Drug and Chemical Toxicology最新文献

{"title":"Vitamin E improves oxidative stress, apoptosis, and steroidogenesis impairment in glyphosate-induced mice.","authors":"Mehdi Shafiee Mehr, Seyed Mohammad Jafar Haeri, Mitra Barzroodi Pour, Mohammad Bayat","doi":"10.1080/01480545.2024.2417954","DOIUrl":"10.1080/01480545.2024.2417954","url":null,"abstract":"<p><strong>Background: </strong>Glyphosate (Gly) is a nonselective pesticide with high potential to toxic effects on the reproductive system. Recent studies suggest that Vitamin E can indeed have a positive impact on the reproductive system, while Gly, a nonselective pesticide, has been linked to significant risks of toxicity on reproductive health. It's crucial to be mindful of the potential impacts of such substances on the reproductive system.</p><p><strong>Methods: </strong>Seventy female mice were categorized into seven groups.: (1) control, (2) olive oil (as Vit E solvent), (3) Vit E, (4) L-Gly, (5) H-Gly, (6) L-Gly + Vit E, and (7) H-Gly + Vit E. Various factors related to oxidative stress, antioxidant activity, steroid hormones, and mRNA expression levels of genes involved in apoptosis and steroidogenesis were assessed.</p><p><strong>Results: </strong>After treatment with both doses of Gly, the malondialdehyde level significantly increased in comparison to the control group. Conversely, the activity of catalase and the levels of glutathione, estrogen, and progesterone decreased. Treatment of mice with both doses of Gly resulted in increased mRNA levels of Bax, caspase-3, and caspase-9 genes, as well as a decreased mRNA level of the Bcl-2 gene and factors involved in steroidogenesis (StAR and 3-β-HSD) comparison to the control group.</p><p><strong>Conclusion: </strong>These results offer that vitamin E could help improve some of the adverse effects of Gly in the ovaries of female mice.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"903-911"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of acute and 28-day repeated dose toxicity of <i>Tolypocladium sinense</i> soft capsule in Sprague-Dawley rats.","authors":"Xu Feng, Song Chen, Jinfeng Li, Xiaoyu Dai, Yun Chen, Bin Xie, Zhenzhen Zhang, Lijun Ren, Lang Yan","doi":"10.1080/01480545.2024.2427766","DOIUrl":"10.1080/01480545.2024.2427766","url":null,"abstract":"<p><p><i>Tolypocladium sinense</i> is a new asexual strain isolated from natural <i>Cordyceps sinensis</i>. The mycelium produced by its fermentation culture has similar chemical components and pharmacological effects to <i>C. sinensis. T. sinense</i> soft capsule is primarily prepared from <i>T. sinense</i> mycelium, which is mainly used for the treatment of body damage induced by low-dose ionizing radiation. However, its potential toxicity remains unclear. This study was designed to assess the toxicological characteristics of <i>T. sinense</i> soft capsules through acute and 28-day repeated dose toxicity studies. In the acute toxicity study, no toxic symptoms or mortality were observed in rats following a single oral administration of 10 000 mg/kg of <i>T. sinense</i> soft capsules. The maximum tolerated dose for a single oral dose of <i>T. sinense</i> soft capsules in rats was over 10 000 mg/kg. During the repeated dose toxicity test, oral administration of 90, 360, and 1440 mg/kg/day of <i>T. sinense</i> soft capsules for 28 consecutive days did not lead to significant toxic effects in rats. The no observed adverse effect level in rats surpassed 1440 mg/kg/day. These results provide preliminary evidence that <i>T. sinense</i> soft capsules are relatively safe.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1045-1056"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicogenetic profile and antioxidant evaluation of gamma-terpinene: Molecular docking and <i>in vitro</i> and <i>in vivo</i> assays.","authors":"Railson Pereira Souza, Antonielly Campinho Dos Reis, Vinícius Duarte Pimentel, Bianca de Sousa Leal, Milena Monteiro de Freitas, Jefferson da Cruz Esteves, Lara Priscila Freitas Ferreira, Débora Caroline do Nascimento Rodrigues, Rayran Walter Ramos de Sousa, Alyne Pereira Lopes, Maria José Dos Santos Soares, João Marcelo de Castro E Sousa, Paulo Michel Pinheiro Ferreira, Aldeídia Pereira de Oliveira","doi":"10.1080/01480545.2025.2499939","DOIUrl":"10.1080/01480545.2025.2499939","url":null,"abstract":"<p><p>Gamma-terpinene (γ-TPN) is found in several plant species, such as thyme, eucalyptus, rosemary, black cumin, oregano, among others, and is known for antimicrobial, antiparasitic, antinociceptive, anticancer, antiplatelet, and insecticidal activities. Based on this, it was assessed its toxicogenetic and antioxidant profile using <i>in silico</i>, <i>in vitro</i> and <i>in vivo</i> replacement assays. The compound was moderately toxic on <i>Artemia salina</i> nauplii [LC₅₀ value of 136.1 (81.8 - 158.7) µM] and reduced proliferation of melanoma B16-F10 [IC₅₀ value of 38.19 (26.82 - 54.52) μM] tumor cells, without affecting viability of normal RAW 264.7 macrophages and mammalian erythrocytes' membrane. γ-TPN (12.5, 25 and 50 µM) intensively reduced the mitotic index (MI) of dividing <i>Allium cepa</i> meristematic cells in a non-concentration-dependent way and caused increasing in interphase and reduction in prophase cells (p < 0.05). The monoterpene showed <i>in silico</i> affinity to the enzymes catalase and glutathione reductase and <i>in vivo</i> amplification of the catalase activity in erythrocytes of γ-TPN-treated spontaneous hypertensive rats. Increase of binucleated cells was observed at the highest dose (100 mg/kg/day) only. Then, as a natural molecule, γ-TPN isn't free of damaging effects, and further investigations are needed to ensure limiting doses and regulation aspects.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"959-971"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurine and enzymatically modified isoquercitrin synergistically protect against the methotrexate-induced cardiotoxicity in rats: antioxidant and antiapoptotic effects.","authors":"Marwa M Mahmoud, Rehab Hegazy, Wael M El-Sayed","doi":"10.1080/01480545.2024.2424282","DOIUrl":"10.1080/01480545.2024.2424282","url":null,"abstract":"<p><p>This study aimed to evaluate the protective potential of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ), both individually and in combination, against MTX-induced cardiotoxicity in male rats. A total of 36 rats were randomly divided into six groups (six animals each): control (vehicle), MTX alone (20 mg/kg, single dose), EMIQ+MTX (EMIQ at 26 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), Tau + MTX (Tau at 500 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), (EMIQ+Tau)+MTX, and (EMIQ+Tau)½+MTX. MTX treatment resulted in elevated levels of cardiac creatine phosphokinase-myocardial band, troponin I, nitric oxide, malondialdehyde, and serum IL-6, while decreasing levels of cardiac myeloperoxidase, catalase, and superoxide dismutase. MTX also reduced expression of <i>BMI-1</i>, induced DNA laddering and fragmentation, and increased cleaved caspase-3 protein expression in cardiac tissue. Both Tau and EMIQ showed equivalent effectiveness in protecting the heart against MTX-induced damage due to their antioxidant, anti-inflammatory, and antiapoptotic properties. Notably, combined treatment with half-doses of Tau and EMIQ offered superior protection compared to full doses of each agent alone. The full-dose combination showed similar efficacy to the half-dose combination, with a few exceptions. Overall, these results suggest a synergistic effect of Tau and EMIQ in mitigating MTX-induced cardiotoxicity, warranting further investigation into the underlying mechanisms.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1025-1034"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascorbic acid regulates <i>in vitro</i> and <i>in vivo</i> toxicogenetic effects of hydroxyurea on eukaryotic cells.","authors":"Raí Pablo Sousa de Aguiar, Jéssica Maria Teles Souza, Ag-Anne Pereira Melo de Menezes, Maria Luísa Lima Barreto do Nascimento, João Marcelo de Castro E Sousa, Ana Amélia de Carvalho Melo Cavalcante, Paulo Michel Pinheiro Ferreira, Ana Jérsia Araújo, José Delano Barreto Marinho-Filho","doi":"10.1080/01480545.2024.2425990","DOIUrl":"10.1080/01480545.2024.2425990","url":null,"abstract":"<p><p>Hydroxyurea (HU) exerts unique and diverse biological effects as an anti-leukemic agent, irradiation sensitizer, and HbS inducer in patients with sickle cell anemia. Herein, we assessed the potential toxicogenic and/or oxidant effects of hydroxyurea associated with ascorbic acid by <i>in vivo</i> examinations in <i>Allium cepa</i> and human cancer cells and systemically on mice tissues. Growing <i>A. cepa</i> roots and HCT-116 colorectal tumor cells were examined after HU and HU plus ascorbic acid exposure. DNA damage and antioxidant enzymatic activity were quantified in peripheral blood mononuclear cells (PBMC), bone marrow leukocytes and livers of mice after 7 day-HU treatment (7.5, 15 and 30 mg/kg/day) and Vitamin C 2 μM. Hydroxyurea presented toxic effects on meristematic <i>Allium cepa</i> cells, causing chromosomal abnormalities and reduction of mitotic index, killed HCT-116 colorectal carcinoma cells and induced DNA injuries upon mice cells (hepatocytes, bone marrow leukocytes and PBMC). Simultaneously, hydroxyurea decreased levels of CAT and GSH activities and expand lipid peroxidation. All these biochemical and physiological changes were ameliorated when associated with ascorbic acid, indicating it restored antioxidant enzymes, decreased MDA levels, removed peroxides and, consequently, presented cytoprotection against HU-provoked cellular damage in normal cells. On the other hand, antioxidants compounds may interfere on effectiveness of HU during anticancer chemotherapies.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1035-1044"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach.","authors":"Prathap Srirangan, Evan Prince Sabina","doi":"10.1080/01480545.2025.2455442","DOIUrl":"10.1080/01480545.2025.2455442","url":null,"abstract":"<p><p>Cyclophosphamide is a key component of numerous chemotherapeutic protocols, demonstrating broad-spectrum efficacy against various malignancies and non-cancerous conditions. This review examines CPM's metabolic pathways, therapeutic applications, and its resulting organ-specific toxicities. Despite its clinical benefits in treating nephrotic syndrome, encephalomyelitis, breast cancer, ovarian cancer, and other diseases, CPM is associated with significant adverse effects on the kidneys, liver, heart, lungs, and intestines. The discussion delves into the molecular mechanisms underlying these toxicities, highlighting dysregulation in key signaling pathways, including Nrf2, NF-κB, MAPK/ERK, and AKT. In addressing these challenges, recent studies have identified various herbal drugs and phytochemicals capable of mitigating CPM-induced toxicity. Notable compounds such as cinnamaldehyde, baicalin, quercetin, and curcumin have demonstrated protective effects. Integrating these herbal formulations with CPM therapy is proposed to enhance patient safety and treatment efficacy. This review underscores the influence of CPM on apoptosis and inflammation pathways, which lead to alterations in organ-specific biomarkers. Phytochemicals may exert protective effects by restoring disrupted signaling pathways and normalizing altered biomarkers. The compilation of phytochemicals presented in this review serves as a valuable resource for researchers exploring other herbal products with potential protective effects against CPM toxicity. A significant gap in the current literature is the lack of clinical trials evaluating phytochemicals that mitigate CPM toxicity in vivo. Rigorous clinical studies are necessary to establish the efficacy and safety of herbal formulations in cancer treatment. Such research will clarify the role of natural remedies in complementing conventional therapies, ultimately improving patient outcomes.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"972-1014"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisphenol A exposure and its impact on childhood obesity: a molecular and genetic perspective.","authors":"Lili Chen, Limei Sun","doi":"10.1080/01480545.2025.2553869","DOIUrl":"https://doi.org/10.1080/01480545.2025.2553869","url":null,"abstract":"<p><p>Childhood obesity is a growing public health concern, with emerging evidence suggesting that environmental factors like bisphenol A (BPA) exposure may contribute to its development. This study aims to elucidate the genetic and molecular mechanisms linking BPA exposure to childhood obesity. We analyzed the publicly available dataset GSE9624 to identify differentially expressed genes (DEGs) associated with childhood obesity. We cross-referenced these DEGs with BPA-related toxicity targets obtained from the Comparative Toxicogenomics Database (CTD) and SwissTargetPrediction database. Network construction, molecular docking, enrichment analysis, Gene Set Variation Analysis (GSVA), and correlation analysis were performed to explore interactions between BPA exposure and childhood obesity. We identified 967 DEGs associated with childhood obesity, with 81 overlapping BPA-related toxicity targets. A heatmap revealed distinct expression patterns of these genes between obese and normal-weight children. Network analysis highlighted JUN, TOP2A, APOE, and LEP as hub genes. Molecular docking indicated strong binding affinities between BPA and these core targets. Enrichment analysis revealed disruptions in lipid metabolism, cell cycle, and oxidative stress pathways. GSVA demonstrated significant differences in oxidative stress, inflammatory response, and lipid metabolism between obese and normal-weight children. Correlation analysis further conformed BPA's impact on metabolic-immune pathways through core genes modulation. Our findings suggest that BPA exposure may drive childhood obesity by disrupting metabolic, inflammatory, and oxidative stress pathways. The identified core genes and pathways provide a molecular basis for further research and potential therapeutic targets in BPA-related metabolic disorders.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":1.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of <i>Cymbopogon citratus</i> (lemongrass) leaf extract: phytochemical screening, antimicrobial activities, cytotoxicity, antioxidant properties, and toxicological assessment.","authors":"Samuel Gadzama Ishaya, Ndah Khan, Ali B M Ali, Great Iruoghene Edo, Alice Njolke Mafe, Emad Yousif, Endurance Fegor Isoje, Ufuoma Augustina Igbuku, Shams A Ismael, Raghda S Makia, Arthur Efeoghene Athan Essaghah, Dina S Ahmed, Huzaifa Umar","doi":"10.1080/01480545.2025.2543418","DOIUrl":"https://doi.org/10.1080/01480545.2025.2543418","url":null,"abstract":"<p><p>This study evaluates the phytochemical composition, antimicrobial activity, cytotoxicity, antioxidant potential, and toxicity profile of <i>Cymbopogon citratus</i> (lemongrass) leaf extract. The extract demonstrated antimicrobial activity with inhibition zones ranging from 14.33 ± 0.67 mm to 30.67 ± 0.88 mm for concentrations of 25-200 mg/mL against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Aspergillus niger</i>, while <i>Salmonella</i> Typhi and <i>Pseudomonas aeruginosa</i> were resistant. Minimum inhibitory concentration (MIC) values were 50 mg/mL for <i>E. coli</i> and <i>S. aureus</i>, and 25 mg/mL for <i>A. niger</i>. Cytotoxicity testing in <i>Drosophila melanogaster</i> showed low toxicity, with an LC₅₀ of 1050 mg/10 g diet. Antioxidant assays revealed significant reductions in malondialdehyde (MDA) levels and increased glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and thiol levels (<i>p</i> < 0.05). Acute toxicity testing in Swiss albino rats at 5000 mg/kg showed no mortality. Sub-chronic toxicity testing (28 days, 250-1000 mg/kg) revealed no significant changes in body or organ weights; however, elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels at 250 mg/kg indicated mild hepatotoxicity. Kidney function parameters remained stable, and hematological analysis showed enhanced erythropoiesis and immune function. These results confirm the therapeutic potential of <i>C. citratus</i> but underscore the importance of dose control to prevent hepatotoxic effects, as indicated by elevated ALT and AST levels. Limitations in advanced phytochemical profiling and histopathological validation highlight the need for future studies to refine clinical applications.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":1.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subchronic oral administration of Tamoxifen in hormonally intact female rats induces dose-dependent maladaptive behavioral phenotypes.","authors":"Isabella P Klann, Bruna C W Fulco, Cristina W Nogueira","doi":"10.1080/01480545.2025.2525146","DOIUrl":"https://doi.org/10.1080/01480545.2025.2525146","url":null,"abstract":"<p><p>Tamoxifen (TAM), the gold standard treatment for hormone-responsive breast cancer, is the most widely used Selective Estrogen Receptor Modulator (SERM). Based on the premise that subchronic oral administration of TAM may induce neurotoxic effects, we hypothesize that TAM triggers maladaptive behavior in intact female Wistar rats. The contribution of hippocampal apoptosis, inflammation, and of the hypothalamic-pituitary-adrenal (HPA) axis parameters to the maladaptive behavior was also investigated. Intact female rats (60-day-old) were treated intragastrically with TAM (0.25 and 2.5 mg/kg) for 59 days. Behavioral tests were conducted from day 120 to 125, after which the rats were euthanized. Different phenotypic manifestations of maladaptive behavior were observed in female rats treated with TAM. Psychomotor agitation and anxiety-like behavior appeared only in those receiving the lowest TAM dose. In contrast, anhedonia was observed only in female rats treated with the highest TAM dose. Behaviors, such as despair, apathy, and thigmotaxis were observed in female rats treated with both TAM doses. In <i>ex vivo</i> analysis, inflammatory markers in hippocampus of hormonally intact female rats were found to vary depending on the TAM dose. While the relative weight of the uterus decreased in TAM-exposed rats, only the highest TAM dose increased plasma corticosterone and hippocampal glucocorticoid receptor levels. Only the lowest TAM dose increased hippocampal p75NTR and Bax levels and decreased Bcl2, apoptosis markers. Summarizing, TAM subchronic oral administration, dependent on the dose, induced maladaptive behavior in intact female rats, which were associated with the hippocampal modulation of apoptosis, HPA axis markers, and inflammation.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":1.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dive into the new psychoactive substances: a review of the use of zebrafish (<i>Danio rerio</i>) as an <i>in vivo</i> model.","authors":"Leonardo Costalonga Rodrigues, Náthaly Cristine Bueno Faria Dos Santos, Isadora Locilento Denkena, Tássia Flávia Dias Castro, Eduardo Geraldo de Campos, Claudia Vianna Maurer-Morelli, Jose Luiz Costa","doi":"10.1080/01480545.2025.2548873","DOIUrl":"https://doi.org/10.1080/01480545.2025.2548873","url":null,"abstract":"<p><p>New psychoactive substances (NPS) are a broad category of drugs that pose public health risks and have poorly characterized pharmacological properties. Further studies are critical for risk assessment, toxicological profiling, and intoxication management. Human evaluations are limited by ethical and safety constraints, making animal models essential. Among <i>in vivo</i> models, zebrafish (<i>Danio rerio</i>) deserves emphasis in the study of NPS due to neurobehavioral, metabolic, and toxicological alterations. Considering some advantages, such as high genetic and neurochemical homology to humans, small body size, external fertilization, and embryo-larval transparency, zebrafish is well-suited for high-throughput screening of NPS. Their central nervous system shares key neurotransmitter pathways with mammals, supporting neurobehavioral assays. Also, a conserved cytochrome P450 system allows metabolism studies. Zebrafish have been successfully used to investigate NPS effects, with embryo-larval models offering practical advantages for acute toxicity and high-throughput behavioral screening. Adults, in turn, are more appropriate for complex behaviors and long-term or chronic exposure protocols. This review synthesizes for the first time behavior, toxicology, and metabolism data from zebrafish studies with a range of NPS classes within a unifying framework, to deliver a comprehensive understanding of their <i>in vivo</i> activity. By focusing on the translational value of zebrafish research, this review bridges experimental toxicology and clinical and forensic applications, thus filling a significant gap in current knowledge and demonstrating how zebrafish models can uniquely accelerate NPS toxicity profiling by providing mechanistic and behavioral information with high translational value.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-29"},"PeriodicalIF":1.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}