Toxicology Mechanisms and Methods最新文献_第4页

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 : 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 Nigella sativa 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":"https://doi.org/10.1080/15376516.2024.2399779","url":null,"abstract":"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 Nigella sativa (NS) against Cd-induced damage. Rats were assigned to: control, Cd-treated (0.5 mg/kg/d intraperitoneal [IP] injection), VC and Cd-treated (receiving 100 mg/kg/d VC orally and Cd concomitantly), NS and Cd-treated (receiving 20 mg/kg/d NS 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 NS caused significant reductions (p < 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 NS obviously reduced these degenerative changes and significantly improved pancreatic islet parameters and insulin immunoexpression. VC showed a better amendment than NS, but this difference was statistically insignificant. Therefore, VC and NS could be used as prophylactic agents that lessen Cd consequences on the pancreas.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2024-09-08","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

Correction. 更正。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-14 DOI: 10.1080/15376516.2024.2352924

引用次数: 0

Effects of benzoic acid synthesized from Cinnamomum cassia by green chemistry on valproic acid-induced neurotoxicity in zebrafish embryos. 用绿色化学方法从肉桂中合成的苯甲酸对丙戊酸诱导的斑马鱼胚胎神经毒性的影响

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-06-18 DOI: 10.1080/15376516.2024.2364899

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 Cinnamomum cassia 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":"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 Cinnamomum Cassia 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. eif4b, adsl, and shank3a 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.","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}

引用次数: 0

In-silico green toxicology approach toward discovering safer ligands for development of safe-by-design metal-organic frameworks. 为开发安全设计的金属有机框架发现更安全配体的硅学绿色毒理学方法。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-23 DOI: 10.1080/15376516.2024.2353364

Reyhane Khezri, Seyed Jamaleddin Shahtaheri, Elahe Khezri, Mahdi Niknam Shahrak, Monireh Khadem

{"title":"In-silico 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":"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. In-silico 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 LD50 and the probability of toxicological endpoints (cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, and ecotoxicity) were obtained and organized. According to retrieved LD50 data, the safest ligand was 5-hydroxyisophthalic. In contrast, the most hazardous ligand was 5-chlorobenzimidazole, with an LD50 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.","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}

引用次数: 0

Silver nanoparticle-induced cell damage via impaired mtROS-JNK/MnSOD signaling pathway. 银纳米粒子通过受损的 mtROS-JNK/MnSOD 信号通路诱导细胞损伤。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-13 DOI: 10.1080/15376516.2024.2350595

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":"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.","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}

引用次数: 0

Evaluating the possible genotoxicity of nanoaluminum incorporated in human vaccines and the potential protective role of nanocurcumin: an in vivo study. 评估人类疫苗中加入的纳米铝可能具有的遗传毒性以及纳米姜黄素的潜在保护作用：一项体内研究。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-22 DOI: 10.1080/15376516.2024.2352736

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 in vivo 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":"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.","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}

引用次数: 0

Assessment of TGx-DDI genes for genotoxicity in a comprehensive panel of chemicals. 评估综合化学品组中 TGx-DDI 基因的遗传毒性。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-04-15 DOI: 10.1080/15376516.2024.2335966

A Rasim Barutcu

{"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":"Background: 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.Methods: 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.Results: 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.Discussion: 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.","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}

引用次数: 0

Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats. 肥胖会加重双酚 A 对雌性大鼠神经炎症和神经退行性病变的影响。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-16 DOI: 10.1080/15376516.2024.2349538

Anuradha Mangla, Poonam Goswami, Bhaskar Sharma, Suramya Suramya, Garima Jindal, Mehjbeen Javed, Mohd Anas Saifi, Suhel Parvez, Tapas Chandra Nag, Sheikh Raisuddin

{"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":"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 via 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 (p < 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 (p < 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.","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}

引用次数: 0

Farnesoid X receptor modulator 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid represses liver fibrosis by inhibiting ERK/p38 signaling pathways. 类arnesoid X受体调节剂12β-（甲基苯甲酰基）-11,12-二氢齐墩果酸通过抑制ERK/p38信号通路抑制肝纤维化

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-14 DOI: 10.1080/15376516.2024.2349551

Yiming Li, Yunyang Bao, Simin Guo, Yang Li, Weishuo Fang, Na Zhang, Hongwei He

{"title":"Farnesoid X receptor modulator 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid represses liver fibrosis by inhibiting ERK/p38 signaling pathways.","authors":"Yiming Li, Yunyang Bao, Simin Guo, Yang Li, Weishuo Fang, Na Zhang, Hongwei He","doi":"10.1080/15376516.2024.2349551","DOIUrl":"10.1080/15376516.2024.2349551","url":null,"abstract":"Liver fibrosis is a common pathological process in the progression of several chronic liver diseases to cirrhosis and hepatocellular carcinoma. Therefore, the development of medications that can repress the progress of liver fibrosis is essential. We discovered that initially, 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid (12d-OA), a farnesoid X receptor (FXR) modulator, possessed potential anti-fibrotic properties. Through an in-depth study, we revealed that 12d-OA not only inhibited the expression of fibrogenic markers in the LX-2 cells and HSC-T6 cells but also exhibited significant protective effects against liver injury and liver fibrosis in bile duct ligation (BDL) rats. Further exploration of its molecular mechanism indicated that 12d-OA exerted antifibrotic activity by inhibiting the extracellular signal-regulated kinase (ERK)/stress-activated protein kinase (p38) signaling pathways. Consequently, the great effects of 12d-OA in vitro and in vivo suggest that it may be a good candidate for liver fibrosis.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"795-802"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863002","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

Insights into mitochondrial creatine kinase: examining preventive role of creatine supplement in doxorubicin-induced cardiotoxicity. 洞察线粒体肌酸激酶：研究肌酸补充剂在多柔比星诱发的心脏毒性中的预防作用。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-08-21 DOI: 10.1080/15376516.2024.2393825

Salaheddin M Sharif, David Hydock

{"title":"Insights into mitochondrial creatine kinase: examining preventive role of creatine supplement in doxorubicin-induced cardiotoxicity.","authors":"Salaheddin M Sharif, David Hydock","doi":"10.1080/15376516.2024.2393825","DOIUrl":"https://doi.org/10.1080/15376516.2024.2393825","url":null,"abstract":"Doxorubicin (Dox) is an effective and commonly used anticancer drug; however, it leads to several side effects including cardiotoxicity which contributes to poor quality of life for cancer patients. Creatine (Cr) is a promising intervention to alleviate Dox-induced cardiotoxicity. This study aimed to examine the effects of Cr beforeDox on cardiac mitochondrial creatine kinase (MtCK). Male rats were randomly assigned to one of two 4-week Cr feeding interventions (standard Cr diet or Cr loading diet) or a control diet (Con, n = 20). Rats in the standard Cr diet (Cr1, n = 20) were fed 2% Cr for 4-weeks. Rats in the Cr loading diet (Cr2, n = 20) were fed 4% Cr for 1-week followed by 2% Cr for 3-weeks. After 4-weeks, rats received either a bolus injection of 15 mg/kg Dox or a placebo saline injection (Sal). Five days post-injections left ventricle (LV) was excised and analyzed for MtCK expression using Western blot and ELISA. A significant drug effect was observed for LV mass (p < 0.05), post hoc testing revealed LV mass of Con + Dox and Cr2 + Dox was significantly lower than Con + Sal (p < 0.05). A significant drug effect was observed for MtCK (p = 0.03) through Western blot. A significant drug effect (p = 0.03) and interaction (p = 0.02) was observed for MtCK using ELISA. Post hoc testing revealed that Cr2 + Dox had significantly higher MtCK than Cr1 + Sal and Cr2 + Sal. Data suggest that a reduction in LV mass and MtCK may contribute to Dox-induced cardiotoxicity, and Cr supplementation may play a potential role in mitigating cardiotoxicity by preserving mitochondrial CK.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018704","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