Toxicology Reports最新文献

{"title":"Safety evaluation of <i>Akkermansia massiliensis</i> sp. nov. DSM 33459.","authors":"Jeffrey Pitt, Mark R Bauter, Ritesh Kumar, Oliver Hasselwander, Ashley A Hibberd, Helene Kane, Qiong Wang, Isabelle Auzanneau, Stéphanie Bry, Elisabeth David, Pauline Seguinot, Frank Burns, Amy B Smith","doi":"10.1016/j.toxrep.2025.102042","DOIUrl":"10.1016/j.toxrep.2025.102042","url":null,"abstract":"<p><p>A novel strain of <i>Akkermansia massiliensis</i> sp. nov., designated as DSM 33459, was isolated from the feces of a healthy human donor. In order to fully assess the safety of this strain, following previously performed full genomic assessment, further <i>in-vitro</i> characterization and a combined <i>in-vivo</i> subchronic 28-day and 90-day toxicity study is reported herein. <i>A. massiliensis</i> DSM 33459 is tolerant to bile, somewhat tolerant to gastric juice pH conditions, and does not exhibit any aspects of virulence. This strain also demonstrates the ability to engraft the gastrointestinal tract of rats, persisting with continuous administration of the strain until the end of the study. Exposure to 2000 mg/kg BW/day <i>A. massiliensis</i> DSM 33459 did not produce any evidence of toxicity after either 28- or 90-days of exposure and did not translocate across the gastrointestinal barrier. Therefore, the NOEL for <i>A. massiliensis</i> DSM 33459, administered for 28- or 90-days, was determined to be the limit dose at 2000 mg/kg/day in male and female rats, a level which meets or exceeds calculated dose equivalent of 5.62 × 10¹¹ CFU/kg/day.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102042"},"PeriodicalIF":0.0,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing precision medicine: Uncovering biomarkers and strategies to mitigate immune-related adverse events in immune checkpoint inhibitors therapy.","authors":"K L Nityashree, P Rachitha, Shilpa Hanchinmane, Vinay B Raghavendra","doi":"10.1016/j.toxrep.2025.102035","DOIUrl":"10.1016/j.toxrep.2025.102035","url":null,"abstract":"<p><p>Immune-related adverse events (irAEs) can have a major influence on patient outcomes, but their usage is frequently confounded by immune checkpoint inhibitors (ICIs), which have revolutionized cancer treatment by increasing anti-tumor immunity. With a focus on immunological dysregulation and the resulting tissue-specific toxicities, this review clarifies the fundamental processes of irAEs. We look at contemporary clinical treatment techniques to lessen the impact of these adverse events, such as the application of immunosuppressants and patient monitoring procedures. Additionally, it is emphasized how future research is necessary to find predictive biomarkers that can forecast the development of irAEs, allowing for early intervention and individualized therapy methods. In order to improve the therapeutic index of ICIs, we also examine the crucial balance between optimizing anti-tumor activity and reducing immunotoxicity. This study aims to further the existing discussion on enhancing the safety and effectiveness of ICI medicines, which will eventually improve cancer patient care, by pointing out possible research avenues.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102035"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-related adverse events in immunotherapy: Challenges in diagnosis, monitoring, and management.","authors":"Mohd Aftab Siddiqui, Afreen Usmani, Mohd Nazam Ansari, Rania I M Almoselhy","doi":"10.1016/j.toxrep.2025.102036","DOIUrl":"10.1016/j.toxrep.2025.102036","url":null,"abstract":"<p><p>This article provides a comprehensive overview of safety and monitoring guidelines in immunotherapy, a rapidly advancing field in cancer and autoimmune treatment. Immunotherapy, which harnesses the body's immune system to combat diseases, has shown remarkable promise but presents unique safety challenges requiring rigorous oversight. The article examines various immunotherapies, including immune checkpoint inhibitors, monoclonal antibodies, and cytokine therapies, highlighting potential adverse effects and the critical need for careful monitoring. It emphasizes pre-treatment assessments, risk stratification, and genetic and biomarker screening to identify high-risk patients. Detailed monitoring protocols, including laboratory tests, imaging, and clinical evaluations, are discussed to detect immune-related adverse events (irAEs) early. Strategies for managing both acute and chronic toxicities, such as dose adjustments and treatment interruptions, are outlined to ensure timely intervention and individualized care. The article also underscores the importance of patient education, compliance, and supportive care, emphasizing a multidisciplinary approach. Through this detailed review, healthcare professionals gain practical guidelines to optimize the safe and effective use of immunotherapies in clinical settings.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102036"},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-silico</i> novel thioredoxin-interacting protein inhibitors from <i>Syzygium aromaticum</i> and <i>Terminalia chebula</i> and their validations to combat arsenic-Induced toxicity in Vero cells.","authors":"Manoj Soni, Yangala Sudheer Babu, Vivek Kumar, Bharat Singh, Mettle Brahma, Mulaka Maruthi, Ajit Kumar, Vijay Kumar","doi":"10.1016/j.toxrep.2025.102027","DOIUrl":"10.1016/j.toxrep.2025.102027","url":null,"abstract":"<p><p>Arsenic is a toxic metalloid that can lead to oxidative stress in cells by inducing reactive oxygen species (ROS) and interfering with cellular antioxidant defenses. Thioredoxin interacting protein (TXNIP) is an important regulator of redox processes. Activation and upregulation of TXNIP may play a central role in the mechanisms underlying arsenic-induced oxidative stress, inflammation, and cytotoxicity. Arsenic exposure has been shown to upregulate TXNIP expression, further amplifying oxidative stress, causes cellular damage. In the present study, the antioxidant potential of 50 phytochemicals from S. aromaticum and T. chebula, were screened using molecular docking studies against TXNIP, followed by MD simulations studies. The study revealed stigmasterol to exhibit the highest negative dock score and hence best binding affinity towards the target protein (TXNIP). The minimum binding energy of -10.14 Kcal/mol as compared to the fisetin with a binding energy of -7.15 Kcal/mol, the latter being selected as one of the standard drugs for our study. The MD simulation study of the stigmasterol-TXNIP complex for 100 Nanoseconds exhibited a stable interaction between protein-ligand thus validating our docking studies. The study also involved in vitro analysis of the best inhibitor of TXNIP uncovered in molecular docking studies. The in-vitro analysis demonstrated that stigmasterol pre-treatment conferred significant protection against Sodium Arsenite-mediated cytotoxicity in cultured Vero cells (African green monkey kidney cells). Furthermore, we employed 2'-7'-Dichlorodihydrofluorescein diacetate staining and captured fluorescent images, fluorescence images provided visual evidence supporting the cytoprotective role of stigmasterol, as evidenced by a reduction in oxidative stress compared to arsenic-treated cells.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102027"},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the leukocyte glucose index in predicting clinical outcomes in acute methanol toxicity.","authors":"Ola Elsayed Nafea, Walaa Gomaa Abdelhamid, Fatma Ibrahim","doi":"10.1016/j.toxrep.2025.101994","DOIUrl":"10.1016/j.toxrep.2025.101994","url":null,"abstract":"<p><strong>Introduction: </strong>Acute methanol poisoning signifies a global health issue. This study was designed to explore the role of the leukocyte glucose index (LGI) in predicting clinical outcomes; in-hospital mortality and visual impairment, and length of hospital stay, in acute methanol toxicity and to evaluate the association between LGI and all initial patient characteristics.</p><p><strong>Patients and methods: </strong>This was a retrospective analysis that involved 82 acutely methanol-intoxicated patients, starting from January 2021 to December 2023. Patients were categorized by on-admission LGI tertiles into low, intermediate, and high groups.</p><p><strong>Results: </strong>Approximately 27 % (22 out of 82) of patients died during hospitalization, with most of them belonging to the high LGI group. No significant differences existed in the proportions of patients with total vision loss, or the length of hospital stay. The majority of the undesirable findings were apparent in patients in either the intermediate or high LGI groups. LGI can distinguish exceptionally between survivors and non-survivors with an area under the curve of 0.808. However, LGI does not have any discriminatory power in predicting adverse visual outcomes.</p><p><strong>Conclusion: </strong>LGI can serve as a valuable tool in predicting early in-hospital mortality in acute methanol poisoning.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"101994"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into medication-induced liver injury: Understanding and management strategies.","authors":"Vatsalya Tiwari, Shrishti Shandily, Jessielina Albert, Vaibhav Mishra, Manoj Dikkatwar, Rohit Singh, Sujit Kumar Sah, Sharad Chand","doi":"10.1016/j.toxrep.2025.101976","DOIUrl":"10.1016/j.toxrep.2025.101976","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) has increasingly become a major concern in Western countries since the late 1960s, with an estimated annual incidence of 13.9-19.1 cases per 100,000 people. DILI is a significant cause of acute liver failure, exhibiting a high mortality rate of 10-50 %. Its etiology includes medications, herbal products, and dietary supplements, exacerbated by pre-existing liver conditions, sonorities, pregnancy, and nutritional deficiencies. It is categorized into intrinsic and idiosyncratic reactions. Intrinsic DILI, dose-dependent and predictable, is primarily caused by substances like paracetamol, which leads to liver toxicity through direct metabolic pathways. In contrast, idiosyncratic DILI is less common, unpredictable, and affects susceptible individuals, with non-steroidal anti-inflammatory drugs, antibiotics, and cardiovascular agents frequently implicated in hospitals. Oxidative stress, mitochondrial dysfunction, bile salt export inhibition, and stress on the endoplasmic reticulum are some DILI-related pathophysiology. Diagnosis relies on biochemical tests, serological markers, radiological investigations, and liver biopsy. Management strategies emphasize the identification and cessation of the offending drugs, supportive care, and specific treatment options targeted to the culprit drugs. Management depends on the severity and nature of the injury.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"101976"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico, in vitro and in vivo toxicity assessment of the antitumoral peptide GK-1","authors":"Sergio Sifontes-Rodríguez ,&nbsp;Juan Alberto Hernández-Aceves ,&nbsp;Carlos Gerardo Salas- Garrido ,&nbsp;Diego Moctezuma Rocha ,&nbsp;Iván Nicolás Pérez-Osorio ,&nbsp;Nelly Villalobos ,&nbsp;Edda Sciutto ,&nbsp;Gladis Fragoso","doi":"10.1016/j.toxrep.2025.101962","DOIUrl":"10.1016/j.toxrep.2025.101962","url":null,"abstract":"<div><div>Peptide drugs have emerged as an attractive alternative for cancer treatment due to their potency, high specificity, general safety and low cost. GK-1 is a linear 18 amino acid peptide with proven immunomodulator, antitumor and antimetastatic capacity in animal models. Preclinical toxicity studies for its use as a vaccine adjuvant demonstrated its safety in various assay systems, but a comprehensive exploration of its toxicity profile is required to be used in cancer immunotherapy. Therefore, in the present work, the potential toxicity of GK-1 was predicted with ToxinPred 3.0 software, and its <em>in vitro</em> cytotoxicity, and single-dose and repeated-dose toxicity by subcutaneous route in mice were experimentally assessed. GK-1 peptide was predicted as a non-toxic and did not exhibit <em>in vitro</em> cytotoxicity for several non-tumor and tumor cell lines and primary cell cultures at concentrations up to 500 µM, reinforcing previous studies pointing that the antitumoral effect of GK-1 was not mediated by tumor cell cytotoxicity. The single-dose toxicity study did not evidence local or systemic toxicity up to the maximum tested dose of 1000 mg/kg. Moreover, no toxic effects were observed in the repeated-dose toxicity study based on four doses administered weekly at up to 300 mg/kg. Considering that GK-1 is effective in triple-negative breast cancer and melanoma models in mice at doses as low as 5 mg/kg, the present results support the safety of GK-1 as an antitumoral peptide candidate.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101962"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: “Co-delivery of methotrexate and berberine based on PAMAM dendrimers for targeting HeLa cancer cells” [Toxicol. Rep. Volume 13, December 2024, 101765]","authors":"Hossein Majidzadeh ,&nbsp;Mostafa Araj-Khodaei ,&nbsp;Ayuob Aghanejad ,&nbsp;Maryam Ghaffari ,&nbsp;Amir Jafari ,&nbsp;Forough Jenanifard ,&nbsp;Jafar Ezzati Nazhad Dolatabadi ,&nbsp;Hashem Andishmand ,&nbsp;Michael R. Hamblin","doi":"10.1016/j.toxrep.2025.101957","DOIUrl":"10.1016/j.toxrep.2025.101957","url":null,"abstract":"","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101957"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus","authors":"Fouad Kasim Mohammad ,&nbsp;Rawnaq Faris Al-Shalchi","doi":"10.1016/j.toxrep.2025.101958","DOIUrl":"10.1016/j.toxrep.2025.101958","url":null,"abstract":"<div><div>Dyslipidemic statins reduce blood and brain cholinesterase (ChE) activities in mice, with scarce information on other protein/enzyme targets. The study aims at conducting a mini meta-analysis on <em>in vivo</em> and <em>in vitro</em> adverse anti-ChE effects of atorvastatin, simvastatin and rosuvastatin in mice, and using the SwissPrediction to identify <em>in silico</em> body target proteins. The data comprised 72 records of plasma, erythrocytes and brain ChE activities, expressed as percent mean ± SD of respective controls. We conducted a randomized effects size single-arm meta-analysis. The risk of bias scoring was according to those of animal experiments. The effect size (% ChE activity) of statin treatments was significantly decreased by 25.85 % (combined effect size=74.15, p = 0.0001), with significant heterogeneity (<em>Q</em>=1133.19, p &lt; 0.0001, I²=93.73 %). Subgroup analysis was significantly dose and concentration-dependent. The funnel plot showed non-symmetrical data distribution, with no imputed points. The risk of bias was moderate. <em>In silico</em> mouse body protein targets for the statins were mainly classes of Family AG protein- coupled receptor (20.0 %-33.3 %), Oxidoreductase (6.7–13.3 %) and Eraser (13.3 % each), with others at 0–26.7 %. The findings highlight statin effects in mice by reducing blood and brain ChE activities, in a dose/concentration-dependent manner, that would potentially modulate the cholinergic system. This anti-ChE effect together with <em>in silico</em> protein targets recognized could be the basis of further experimental explorations of adverse effects of statins.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101958"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of Allium sativum essential oil against lead nitrate-induced cardiotoxicity: Modulation of lipid metabolism, nitric oxide dynamics, inflammatory mediators, and histological profiles in Swiss albino mice","authors":"Anjali Rajpoot ,&nbsp;Veena Sharma","doi":"10.1016/j.toxrep.2025.101950","DOIUrl":"10.1016/j.toxrep.2025.101950","url":null,"abstract":"<div><h3>Background</h3><div>Lead (Pb²⁺) is a toxic metal known to induce oxidative stress and inflammation, contributing to cardiovascular diseases such as hypertension and atherosclerosis. Natural compounds like Allium sativum essential oil (ASEO) offer potential therapeutic benefits against lead-induced damage, but their cardioprotective effects remain underexplored. This study investigates the efficacy of ASEO in mitigating cardiovascular toxicity induced by lead nitrate in male Swiss albino mice.</div></div><div><h3>Methods</h3><div>Thirty-six male mice were divided into six groups: Control, Lead Nitrate (50 mg/kg), Lead Nitrate + Low-dose ASEO (50 mg/kg), Lead Nitrate + High-dose ASEO (80 mg/kg), Lead Nitrate + Silymarin (25 mg/kg), and Lead Nitrate + Olive Oil. After 12 days of lead exposure, treatments were administered for 30 days. Key cardiovascular parameters such as lipid profiles (total cholesterol, LDL, HDL), nitric oxide (NO), and inflammatory markers (TNF-α, IL-6, IFN-γ, IL-10, NF-κB) were evaluated alongside histological analysis of cardiac tissue.</div></div><div><h3>Results</h3><div>Lead nitrate exposure significantly increased total cholesterol (88.27 µg/mL) and LDL (93.78 µg/mL) while reducing HDL (17.51 µg/mL) compared to controls (<em>P</em> &lt; 0.001). High-dose ASEO lowered total cholesterol (66.07 µg/mL) and LDL (49.62 µg/mL) while increased HDL (27.2 µg/mL) (<em>P</em> &lt; 0.001). NO levels, reduced by lead exposure, were significantly restored by high-dose ASEO (<em>P</em> &lt; 0.001). Inflammatory markers, including TNF-α, NF-kB, and IL-6, were elevated in the lead group but decreased significantly following ASEO treatment (<em>P</em> &lt; 0.001). Histological analysis showed that ASEO markedly preserved myocardial architecture, reducing degeneration and inflammation.</div></div><div><h3>Conclusion</h3><div>High-dose ASEO demonstrated significant cardioprotective effects against lead-induced toxicity by improving lipid profiles, enhancing NO levels, and modulating inflammatory markers. Further studies are warranted to validate these results.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101950"},"PeriodicalIF":0.0,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}