Human & experimental toxicology最新文献

{"title":"Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats.","authors":"Salva Afshari, Mehdi Sarailoo, Vahid Asghariazar, Elham Safarzadeh, Masoomeh Dadkhah","doi":"10.1177/09603271241235408","DOIUrl":"10.1177/09603271241235408","url":null,"abstract":"<p><strong>Introduction: </strong>Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex.</p><p><strong>Materials and methods: </strong>Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels.</p><p><strong>Results: </strong>Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant.</p><p><strong>Conclusion: </strong>Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling thioacetamide-induced toxicity: Multi-organ damage and omitted bone toxicity.","authors":"Haodong Zhang, Jian Xu","doi":"10.1177/09603271241241807","DOIUrl":"10.1177/09603271241241807","url":null,"abstract":"<p><p>Thioacetamide (TAA), a widely employed hepatotoxic substance, has gained significant traction in the induction of liver failure disease models. Upon administration of TAA to experimental animals, the production of potent oxidative derivatives ensues, culminating in the activation of oxidative stress and subsequent infliction of severe damage upon multiple organs via dissemination through the bloodstream. This review summarized the various organ damages and corresponding mechanistic explanations observed in previous studies using TAA in toxicological animal experiments. The principal pathological consequences arising from TAA exposure encompass oxidative stress, inflammation, lipid peroxidation, fibrosis, apoptosis induction, DNA damage, and osteoclast formation. Recent in vivo and in vitro studies on TAA bone toxicity have confirmed that long-term high-dose use of TAA not only induces liver damage in experimental animals but also accompanies bone damage, which was neglected for a long time. By using TAA to model diseases in experimental animals and controlling TAA dosage, duration of use, and animal exposure environment, we can induce various organ injury models. It should be noted that TAA-induced injuries have a time-dependent effect. Finally, in our daily lives, especially for researchers, we should take precautions to minimize TAA exposure and reduce the probability of related organ injuries.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a nomogram for predicting mechanical ventilation need among acutely intoxicated patients with impaired consciousness.","authors":"Heba Ibrahim Lashin, Fatma Gaber Sobeeh, Zahraa Khalifa Sobh","doi":"10.1177/09603271241267214","DOIUrl":"https://doi.org/10.1177/09603271241267214","url":null,"abstract":"<p><strong>Background: </strong>A considerable portion of acutely intoxicated patients is presented with impaired consciousness. Early identification of those patients who require advanced medical care, such as mechanical ventilation (MV), can improve their prognosis.</p><p><strong>Methods: </strong>This study included 330 acutely intoxicated patients who were presented with impaired consciousness and admitted to Tanta University Poison Control Center, Egypt, in the period from January 2021 to December 2023. Patients were enrolled in derivation (257 patients) and validation (73 patients) cohorts. Patients' data were analyzed to develop and validate a predictive nomogram to determine the probability of MV need in acutely intoxicated patients.</p><p><strong>Results: </strong>Significant predictors for MV need were mean arterial blood pressure (OR = 0.96, <i>p</i> = .014), PaO₂ (OR = 0.96, <i>p</i> = .001), pH (OR = 0.00, <i>p</i> < . 001), and glucose/potassium ratio (OR = 1.59, <i>p</i> = .030). These four parameters were used to formulate a bedside nomogram. Receiver-operating characteristic (ROC) analysis for the proposed nomogram shows that area under the curve (AUC) = 95.7%, accuracy = 93.4%, sensitivity = 88.9%, and specificity = 95.1%. The internal validation for the developed nomogram was assessed using a bootstrapping method and calibration curve. Regarding external validation, AUCs for the developed nomogram probability was 96.5%, and for predicted probability using the developed nomogram was 97.8%.</p><p><strong>Conclusion: </strong>The current study provides a validated nomogram that could be used as a reliable tool for the accurate prediction of MV need among acutely intoxicated patients with impaired consciousness. It could assist in the early identification of patients who will require MV, especially in low-income countries with limited resources.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<b>Potential induction of</b> h<b>yperkeratosis in</b> r<b>ats'</b> c<b>ervi by gentamicin via induction of oxidative</b> s<b>tress,</b> i<b>nflammation and</b> a<b>poptosis</b>.","authors":"Walaa Yehia Abdelzaher, Mina Ezzat Attya, Mohamed Ahmed Zeen El-Din, Alaa Gamal El Satae, Hatem A Mohamed, Remon R Rofaeil","doi":"10.1177/09603271231225744","DOIUrl":"10.1177/09603271231225744","url":null,"abstract":"<p><p>The present study aimed to identify the possible effect of gentamicin (GEN) in Rats' Cervi. Estradiol Valerate (EV) was used to induce cervical hyperkeratosis. GEN was administered in absence of EV. Serum and cervical GEN concentration were determined. Levels of malondialdehyde (MDA), total nitrites/nitrate (NOx), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), sirtuin type 1 (Sirt1) and nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2) were measured in cervix tissue. Expression of BAX and Bcl2 were determined. Cervical histopathological examination was done. EV and GEN significantly increased MDA, NOx, TNF-α and BAX/Bcl2 ratio with decrease in GSH, Nrf2 and Sirt1 levels in cervical tissue. Histopathological picture of diffuse and marked hyperkeratosis was detected in EV and GEN groups. In conclusion, GEN-induced cervical hyperkeratosis via induction of oxidative stress, inflammation and apoptosis.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139081180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram for predicting mechanical ventilation need among acutely intoxicated patients with impaired consciousness: Correspondence.","authors":"Hineptch Daungsupawong, Viroj Wiwanitkit","doi":"10.1177/09603271241285992","DOIUrl":"https://doi.org/10.1177/09603271241285992","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic P53 upregulation and the genotoxic potential of acesulfame-K treatment in rats with a special emphasis on in vitro lymphocyte and macrophage activity testing.","authors":"Faten F Mohammed, Eman G Abdelrazik, Abeer Anwar, Sherein S Abdelgayed","doi":"10.1177/09603271241236900","DOIUrl":"10.1177/09603271241236900","url":null,"abstract":"<p><p>Acesulfame-k (Ace-k) is a widely used artificial sweetener in various products, and long-term cumulative and multisource exposure is possible despite inadequate toxicological data confirming its safety. Ninety male rats were divided into two main groups according to their body weight into immature and mature rats. Each group was subdivided into 3 subgroups: control untreated, 30 and 90 mg/kg b. w of Ace-k via gastric intubation. The treatment was performed daily 5 days per week for 12 weeks. At the end of the experimental period, blood samples were collected for in vitro testing of lymphocyte proliferation rate, comet assay, and macrophage activity about nitric oxide (NO) production. In addition, the collection of liver specimens was performed for P53 gene expression and histopathological evaluation. The results revealed that Ace-k induced modulation in lymphocyte proliferation rate and affected the production of NO by macrophages while increasing in tail moment in a dose-dependent manner that varied among different age groups. The upregulation of P53 in the liver was correlated with increased polyploidization and necro apoptotic reaction and various histopathological hepatic alterations. The present data revealed that chronic treatment of rats with Ace-k affects lymphocyte proliferation and macrophage activity in a dose-dependent manner. In addition, the genotoxic and hepatotoxic potential of Ace-k were confirmed.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for glioblastoma are shared by other brain tumor types.","authors":"Carr J Smith, Thomas A Perfetti, Chirayu Chokshi, Chitra Venugopal, J Wesson Ashford, Sheila K Singh","doi":"10.1177/09603271241241796","DOIUrl":"10.1177/09603271241241796","url":null,"abstract":"<p><p>The reported risk factors for glioblastoma (GBM), i.e., ionizing radiation, Li-Fraumeni syndrome, Neurofibromatosis I, and Turcot syndrome, also increase the risk of other brain tumor types. Risk factors for human GBM are associated with different oncogenic mutation profiles. Pedigreed domestic dogs with a shorter nose and flatter face (brachycephalic dogs) display relatively high rates of glioma formation. The genetic profiles of canine gliomas are also idiosyncratic. The association of putatively different mutational patterns in humans and canines with GBM suggests that different oncogenic pathways can result in GBM formation. Strong epidemiological evidence for an association between exposure to chemical carcinogens and an increased risk for development of GBM is currently lacking. Ionizing radiation induces point mutations, frameshift mutations, double-strand breaks, and chromosomal insertions or deletions. Mutational profiles associated with chemical exposures overlap with the broad mutational patterns seen with ionizing radiation. Weak statistical associations between chemical exposures and GBM reported in epidemiology studies are biologically plausible. Molecular approaches comparing reproducible patterns seen in spontaneous GBM with analogous patterns found in GBMs resected from patients with known significant exposures to potentially carcinogenic chemicals can address difficulties presented by traditional exposure assessment.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milestone for hormesis and human and experimental toxicology.","authors":"A Wallace Hayes, Kai Savolainen","doi":"10.1177/09603271241236274","DOIUrl":"10.1177/09603271241236274","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the effectiveness of fresh frozen plasma transfusion as adjuvant treatment in acute organophosphate-poisoned patients: A randomized clinical trial.","authors":"Somaia Abdelhamid, Manal Abel Kareem, Soha Ashry, Sara Saeed","doi":"10.1177/09603271241260655","DOIUrl":"10.1177/09603271241260655","url":null,"abstract":"<p><p>Organophosphorus (OP) poisoning is a significant cause of morbidity and mortality worldwide. Recent research has explored new approaches to improving treatment options, which present several challenges. This study aimed to evaluate the role of fresh frozen plasma (FFP) as an adjunctive therapy for acute OP intoxication. A prospective single-blinded randomized clinical trial was conducted on patients of both sexes admitted to the Intensive Care Unit (ICU) of the Poison Control Center at Ain Shams University Hospital (PCC-ASUH) with acute OP toxicity during the period from the beginning of August 2022 to the end of July 2023. According to the Peradeniya score, Group I consisted of 48 patients (52%) with moderate OP poisoning, and Group II consisted of 44 patients (48%) with severe OP poisoning. Patients in the moderate group were assigned to receive either standard treatment (Group Ia, <i>n</i> = 24) or standard treatment plus FFP (Group Ib, <i>n</i> = 24). In addition, patients in the severe group were assigned to receive either standard treatment (Group IIa, <i>n</i> = 22) or standard treatment plus FFP (Group IIb, <i>n</i> = 22). A total of 46 patients received FFP transfusion. The authors demonstrated that the early use of a total of nine packs of FFP (250 mL each) over three consecutive days significantly reduced the total doses of atropine and oximes, the total hospitalization period, and the requirement for mechanical ventilation in patients with OP poisoning, both in the moderate and severe groups.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In silico</i> evaluations of phytochemicals from <i>Withania somnifera</i> exhibiting anticancer activity against NAD[P]H-quinone oxidoreductase.","authors":"Sushma Jahagirdar, Harshini Praveen Kumar, Smitha S Bhat, Arpita Poddar, Pratim Kumar Chattaraj, Sheikh F Ahmad, Shashanka K Prasad","doi":"10.1177/09603271241291399","DOIUrl":"https://doi.org/10.1177/09603271241291399","url":null,"abstract":"<p><strong>Background: </strong>Cancer is a leading cause of death globally and in the US, prompting research into medicinal plants with anticancer properties. <i>Withania somnifera</i>, or Ashwagandha, is one such plants, known for its diverse pharmacological effects. Withaferin A and Viscosalactone B are two compounds found in Ashwagandha with known anticancer activity. The protein NQO1, overexpressed in various cancers, was the focus of this study.</p><p><strong>Hypothesis and aim: </strong>We hypothesize that specific phytochemicals in <i>Withania somnifera</i> can effectively interact with and inhibit the NQO1 protein, thereby exhibiting anticancer properties. This study aims to identify these interactions using in silico approaches.</p><p><strong>Methodology: </strong>CFDT was performed using the Gaussian 16 program package, followed by QSAR analysis of the compounds in the PASS online web server. The Schrodinger suite was used to carry out ligand and protein preparation, molecular docking, and molecular dynamic simulation to analyse the interaction of these compounds with NQO1 and ADME studies. Protox-II and SWISSADME tools were used to predict the toxicity and blood-brain barrier permeability of the phytochemicals.</p><p><strong>Results and conclusion: </strong>CDFT and frontier molecular orbital analyses predicted the stability and reactivity of all the selected molecules. QSAR analysis predicted the biological activity and toxicity of the compounds. Withaferin A exhibited the highest glide gscore (-4.953 kcal/mol) and demonstrated 6 hydrogen bond interactions with NQO1, suggesting its potential as an anticancer agent. Conceptual density functional theory-based analysis suggested the strong electrophilicity of the ligands, further supporting their potential anticancer activities. Viscosalactone B, another phytochemical from Ashwagandha, also showed interactions involving 6 hydrogen bonds with NQO1, with a glide gscore of (-4.593 kcal/mol). Molecular dynamic simulations validated the stability of the Withaferin A-NQO1 complex. ADME-T properties predicted high oral absorption for the selected ligands, indicating that Withaferin A could be a viable orally administered drug.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}