Toxicology Reports最新文献

{"title":"Phenolic-rich fraction of <i>Solanum betaceum</i> mitigates atorvastatin-induced myotoxicity through antioxidant mechanisms in female wistar rats.","authors":"Rachael Jackie Mpumbya, Josiah Eseoghene Ifie, Ayomide Victor Atoki, Stella Maris Kembabazi, Solomon Adoni Mbina, Eliah Kwizera, Gilbert Akankwasa, Mary Gorret Ablinda, Fred Bwamble, Siida Robert, Pastori Mujinya, Andrew Kisakye, Ilemobayo Victor Fasogbon, Nancy B Mitaki, Ibrahim Babangida Abubakar, Daniel Ejike Eze, Nwokike Matthew Onyemaechi, Sana Noreen, Patrick Maduabuchi Aja","doi":"10.1016/j.toxrep.2025.102049","DOIUrl":"10.1016/j.toxrep.2025.102049","url":null,"abstract":"<p><strong>Background: </strong>Atorvastatin, a widely prescribed cholesterol-lowering medication, has been linked to statin-induced myotoxicity, a condition marked by elevated muscle enzymes and oxidative stress. While statins are essential for managing hypercholesterolemia and preventing cardiovascular diseases, their myotoxic side effects limit broader clinical use. This study investigated the myo-protective effects of the phenolic-rich fraction of <i>Solanum betaceum</i> (PRFSB) in mitigating atorvastatin-induced muscle damage in female Wistar rats.</p><p><strong>Methods: </strong>Thirty female Wistar rats were divided into five groups: (1) a true control group receiving distilled water, (2) an atorvastatin-only group, and three treatment groups receiving PRFSB at varying doses (100, 200, and 400 mg/kg) alongside atorvastatin. Muscle enzymes (creatine kinase and lactate dehydrogenase), oxidative stress markers (catalase, superoxide dismutase, and malondialdehyde), and histopathological changes were assessed.</p><p><strong>Results: </strong>Atorvastatin significantly elevated serum CK, LDH and oxidative stress markers, while PRFSB administration, particularly at 400 mg/kg, significantly reduced these elevations (p < 0.05). PRFSB restored muscle enzyme levels, normalized antioxidant defenses and reduced lipid peroxidation. Histological analysis revealed that PRFSB-treated groups exhibited preserved muscle architecture with minimal inflammation.</p><p><strong>Conclusion: </strong>PRFSB effectively alleviated atorvastatin-induced myotoxicity by reducing oxidative stress, restoring muscle biomarkers and protecting tissue integrity. These findings suggest that PRFSB holds promise as an adjunct therapy to mitigate statin-induced muscle toxicity, warranting further exploration in clinical settings.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102049"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259006","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 vitro</i> to <i>in vivo</i> evidence for chemical disruption of glucocorticoid receptor signaling.","authors":"Maeve T Morris, Jordan L Pascoe, Jonathan T Busada","doi":"10.1016/j.toxrep.2025.102053","DOIUrl":"10.1016/j.toxrep.2025.102053","url":null,"abstract":"<p><p>Glucocorticoids are steroid hormones that regulate stress homeostasis, metabolism, and inflammatory responses. Dysregulation of the glucocorticoid receptor (GR) is linked to diseases such as obesity, mood disorders, and immune dysfunction. Endocrine-disrupting chemicals (EDCs) are widespread environmental contaminants known to interfere with hormone signaling, but their impact on glucocorticoid signaling remains unclear. While several GR-disrupting compounds have been identified <i>in vitro</i>, their <i>in vivo</i> effects remain largely unknown. In this study, we identified the agricultural agents dichlorodiphenyltrichloroethane (DDT) and ziram as GR-disruptors <i>in vitro</i>. <i>In vivo</i>, corticosterone co-treatment with DDT or the GR antagonist RU-486 inhibited the expression of classic GR-regulated transcripts in the liver. Furthermore, chronic exposure to DDT or RU-486 significantly reduced circulating B lymphocyte populations. These findings underscore the need to translate <i>in vitro</i> discoveries into <i>in vivo</i> models to assess the clinical relevance of GR-disrupting compounds. Moreover, they highlight the potential for xenobiotic-induced GR disruption to impair metabolic and immune homeostasis, potentially increasing disease susceptibility.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102053"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259005","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":"Nutrients and toxic heavy metals in <i>Strychnos cocculoides</i> (Loranthaceae): Implications for traditional medicine.","authors":"Bitwell Chibuye, Indra Sen Singh, Luke Chimuka, Mokgaetji Monyai","doi":"10.1016/j.toxrep.2025.102050","DOIUrl":"10.1016/j.toxrep.2025.102050","url":null,"abstract":"<p><p>This study investigates the medicinal and toxicological profiles of <i>Strychnos cocculoides,</i> used in traditional medicine in Zambia, focusing on its nutrient content and heavy metal accumulation. Metals were extracted from dried plant samples using microwave digestion, and metal concentrations were determined using inductively coupled plasma optical emission spectrometry (ICP-OES). The concentrations of key nutrients such as calcium (Ca), potassium (K), and magnesium (Mg) were quantified in the plant's root, stem, and leaves, revealing its medicinal potential. However, some heavy metals were detected at concentrations above recommended values, raising concerns about health risks. Elevated metal concentrations in the plant include cadmium (Cd) at 2.8 mg/kg in the root and stem and 3.0 mg/kg in the leaf, exceeding the 0.3 mg/kg WHO/FAO limit; chromium (Cr) at 60.4 mg/kg in the root and 29.8 mg/kg in the stem, surpassing the 25.0 mg/kg guideline; iron (Fe) at 15,433.0 mg/kg in the root and 1421.8 mg/kg in the leaf, far exceeding the 425.5 mg/kg limit; and manganese (Mn) at 379.6 mg/kg in the root, 963.0 mg/kg in the stem, and 2069.0 mg/kg in the leaf, which exceeds the 200 mg/kg threshold. Toxicological profiling predicted neurotoxicity and ecotoxicity for aluminum (Al), Cd, Cr, and nickel (Ni), with a particular focus on their ability to cross the blood-brain barrier and cause long-term damage. While <i><b>S. cocculoides</b></i> offers medicinal benefits, its heavy metal content poses significant health risks, necessitating further research on safe processing techniques and its role in environmental management. These findings emphasize caution in traditional medicine and the plant's potential for human health and environmental remediation.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102050"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249744","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":"Plasma phthalate levels in children with speech delay.","authors":"Nihal Yaman Artunç, Anıl Yirün, Gizem Yıldıztekin, Pınar Erkekoğlu, Pınar Zengin Akkuş, Evin İlter Bahadur, Gökçenur Özdemir, Elif N Özmert","doi":"10.1016/j.toxrep.2025.102052","DOIUrl":"10.1016/j.toxrep.2025.102052","url":null,"abstract":"<p><p>Speech delay is a common developmental concern. Environmental pollutants like phthalates, recognized as endocrine disruptors, may be a risk factor. We aimed to investigate the relationship between phthalates and speech delay. The study comprised 50 children with isolated speech delay and 40 healthy children of similar ages. Children were assessed for speech delay risk factors and phthalate exposure sources. High-pressure liquid chromatography examined plasma di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP) and dibutyl phthalate (DBP) levels. DEHP, MEHP, and DBP levels varied between study and control groups: 0.377 (0.003-1.224 µg/ml), 0.212 (0.007-1.112 µg/ml) (p = 0.033), 0.523 (0.031-2.477 µg/ml), 0.152 (0.239-2.129 µg/ml) (p < 0.001), and 0.395 (0.062-1.996 µg/ml) and 0.270 (0.006-0.528) (p = 0.004). Multiple linear regression was used to adjust phthalate levels and speech delay risk factors. DEHP levels were did not differ significantly between the groups (p = 0.233), whereas MEHP and DBP levels were considerably higher in the study group (p < 0.001). The statistically significant rise in plasma phthalate levels in children with speech delay implies phthalate exposure may be a risk factor, but further epidemiological research is needed.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102052"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259007","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":"Molecular signatures of xenograft colorectal cancer in mice treated with topotecan: A mass spectrometry-based study.","authors":"Yousra A Hagyousif, Ruba A Zenati, Nelson C Soares, Hamza M Al-Hroub, Farman Matloob Khan, Rizwan Qaisar, Rifat Hamoudi, Raafat El-Awady, Ahmad Y Abuhelwa, Wafaa Ramadan, Waseem El-Huneidi, Eman Abu-Gharbieh, Karem H Alzoubi, Yasser Bustanji, Mohammad H Semreen","doi":"10.1016/j.toxrep.2025.102045","DOIUrl":"10.1016/j.toxrep.2025.102045","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is one of the most common cancers worldwide, yet it continues to have a low survival rate, largely due to the lack of effective treatments. Metabolomics offers new insight into disease diagnosis and biomarkers discovery. The aim of the study is to identify serum biomarkers in a CRC xenograft mouse model treated with topotecan using advanced metabolomics techniques to enhance our understanding and management of the disease.</p><p><strong>Methods: </strong>The therapeutic potentials of the anticancer drug topotecan on metabolomic alterations in CRC were explored using the UHPLC-ESI-QTOF-MS platform. A comprehensive metabolomic analysis was conducted to compare four different animal groups: HCT-116 CRC xenograft mice treated with topotecan (treated group), vehicle-control HCT-116 xenograft mice (untreated CRC xenograft mice), positive controls (healthy mice injected with topotecan), and negative controls (healthy mice).</p><p><strong>Results: </strong>The study identified 53 altered metabolites across all four groups (<i>p-value</i> < 0.05). Independent T-test revealed that 15 metabolites were statistically significant among vehicle controls and negative controls. Additionally, 20 metabolites showed significant differences between the potential responders to topotecan and the vehicle controls. Moreover, only one metabolite was statistically significant between the positive and negative controls.</p><p><strong>Conclusion: </strong>The findings provide a detailed characterization of metabolic alterations associated with topotecan treatment in CRC. These insights contribute to a better understanding of the drug's mechanism of action, which may help predict CRC patients' response to topotecan and guide the development of personalized therapeutic strategies.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102045"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267285","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":"Preclinical efficacy and safety assessments of Adult human neural stem cells (AhNSCs) for spinal cord injury.","authors":"Young-Do Kwon, Jeong-Seob Won, Xiangyu Ma, Yoon Jung Choi, Kyoung-Sik Moon, Sang-Jin Park, Eun-Young Gu, Hyeon-Kyu Go, Myung-Jin Kim, Yong-Ho Kim, Geun-Hyoung Ha, Hyun Nam, Chung Kwon Kim, Sungjoon Lee, Sun-Ho Lee, Kyeung Min Joo","doi":"10.1016/j.toxrep.2025.102048","DOIUrl":"10.1016/j.toxrep.2025.102048","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a severe and devastating condition that leads to irreversible damage to neural tissues, creating significant medical, economic, and social challenges. The ability to differentiate into multiple neural cell types and to regulate immune response makes neural stem cells (NSC) a promising strategy for treating SCI. In this study, we investigated the therapeutic potential, safety profile, and tumorigenic risk of intrathecally transplanted adult human neural stem cells (AhNSCs) produced under clinical-grade standards in a Good Manufacturing Practice (GMP) facility, in rat SCI models, thereby laying the foundation for future clinical trials. Functional tests, including the Basso, Beattie, and Bresnahan (BBB) locomotor rating, rotarod, and von Frey tests, showed significant improvements in motor function and mechanical sensitivity in rats with SCI. Histological analysis revealed reduced tissue loss, glial scar formation, and increased axonal regeneration. Biodistribution studies indicated that the transplanted AhNSCs are primarily localized within the spinal cord, with minimal systemic distribution. Toxicity studies found no significant adverse effects, suggesting a favorable safety profile. Long-term tumorigenicity studies reported no treatment-related deaths or signs of tumor formation in either gender. In conclusion, the study demonstrates that AhNSCs offer promising therapeutic potential for treating SCI, contributing to improved motor function and sensory recovery. These findings support further investigation and potential clinical applications of AhNSCs for treating SCI and related neurological disorders.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102048"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267286","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":"Micro- and nanoplastic toxicity in humans: Exposure pathways, cellular effects, and mitigation strategies.","authors":"Faezeh Jahedi, Neamatollah Jaafarzadeh Haghighi Fard","doi":"10.1016/j.toxrep.2025.102043","DOIUrl":"10.1016/j.toxrep.2025.102043","url":null,"abstract":"<p><p>Microplastics and nanoplastics (MNPs) are emerging environmental contaminants with increasing scientific evidence suggesting their potential risks to human health. The present review systematically explores the pathways through which these particles enter the human body, the cellular and molecular mechanisms of their toxicity, and current strategies to mitigate their effects. A structured literature review was conducted following PRISMA guidelines, focusing on studies published between 2019 and 2024 across major scientific databases. MNPs primarily enter the human system via ingestion, inhalation, and dermal exposure. Once internalized, they can accumulate in various organs and trigger oxidative stress, inflammation, apoptosis, and genotoxic effects. These toxic responses have been linked to chronic conditions such as metabolic disorders (e.g., diabetes, obesity), immune dysfunction, and neurodegenerative diseases. Furthermore, this review highlights emerging attenuation strategies, including advanced filtration technologies, bioremediation approaches, and bioactive compounds such as melatonin, astaxanthin, and probiotics. By identifying exposure pathways, toxic effects, and current research gaps, this review provides a comprehensive foundation for developing effective interventions to reduce MNP-related health risks and inform future toxicological studies.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102043"},"PeriodicalIF":0.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249743","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":"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}