignment with target nucleophiles on guanine bases in a 5'-dCdG-3' pocket in agreement with known formation of nucleotide adducts. Inhibitory or modulatory effects on PAH-induced supercoil unwinding were seen with ascorbic acid and an experimental antineoplastic agent Antineoplaston A10 in agreement with their known anticarcinogenic properties. In summary, the reactive PAH intermediates studied here undoubtedly participate in well-known mutational mechanisms such as frameshifts and apurinic site generation. However, they are also capable of random disruption of chromosomal supercoiling in a manner consistent with the known carcinogenicities of the parent compounds, and this mechanism may represent an additional detrimental motif worthy of further study for a more complete understanding of chemical carcinogenicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"423-443"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138831635","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":"Investigating the progression of preeclampsia through a comprehensive analysis of genes associated with per- and polyfluoroalkyl substances.","authors":"Qiuyan Ge, Ju Zhao, Fujuan Qu","doi":"10.1080/15376516.2023.2299485","DOIUrl":"10.1080/15376516.2023.2299485","url":null,"abstract":"<p><p>Per- and Polyfluoroalkyl Substances (PFAS) are synthetic chemicals utilized in the production of various products that possess water and dirt-repellent properties. Exposure to PFAS has been linked to numerous diseases, such as cancer and preeclampsia (PE). However, whether PFAS contributes to the advancement of PE remains uncertain. In this study, we conducted an extensive bioinformatics analysis using the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) databases, leading us to discover a connection between PE and four specific PFAS. Moreover, further examination revealed that six genes associated with PFAS exhibited significant diagnostic potential for individuals with PE. By employing receiver operating characteristic (ROC) curves, our PFAS-related gene-based nomogram model demonstrated outstanding predictive efficacy for diagnosing PE. Immune infiltration analysis showed that six PFAS-related genes were significantly associated with the level of immune cell infiltration. The expression of PFAS-related genes in PE patients was confirmed by collecting clinical samples. This research has offered fresh perspectives on comprehending the impact of PFAS on PE, drawing attention to the connection between environmental factors and the risks and development of PE.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"444-453"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080932","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":"Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis.","authors":"Gokhan Akcakavak, Filiz Kazak, Ozhan Karatas, Halil Alakus, Ibrahim Alakus, Omer Kirgiz, Zeynep Celik, Mehmet Zeki Yilmaz Deveci, Ozgur Ozdemir, Mehmet Tuzcu","doi":"10.1080/15376516.2023.2297234","DOIUrl":"10.1080/15376516.2023.2297234","url":null,"abstract":"<p><p>Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1β), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), Caspase-3, 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1β, iNOS, TNF-α, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67-fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"413-422"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806321","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":"Alcohol-induced hormonal and metabolic alterations in plasma and erythrocytes-a gender-based study.","authors":"Daisy Kunnathuparambil Lonappan, Gouthami Kuruvalli, Althaf Hussain Shaik, Ananda Vardhan Hebbani, Hymavathi Reddyvari, Vaddi Damodara Reddy, Veeraraghavan Vadamalai","doi":"10.1080/15376516.2023.2290071","DOIUrl":"10.1080/15376516.2023.2290071","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to understand the gender-specific alcohol-induced biochemical changes and TBARS association with the endocrine system.</p><p><strong>Methods: </strong>Human male and female subjects ranging from 35 ± 10 years old with an 8-10-year drinking history were included in the study.</p><p><strong>Results: </strong>The results demonstrated that testosterone levels were lower in male alcoholics and higher in female alcoholics, as well as higher estrogen and cortisol levels in both genders. In addition, we found lower T3, T4, and thyroid-stimulating hormone (TSH) levels in alcoholics of both sexes. Furthermore, plasma TBARS, protein carbonyls, nitrite, and nitrate levels increased significantly with concomitant decrease in reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in both male and female alcoholics. Furthermore, erythrocyte lysate nitrite and nitrate levels membrane total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio with lower total membrane proteins in both genders of alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed increased density of band 3, protein 4.1, 4.2, 4.9 and glycophorins, whereas decreases in spectrin (α and β) were observed in both genders of alcoholics. Besides, alcoholics of both sexes had a lower ability to resist osmotic hemolysis. Plasma TBARS was negatively correlated with testosterone, TSH, T3 and T4 in male alcoholics, moreover, estradiol and cortisol were positively correlated in males and females respectively.</p><p><strong>Conclusion: </strong>Female alcoholics may be more susceptible to osmotic hemolysis due to increased erythrocyte membrane lipid peroxidation with decreased antioxidant status, which results in an altered membrane C/P ratio and membrane protein composition.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"350-358"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462830","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":"Lauric acid attenuates hepato-metabolic complications and molecular alterations in high-fat diet-induced nonalcoholic fatty liver disease in rats.","authors":"Ahmed A Sedik, Rania Elgohary, Eman Khalifa, Wagdy K B Khalil, Heba I Shafey, Mohamed B Shalaby, Mona S O Gouida, Yasmin M Tag","doi":"10.1080/15376516.2023.2301344","DOIUrl":"10.1080/15376516.2023.2301344","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver illness characterized by increase of lipid content in the liver. This study investigated the role of lauric acid to treat NAFLD in male adult Sprague Dawley rats. In this study, to induce NAFLD in the rats, a high-fat diet (HFD) was administered for eight consecutive weeks. Lauric acid groups received lauric acid (250 and 500 mg/kg; orally), concurrently with HFD for eight consecutive weeks. Lauric acid could ameliorate the serum levels of TG, TC, ALT, AST, blood glucose, and insulin. Moreover, lauric acid significantly elevated the levels of SOD, GSH, catalase, and IL-10. Additionally, it lowered the hepatic levels of MDA, ROS, MPO, 4-HNE, interleukin (IL)-1β, and tumor necrosis factor (TNF-α). Furthermore, lauric acid significantly up-regulated the hepatic expression of IRS1, AMPK, PI3K, and SIRT1 genes. In parallel, lauric acid could improve the histopathological picture of the liver and reduce the liver apoptosis <i>via</i> decreasing the expression of annexin V (Anx V). Finally, our data proposed that lauric acid could be an effective candidate for the NAFLD treatment.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"454-467"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080933","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":"A QSAR study for predicting malformation in Zebrafish embryo","authors":"Mahsa Daneshmand, Jamileh SalarAmoli, Negin BaghbanZadeh","doi":"10.1080/15376516.2024.2338907","DOIUrl":"https://doi.org/10.1080/15376516.2024.2338907","url":null,"abstract":"BackgroundDevelopmental toxicity tests are extremely expensive, require a large number of animals, and are time-consuming. It is necessary to develop a new approach to simplify the analysis of deve...","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"95 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589696","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":"Investigation of the effects of Theranekron and Sorafenib treatments on carcinogenesis, apoptosis and biochemical profile in hepatocellular carcinoma in rats","authors":"Serdar Vanli, Firuze Kurtoglu, Beyza S. Alan, Gokhan Akcakavak, Ozgur Ozdemir","doi":"10.1080/15376516.2024.2332909","DOIUrl":"https://doi.org/10.1080/15376516.2024.2332909","url":null,"abstract":"This study aimed to investigate the effects of Tarantula cubensis alcohol extract (TCAE, Theranekron) and Sorafenib (S) treatments on carcinogenesis, apoptosis and biochemical profile of rats with ...","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"61 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590010","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":"Flow-through imaging and automated analysis of oil-exposed early stage Atlantic cod (Gadus morhua)","authors":"David R. Williamson, Emlyn J. Davies, Martin Ludvigsen, Bjørn Henrik Hansen","doi":"10.1080/15376516.2024.2338389","DOIUrl":"https://doi.org/10.1080/15376516.2024.2338389","url":null,"abstract":"Toxicology studies in early fish life stages serve an important function in measuring the impact of potentially harmful substances, such as crude oil, on marine life. Morphometric analysis of larva...","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"1 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589983","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":"Isoflurane pretreatment protects against myocardial ischemia/reperfusion injury via mediating lncRNA CASC15/miR-542-3p axis","authors":"Xiaoyi Wang, Yueping Wang, Yawei Yuan, Long Wang, Dawei Zhang","doi":"10.1080/15376516.2024.2327057","DOIUrl":"https://doi.org/10.1080/15376516.2024.2327057","url":null,"abstract":"The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, th...","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"8 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589981","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":"Does the accounting of the local symmetry fragments in quasi-SMILES improve the predictive potential of the QSAR models of toxicity towards tadpoles?","authors":"Alla P. Toropova, Andrey A. Toropov, Alessandra Roncaglioni, Emilio Benfenati","doi":"10.1080/15376516.2024.2332617","DOIUrl":"https://doi.org/10.1080/15376516.2024.2332617","url":null,"abstract":"Models of toxicity to tadpoles have been developed as single parameters based on special descriptors which are sums of correlation weights, molecular features, and experimental conditions. This inf...","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"33 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589987","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}