Toxicology Reports最新文献

{"title":"Liver disorders and phytotherapy.","authors":"Syed Sanober Qadri, Darakhshan Javaid, Adfar Reyaz, Shahid Yousuf Ganie, Mohd Salim Reshi","doi":"10.1016/j.toxrep.2025.102047","DOIUrl":"10.1016/j.toxrep.2025.102047","url":null,"abstract":"<p><p>The liver is an essential organ crucial for metabolism, detoxification, and maintaining homeostasis, faces growing global health challenges such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), hepatitis, cirrhosis, and liver cancer. These conditions collectively account for significant morbidity and mortality worldwide. Although traditional treatments help control symptoms and slow disease progression, they are frequently hindered by issues such as drug resistance, side effects, and high costs, especially in areas with limited resources. Drug-induced liver injury (DILI) continues to be a significant concern. Traditional medicine offers a promising avenue for addressing these limitations, with numerous plants demonstrating hepatoprotective properties through their bioactive compounds, including alkaloids, glycosides, and flavonoids. These natural agents not only mitigate hepatic damage but also provide immune modulation and chronic disease management. This review examines liver injury mechanisms and highlights the therapeutic potential of traditionally used medicinal plants in treating and preventing the liver diseases, emphasizing the integration of traditional knowledge with modern pharmacological advancements.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102047"},"PeriodicalIF":0.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249742","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 global DNA methylation in citrinin induced toxicity: <i>In vitro</i> and <i>in silico</i> approach.","authors":"Metin Caner Cakir, Sibel Ozden","doi":"10.1016/j.toxrep.2025.102046","DOIUrl":"10.1016/j.toxrep.2025.102046","url":null,"abstract":"<p><p>Citrinin (CIT) is a widely occurring mycotoxin which exhibits a variety of toxic effects. Only a few countries have legal limitations on CIT content in foods, despite the dangers it presents. The aim of this study is to investigate the effects of CIT on DNA methylation in SH-SY5Y and HK-2 cells and to perform docking studies to explore the possible interactions between CIT and DNMT enzymes. In SH-SY5Y cells, global DNA methylation levels increased by 1.90-fold (p < 0.05) and 1.50-fold (p < 0.05) at 50 and 100 μM of CIT, respectively. In HK-2 cells, the increase was 3.17-fold (p < 0.05) following exposure to 50 μM of CIT. In SH-SY5Y cells, <i>DNMT-1</i>, <i>DNMT-3a</i>, <i>DNMT-3b</i> and <i>TET-3</i> expressions increased significantly, while <i>TET-1</i> and <i>TET-2</i> expressions decreased significantly. In HK-2 cells, no significant change in <i>DNMT-1</i> expression was observed, while <i>DNMT-3a</i> and <i>DNMT-3b</i> expressions increased significantly. Significant decreases in <i>TET-1</i>, <i>TET-2</i> and <i>TET-3</i> expressions were observed in HK-2 cells. The docking results suggest that CIT may interact with DNMTs with a high degree of binding, which could potentially lead to the inhibition of these enzymes. The results of this study indicate that DNA methylation may be involved in CIT-induced toxicity. Epigenetic mechanisms and <i>in silico</i> studies hold great potential for advancing chemical risk assessment by uncovering toxicity mechanisms, and the standardization of these techniques is crucial for their integration into policymaking. Accordingly, this study introduces a novel aspect of the potential mechanism of CIT in the risk assessment process.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102046"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249745","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":"Lead neurotoxicity in experimental models: A systematic review on effects on the cerebrum, cerebellum, and hippocampus.","authors":"Fredrick Ohiomokhai Tobalu, Adaze Bijou Enogieru","doi":"10.1016/j.toxrep.2025.102044","DOIUrl":"10.1016/j.toxrep.2025.102044","url":null,"abstract":"<p><p>The extensive use of heavy metals, such as lead, has resulted in environmental damage and numerous health problems in many parts of the world. Reports indicate that lead is the most significant toxic heavy metal with adverse impacts on several body systems. Primarily, lead targets the nervous system and causes a variety of neurological, motor, and behavioral deficits in humans and laboratory animals. Although several reports demonstrate the toxicity of lead, there is a paucity of comprehensive and updated reviews to highlight various histopathological findings on the effects of lead and its mechanisms of action on different brain structures; accordingly, this review was designed to address this gap. To achieve this, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system was utilized, and prominent scientific databases, including Scopus, Web of Science, ResearchGate, Science Direct, Pubmed, and Google Scholar were searched to obtain information on the effects of lead and its mechanisms of action on different brain regions. Initially, 133 articles were obtained, but 60 articles satisfied the inclusion criteria and were selected for this review. These findings provide an updated compilation of lead toxicity and its mechanisms of action on different brain structures in experimental models. In addition, this review helps to advance the comprehension of lead poisoning and its harmful effects on the brain and may aid in the search for the development of novel therapeutic agents capable of mitigating lead toxicity and its associated neurological disorders.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102044"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249741","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":"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":"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}

{"title":"Environmental health risks and impacts of PM2.5 exposure on human health in residential areas, Bantul, Yogyakarta, Indonesia","authors":"Azham Umar Abidin ,&nbsp;Anisful Lailil Munawaroh ,&nbsp;Aulia Rosinta ,&nbsp;Arvi Tri Sulistiyani ,&nbsp;Iwan Ardianta ,&nbsp;Fajri Mulya Iresha","doi":"10.1016/j.toxrep.2025.101949","DOIUrl":"10.1016/j.toxrep.2025.101949","url":null,"abstract":"<div><div>Air pollution, particularly PM_2.5, significantly impacts public health in developing areas. This study evaluates PM_2.5 exposure among residents and conducts a health risk assessment within the human community in Bantul Regency, Indonesia, utilizing a high-volume air sampler (HVAS) over 24 h in a residential area and interviewing 36 respondents. The findings of this study show that PM_2.5 concentrations varied from 50.7 to 61.9 μg/m³, exceeding the national ambient air quality standards (NAAQS) of 35 μg/m³. The risk hazard quotient (RQ) values of PM_2.5 were greater than 1, signifying considerable health risk. Epidemiological statistical analysis indicates a significant correlation (p-value &lt; 0.05) between PM_2.5 exposure, health complaints, and respondent characteristics. Residents report health issues including cough, headache, eye irritation, breathlessness, and wheezing. The findings emphasize the imperative for more rigorous air quality standards and regulations, enhanced public awareness and education regarding preventive practices, and urban planning development strategies incorporating green infrastructure. These measures are crucial for alleviating health hazards and enhancing air quality in impacted areas.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101949"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379150","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}