Toxicology Mechanisms and Methods最新文献

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Cadmium-induced pancreatic toxicity in rats: comparing vitamin C and Nigella sativa as protective agents: a histomorphometric and ultrastructural study. 镉诱导的大鼠胰腺毒性:比较维生素 C 和黑麦草的保护作用:组织形态计量学和超微结构研究。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-02-01 Epub Date: 2024-09-08 DOI: 10.1080/15376516.2024.2399779
Asmaa F A Dawood, Hanan M Alharbi, Faten I Ismaeel, Shahina M Khan, Hanan D Yassa, Nermeen N Welson, Fatma El-Zahraa A Abd El-Aziz
{"title":"Cadmium-induced pancreatic toxicity in rats: comparing vitamin C and <i>Nigella sativa</i> as protective agents: a histomorphometric and ultrastructural study.","authors":"Asmaa F A Dawood, Hanan M Alharbi, Faten I Ismaeel, Shahina M Khan, Hanan D Yassa, Nermeen N Welson, Fatma El-Zahraa A Abd El-Aziz","doi":"10.1080/15376516.2024.2399779","DOIUrl":"10.1080/15376516.2024.2399779","url":null,"abstract":"<p><p>The study aimed to assess the toxic effect of cadmium (Cd) on the exocrine and endocrine functions of pancreas, the changes in pancreatic tissue after Cd withdrawal, and the protective effects of vitamin C (VC) and <i>Nigella sativa</i> (<i>NS</i>) against Cd-induced damage. Rats were assigned to: control, Cd-treated (0.5<b> </b>mg/kg/d intraperitoneal [IP] injection), VC and Cd-treated (receiving 100 mg/kg/d VC orally and Cd concomitantly), <i>NS</i> and Cd-treated (receiving 20 mg/kg/d <i>NS</i> and Cd, simultaneously), and Cd withdrawal (receiving Cd for 30 d then living free for recovery for other 30 d). Blood samples were collected and post-sacrifice pancreatic specimens were processed for light and electron microscope study. Quantitative analyses of pancreatic collagen area%, pancreatic islet parameters, β cell density, and insulin immunoexpression were done. Fasting blood glucose was significantly increased in Cd-treated and Cd-withdrawal groups, while co-treatment with VC and <i>NS</i> caused significant reductions (<i>p</i> < 0.05). Cd-induced extensive degenerative changes in pancreatic acini and islets at light and ultrastructure levels. Obvious fibrosis and congestion of blood vessels were noticed. Significant reductions in pancreatic islet number, volume, and surface area and diminished beta cell count and insulin immunoexpression were observed. After withdrawal of Cd, the whole pancreatic tissue still showed a serious impact. Concomitant treatment with VC or <i>NS</i> obviously reduced these degenerative changes and significantly improved pancreatic islet parameters and insulin immunoexpression. VC showed a better amendment than <i>NS</i>, but this difference was statistically insignificant. Therefore, VC and <i>NS</i> could be used as prophylactic agents that lessen Cd consequences on the pancreas.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"181-196"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142155033","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}
引用次数: 0
Simultaneous measurement of fentanyl, fentanyl analogues and other drugs of abuse by multiplex bead assay.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-30 DOI: 10.1080/15376516.2025.2457336
J P Smith, M Alexander-Scott, C Striley, D Sammons
{"title":"Simultaneous measurement of fentanyl, fentanyl analogues and other drugs of abuse by multiplex bead assay.","authors":"J P Smith, M Alexander-Scott, C Striley, D Sammons","doi":"10.1080/15376516.2025.2457336","DOIUrl":"https://doi.org/10.1080/15376516.2025.2457336","url":null,"abstract":"<p><p>Quantification of illicit drugs and controlled substances, in urine or as surface contamination, is often performed using expensive analytical techniques such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). A time and cost-effective semi-quantitative surface-wipe and urine screening multiplex immunoassay for fentanyl and its analogues was developed in this investigation. We previously created a surface wipe multiplex immunoassay for methamphetamine, caffeine, cocaine, tetrahy-drocannabinol (THC) and oxycodone. This fluorescent covalent microsphere immunosorbent assay (FCMIA) is a competitive assay where drugs compete with protein-drug conjugates attached to microspheres for antibodies. It was assembled using a commercially available fentanyl antibody and protein-conjugate. Surface recovery from ceramic tiles was assessed by FCMIA, with results ranging from 26% for fentanyl to 60% for methamphetamine. Only fentanyl and its structurally similar analogues showed significant response to the fentanyl assay whereas, analogues structurally similar to carfentanil gave no response. Non-fentanyl drug assays did not appreciably detect fentanyl or its analogues. Overall, this method is a useful tool for assessing surface contamination and the effectiveness of decontamination by multiple drugs of abuse, potentially lowering workplace exposures. To broaden applicability, different antibodies or aptamers must be developed to detect structural differences found in classes of analogues such as carfentanil.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068281","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}
引用次数: 0
Mechanisms involved in the valproic acid-induced hepatotoxicity: A Comprehensive review.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-27 DOI: 10.1080/15376516.2025.2459176
Rohan Kadam, Mahesh Palkar, Ravindra Babu Pingili
{"title":"Mechanisms involved in the valproic acid-induced hepatotoxicity: A Comprehensive review.","authors":"Rohan Kadam, Mahesh Palkar, Ravindra Babu Pingili","doi":"10.1080/15376516.2025.2459176","DOIUrl":"https://doi.org/10.1080/15376516.2025.2459176","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Adverse drug reactions (ADR) remain a challenge in modern healthcare, particularly given the increasing complexity of therapeutics. WHO's definition of an adverse drug reaction as a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function. This definition underscores the importance of monitoring and mitigating unintended drug effects, particularly for widely used medications like valproic acid (VPA). An anticonvulsant medicine which is frequently used in treatment of epilepsy and other neurological conditions is valproic acid (VPA), is frequently associated with hepatotoxicity, a severe ADR that complicates its clinical use, which can take two different forms: Type I, which is defined by dose-dependent and reversible liver damage, and Type II, an idiosyncratic reaction that can result in severe liver failure, frequently complicates its clinical application. Oxidative stress, the creation of reactive metabolites, mitochondrial dysfunction, carnitine shortage, immune-mediated reactions, glutathione depletion, and blockage of the bile salt export pump (BSEP) are some of the numerous underlying mechanisms of Valproic acid-induced hepatic damage. The production of reactive oxygen species and the liver's antioxidant protection are out of balance as a cause of oxidative stress, which is a significant factor in VPA intoxication. Reactive oxygen species (ROS) are defined as \"a collective term for a variety of reactive molecules and free radicals derived from molecular oxygen\". This includes species such as superoxide anion, hydrogen peroxide, hydroxyl radical, and singlet oxygen, have long been implicated in oxidative damage inflicted on fatty acids, DNA and proteins as well as other cellular components. The integrity of the hepatocyte may be compromised by the over production of ROS, which can create cellular damage such as protein oxidation and lipid peroxidation. Liver damage is further exacerbated by reactive metabolites produced by VPA metabolism, which have the ability to covalently attach to biological macromolecules. As VPA reduces mitochondrial bioenergetics, it causes ATP depletion and consequent cellular death, which is another important component of VPA-induced hepatotoxicity. Increased urea cycle activity leads to hyperammonemia, which aggravates the liver and causes neurotoxicity. VPA can also accelerate the build-up of fatty acids, which increases the risk of steatosis, due to its interaction with the metabolism of carnitine. Immune-mediated processes have been shown to increase liver injury, implying that the immunity system may possibly be involved in VPA hepatotoxicity. Hepatocyte injury and cholestasis are caused by BSEP inhibition, which impairs bile flow. As another point of view, glutathione depletion, a result of oxidative stress, reduces the liver's ability to neutralize toxic compounds. The co","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-30"},"PeriodicalIF":3.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053779","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}
引用次数: 0
Sentinel role of military dogs in detecting genotoxic agents in the environment during military operations: a pilot study. 军事行动中军犬在环境中检测基因毒性物质中的哨兵作用:一项试点研究。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-26 DOI: 10.1080/15376516.2025.2453731
Lorenzo Tidu, Stefano Ciccarelli, Stefania De Sanctis, Florigio Lista, Rosaria Ferreri, Elisa Regalbuto, Fabio Grizzi, Gianluigi Taverna, Alessandro Poli, Marco Bruzzone, Marcello Ceppi, Paola Roggieri, Claudia Bolognesi
{"title":"Sentinel role of military dogs in detecting genotoxic agents in the environment during military operations: a pilot study.","authors":"Lorenzo Tidu, Stefano Ciccarelli, Stefania De Sanctis, Florigio Lista, Rosaria Ferreri, Elisa Regalbuto, Fabio Grizzi, Gianluigi Taverna, Alessandro Poli, Marco Bruzzone, Marcello Ceppi, Paola Roggieri, Claudia Bolognesi","doi":"10.1080/15376516.2025.2453731","DOIUrl":"10.1080/15376516.2025.2453731","url":null,"abstract":"<p><p>During out-of-area military operations, the presence of carcinogenic and/or genotoxic agents has been reported, posing potential health risks to deployed soldiers. Military working dogs (MWDs), trained to detect explosives in the same environments as soldiers, could also serve as sentinel animals, providing valuable information on exposure to hazardous agents. These dogs can help identify environmental and potential adverse effects on their health and that of their handlers, possibly before relevant pathologies manifest. This study aims to evaluate the effectiveness of 33 Italian Army MWDs, deployed to the Lebanese theater for six consecutive months from October 2013 to January 2015, as sentinel animals for detecting exposure to genotoxic agents. The Cytokinesis-Block MicroNucleus (CBMN) assay was used to assess DNA damage, cytostasis, and cytotoxicity in the lymphocytes of these dogs. DNA damage events were specifically scored in once-divided binucleated cells (BCs) and included: a) micronuclei (MNi), indicative of chromosome breakage and/or whole chromosome loss; b) nucleoplasmic bridges (NPBs), a marker of DNA misrepair and/or telomere end-fusions; and c) nuclear buds (NBUDs), which signal the elimination of amplified DNA and/or DNA repair complexes. Our findings revealed an increase in chromosomal damage, assessed before and after deployment, with a statistically significant rise in MNi frequency, thus supporting the use of MWDs as sentinels for human exposure to hazardous agents.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012055","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}
引用次数: 0
Clinical and Safety Outcomes Associated with Aristolochic Acid Exposure: A Systematic Review and Meta-analysis.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-22 DOI: 10.1080/15376516.2025.2457340
Ting Cui, Shumei Che, Xingxu Yan, Rongrong Yang, Zhenna Xu, Sijia Liu, Ying Li, Chenyu Hao, Junhan Jiang, Lili Song, Hua Jin, Yubo Li
{"title":"Clinical and Safety Outcomes Associated with Aristolochic Acid Exposure: A Systematic Review and Meta-analysis.","authors":"Ting Cui, Shumei Che, Xingxu Yan, Rongrong Yang, Zhenna Xu, Sijia Liu, Ying Li, Chenyu Hao, Junhan Jiang, Lili Song, Hua Jin, Yubo Li","doi":"10.1080/15376516.2025.2457340","DOIUrl":"https://doi.org/10.1080/15376516.2025.2457340","url":null,"abstract":"<p><p>Current studies have clearly shown that aristolochic acid (AA) exposure can induce a variety of diseases, such as kidney disease, liver cancer, and urinary tract cancer (UTC). However, no studies have systematically analyzed and integrated these results. Therefore, we aimed to elucidate the association between AA exposure and the risk of safety outcomes for AA-related overall disease and different types of disease it causes. We conducted an exhaustive search of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant material up to April 2024. For AA-related overall disease, AA exposure was significantly associated with an increased incidence of AA-related overall disease (OR: 1.289, 95% CI: 1.183 - 1.404). For different types of disease, AA exposure was significantly associated with increased incidence of kidney disease (OR: 1.279, 95% CI: 1.029 - 1.590), UTC (OR: 1.842, 95% CI: 1.376 - 2.465) and liver cancer (OR: 1.146, 95% CI: 1.040 - 1.262). No significant association was found between AA exposure and the incidence of brain disease (OR: 1.161, 95% CI: 0.989 - 1.362). This study systematically analyzed various safety outcomes associated with AA exposure to provide a solid scientific basis for future prevention strategies and clinical management.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024807","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}
引用次数: 0
Correction.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-22 DOI: 10.1080/15376516.2025.2454760
{"title":"Correction.","authors":"","doi":"10.1080/15376516.2025.2454760","DOIUrl":"https://doi.org/10.1080/15376516.2025.2454760","url":null,"abstract":"","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1"},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024824","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}
引用次数: 0
"Brij 35 inhibited the CYP2E1-mediated metabolism and P-gp mediated transport of Paracetamol in rats and in vitro models: Amelioration of Paracetamol Toxicity. Brij 35在大鼠和体外模型中抑制cyp2e1介导的代谢和P-gp介导的对乙酰氨基酚转运:改善对乙酰氨基酚的毒性。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-21 DOI: 10.1080/15376516.2025.2457331
Nagabhushanam Chunduru, Ravindra Babu Pingili, Vijaya R Dirisala, K, Prasad
{"title":"\"Brij 35 inhibited the CYP2E1-mediated metabolism and P-gp mediated transport of Paracetamol in rats and <i>in vitro</i> models: Amelioration of Paracetamol Toxicity.","authors":"Nagabhushanam Chunduru, Ravindra Babu Pingili, Vijaya R Dirisala, K, Prasad","doi":"10.1080/15376516.2025.2457331","DOIUrl":"https://doi.org/10.1080/15376516.2025.2457331","url":null,"abstract":"<p><p>The harmful by-product of paracetamol is known as N-Acetyl-p-benzoquinoneimine, (NAPQI). When paracetamol is given at therapeutic dosages or in excess, it undergoes Phase I metabolism in the liver via Cytochrome P-450 2E1 (CYP2E1), and then it produces NAPQI. Previous studies reported that a non-ionic surfactant known as Brij 35 (Polyoxyethylene lauryl ether) has been shown to be an effective inhibitor of CYP2E1 and P-glycoprotein (P-gp). Hence, this <i>in vitro</i> and <i>in vivo</i> investigation set out to assess Brij 35 impact on paracetamol CYP2E1-mediated metabolism. For the <i>in vitro</i> investigation, isolated rat hepatocytes were used. Male Wistar rats were used for <i>in vivo</i> studies. There were thirty rats in total, with six individuals each group distributed among the five groups. The first group animals received 0.5% sodium carboxy methyl cellulose (control group); the second group animals treated with 300 mg/kg of paracetamol; the third group animals treated with Brij 35 (5 mg/kg) along with 300 mg/kg of paracetamol; the fourth group animals treated with 10 mg/kg of Brij 35 along with 300 mg/kg of paracetamol and the fifth group animals treated with 20 mg/kg of Brij 35 along with 300 mg/kg of paracetamol for consecutive 21 days. The current study found that paracetamol plasma concentrations were much higher and NAPQI plasma concentrations were much lower when Brij 35 was co-administered may be due to inhibition of CYP2E1-mediated metabolism and P-gp-mediated intestinal transport of paracetamol. Brij 35 also reduced the increased hepatic and renal markers with significant hepatoprotective and nephroprotective changes in the histopathological investigation.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012090","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}
引用次数: 0
Disruptive multiple cell death pathways of bisphenol-A. 双酚a的破坏性多细胞死亡途径。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-15 DOI: 10.1080/15376516.2024.2449423
Yukta S, Milan K L, Kannan Harithpriya, Cai Zong, S Sahabudeen, Gaku Ichihara, K M Ramkumar
{"title":"Disruptive multiple cell death pathways of bisphenol-A.","authors":"Yukta S, Milan K L, Kannan Harithpriya, Cai Zong, S Sahabudeen, Gaku Ichihara, K M Ramkumar","doi":"10.1080/15376516.2024.2449423","DOIUrl":"https://doi.org/10.1080/15376516.2024.2449423","url":null,"abstract":"<p><p>Endocrine-disrupting chemicals (EDCs) significantly contribute to health issues by interfering with hormonal functions. Bisphenol A (BPA), a prominent EDC, is extensively utilized as a monomer and plasticizer in producing polycarbonate plastic and epoxy resins, making it one of the highest-demanded chemicals in commercial use. This is the major component used in plastic products, including bottles, containers, storage items, and food serving ware. Exposure of BPA happens through oral, respiratory, transdermal routes and eye contact. As an EDC, BPA disrupts hormonal binding, leading to various health problems, such as cancers, reproductive abnormalities, metabolic syndrome, immune dysfunction, neurological effects, cardiovascular problems, respiratory issues, and obesity. BPA mimics the hormone estrogen but exhibits a weak affinity for estrogen receptors. This weak binding affinity triggers multiple cell death pathways, including necroptosis, pyroptosis, apoptosis, ferroptosis, and autophagy, across different cell types. Numerous clinical, <i>in-vitro</i>, and <i>in-vivo</i> experiments have demonstrated that BPA exposure results in unfavorable health effects. This review highlights the mechanisms of cell death pathways initiated through BPA exposure and the associated negative health consequences. The extensive use of BPA and its frequent detection in environmental and biological models underscore the urgent need for further investigation into its effects and the development of safe alternatives. Addressing the health risks posed by BPA involves a comprehensive approach that includes reducing exposure and finding novel substitutes to lessen its detrimental impact on humans.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012051","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}
引用次数: 0
HepG2 spheroids cultured in alginate microcapsules as a model for exploring mitochondrial and glycolytic metabolism using the Seahorse XFe24 Analyzer. 海藻酸盐微胶囊中培养的HepG2球体作为模型,使用Seahorse XFe24分析仪探索线粒体和糖酵解代谢。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-06 DOI: 10.1080/15376516.2024.2447740
Raul Ghiraldelli Miranda, Ivo F Machado, Anabela Pinto Rolo, Daniel Junqueira Dorta, Carlos Manuel Marques Palmeira
{"title":"HepG2 spheroids cultured in alginate microcapsules as a model for exploring mitochondrial and glycolytic metabolism using the Seahorse XFe24 Analyzer.","authors":"Raul Ghiraldelli Miranda, Ivo F Machado, Anabela Pinto Rolo, Daniel Junqueira Dorta, Carlos Manuel Marques Palmeira","doi":"10.1080/15376516.2024.2447740","DOIUrl":"https://doi.org/10.1080/15376516.2024.2447740","url":null,"abstract":"<p><p>Mitochondria are affected by chemical substances and play a critical role in drug-induced liver injury (DILI). Chemical substances can have a significant impact on various cellular processes, such as the disruption of oxidative phosphorylation, oxidative stress, and alteration of glucose metabolism. Given the consequences of these effects, it is crucial to understand the molecular pathways of chemical substances in the context of hepatotoxicity to prevent and treat DILI. In this regard, the Seahorse XFe24 Analyzer is a valuable tool for assessing mitochondrial bioenergetics and glucose metabolism. The Mito Stress Test and Glycolytic Rate Assay allow real-time assessment of the metabolic state after chemical exposure. Additionally, HepG2 spheroids have emerged as an important alternative tool for assessing hepatotoxicity, as they provide results that are more comparable to those found in humans than monolayer cultures or animal tests (such as rodent tests). By integrating these two powerful tools, it is possible to bridge the gap between animal and human tests, resulting in more reliable results in the assessment of human hepatotoxicity and DILI. However, because of the high variability in characteristics between 3D cultures (such as spheroids and organoids), XF analyzer assays are not well optimized for use with HepG2 spheroids. Here, we describe a streamlined and optimized protocol for performing the Mito Stress Test and Glycolytic Rate Assay using HepG2 spheroids cultured in alginate microcapsules in the Seahorse XFe24 Analyzer.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932687","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}
引用次数: 0
Pymetrozine induced remarkable hemato-biochemical modifications and genotoxicity in vital organs of bighead carp (Aristichthys nobilis). 吡蚜酮对鳙鱼重要器官产生了显著的血液生化改变和遗传毒性。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-01-06 DOI: 10.1080/15376516.2024.2440738
Munir Ahmad, Yasir Mahmood, Abdul Ghaffar, Riaz Hussain, Shazia Anjum, Dalia Fouad, Farid Shokry Ataya, Ahrar Khan
{"title":"Pymetrozine induced remarkable hemato-biochemical modifications and genotoxicity in vital organs of bighead carp (<i>Aristichthys nobilis</i>).","authors":"Munir Ahmad, Yasir Mahmood, Abdul Ghaffar, Riaz Hussain, Shazia Anjum, Dalia Fouad, Farid Shokry Ataya, Ahrar Khan","doi":"10.1080/15376516.2024.2440738","DOIUrl":"10.1080/15376516.2024.2440738","url":null,"abstract":"<p><p>Pymetrozine (a pyridine azomethine pesticide) is one of the most commonly and frequently used insecticides. Scanty information is available about the deleterious effects of Pymetrozine on fish especially bighead carp. Hence, the current study investigated chronic toxicological effects of pymetrozine in bighead carp. A total of 80 fish were reared and divided into four groups(A-D) each containing 20 fish. Pymetrozine was given to experimental fish of groups B, C, and D mixed in water at doses of 5, 10, and 15 mg/L respectively for 30 days. Group A remained as control group. On days 10, 20, and 30 of the experiment, blood and other visceral tissues were collected for analysis of genotoxic effects, erythrocytic morphological and nuclear changes, antioxidant enzymes, and oxidative stress profile. The results revealed significantly higher values of various nuclear abnormalities (erythrocyte with micronuclei, red blood cells with condensed and lobed nuclei) and morphological changes (pear shaped erythrocyte, spindle shaped erythrocytes and spherocyte) in erythrocytes of bighead carp. The investigations on status of antioxidant enzymes and oxidative stress indicated higher values of oxidative stress biomarkers and lower values of antioxidant enzymes in visceral organs (brain, liver, gills, and kidneys) of treated fish. The findings on genotoxic potential of pymetrozine revealed a considerably increased frequency of DNA damage in isolated cells of multiple tissues (brain, liver, gills, and kidneys) of experimental fish at higher doses. In conclusion, it may be suggested that pymetrozine induces toxic effects via disruption of physiological mechanisms of multiple visceral organs of bighead carp.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932691","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}
引用次数: 0
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