Toxicology Mechanisms and Methods最新文献

Acute oral toxicity evaluation of microencapsulated semi-purified fibrinolytic proteases using a modified OECD 423-aligned design for biotechnological applications. 微胶囊半纯化纤溶蛋白酶的急性口服毒性评价，采用改良的OECD 423对齐设计用于生物技术应用。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-08 DOI: 10.1080/15376516.2026.2666608

Ragil Saptaningtyas, Sri Rejeki, Ana Hidayati Mukaromah, Amin Samiasih, Nanik Rahmani, Maya Dian Rakhmawatie, Stalis Norma Ethica

{"title":"Acute oral toxicity evaluation of microencapsulated semi-purified fibrinolytic proteases using a modified OECD 423-aligned design for biotechnological applications.","authors":"Ragil Saptaningtyas, Sri Rejeki, Ana Hidayati Mukaromah, Amin Samiasih, Nanik Rahmani, Maya Dian Rakhmawatie, Stalis Norma Ethica","doi":"10.1080/15376516.2026.2666608","DOIUrl":"10.1080/15376516.2026.2666608","url":null,"abstract":"The present study evaluated the acute oral toxicity profile of microencapsulated semi-purified fibrinolytic proteases derived from Bacillus tequilensis HSFI-5 (Indonesian Patent Application No. S00202313485) using a modified OECD Guideline 423-aligned fixed-dose parallel design. BALB/c mice (n = 50; equal sex distribution) received single oral doses of 50, 300, 2000, or 5000 mg/kg body weight and were monitored for 14 days for clinical signs, body weight progression, hematological indices, clinical biochemistry parameters, organ weights, and gross pathological changes. No mortality or treatment-related clinical abnormalities were observed at any dose level. Body weight gain remained progressive and comparable to controls. Hematological and biochemical parameters showed no consistent dose-dependent deviations indicative of systemic inflammatory, metabolic, hepatic, or renal dysfunction. Absolute and relative organ weights, including liver and kidneys, remained within physiological ranges, and necropsy revealed no macroscopic lesions. Based on OECD decision criteria, the median lethal dose (LD50) was estimated to exceed 5000 mg/kg body weight, indicating that the formulation is not classified for acute oral toxicity under the Globally Harmonized System. Collectively, these findings indicate no evidence of acute treatment-related toxicological effects under the conditions of this study. Interpretation is limited to single-dose exposure and should be confirmed by further investigations incorporating detailed histopathological and extended toxicity assessments.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781980","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}

引用次数: 0

Tobacco-Specific Nitrosamine "4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)": Toxicological Mechanisms, Carcinogenicity, and Chemopreventive Approaches. 烟草特异性亚硝胺“4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）”：毒理学机制、致癌性和化学预防方法。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-07 DOI: 10.1080/15376516.2026.2668531

Divya Kumari, Pracheta Janmeda, Devendra Singh

{"title":"Tobacco-Specific Nitrosamine \"4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)\": Toxicological Mechanisms, Carcinogenicity, and Chemopreventive Approaches.","authors":"Divya Kumari, Pracheta Janmeda, Devendra Singh","doi":"10.1080/15376516.2026.2668531","DOIUrl":"https://doi.org/10.1080/15376516.2026.2668531","url":null,"abstract":"The tobacco-specific nitrosamine, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone has been identified as potent lung carcinogen in laboratory animals. Bioactivation of nicotine-derived nitrosamine ketone occurs via cytochrome P450-mediated hydroxylation of carbon atoms adjacent to the nitrosamino group, generating reactive methylating and pyridyloxobutylating intermediates. NNK can be metabolically reduced to NNAL, which retains carcinogenic potential and undergoes similar activation. Like NNK, NNAL also requires the metabolic activation to DNA alkylating agents. When NNAL is methyl hydroxylated, pyridinyl-hydroxy-butyl DNA adducts are formed, and methylene hydroxylation results in DNA methyl adducts. NNK's metabolic complexity leads to a variety of DNA lesions, increasing its overall carcinogenic potency. From this angle, the chemistry and genotoxic properties of many DNA adduct generated from NNK are discussed. Adducts that contribute to the genotoxic effects of NNK include the gene targeted for mutation, amounts and genetic variants of critical repair enzymes. NNK, present in modern smokeless tobacco products, plays a central role in cancer risk among users. The mechanisms by which NNK induces cancer in humans are discussed in this paper, along with the factors influencing NNK development at various phases of tobacco manufacturing.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-44"},"PeriodicalIF":2.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843226","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}

引用次数: 0

Nephroprotective role of edaravone against polystyrene nanoplastic-induced endoplasmic reticulum stress in Wistar rats. 依达拉奉对聚苯乙烯纳米塑料引起的内质网应激的肾保护作用。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-07 DOI: 10.1080/15376516.2026.2664035

Rachna Yadav, Ashok Jangra, Dinesh Dhingra, Sapana Kushwaha, Itishree Dubey, Dinesh Kumar

{"title":"Nephroprotective role of edaravone against polystyrene nanoplastic-induced endoplasmic reticulum stress in Wistar rats.","authors":"Rachna Yadav, Ashok Jangra, Dinesh Dhingra, Sapana Kushwaha, Itishree Dubey, Dinesh Kumar","doi":"10.1080/15376516.2026.2664035","DOIUrl":"10.1080/15376516.2026.2664035","url":null,"abstract":"Background: Plastics in particular nanoplastics pose the major environmental threat worldwide. Nanoplastics refers to smaller plastic components with size less than 100 nm. Previous studies indicated that plastics could accumulate in blood and various other tissues, leading to hepatotoxicity, nephrotoxicity, neurotoxicity, and reproductive toxicity. Endoplasmic Reticulum (ER) stress disrupts the functionality of ER due to various factors, leading to the accumulation of unfolded and misfolded proteins inside the ER. The current study aimed to investigate the protective effect of edaravone against nephrotoxicity induced by Polystyrene Nanoplastics (PSNPs) through ER-Stress pathway. In this study, we examined the role of ER Stress in PSNPs induced renal damage for the first time.Methods: A total of thirty-two female Wistar rats were used (n = 8), where the first group served as vehicle-control. The second group was administered with PSNPs (10-mg/kg, orally) over a duration of five weeks. The third and fourth groups received PSNPs combined with edaravone at dosages of 5-mg/kg and 10-mg/kg respectively during the period (Day 22nd-35th). After five weeks, animals were euthanized and samples were collected.Results: Compared to vehicle-control rats, PSNPs exposed rats demonstrated a significant elevation in creatinine, MDA and nitrite alongside a decrease in body weight, kidney weight and GSH concentration. PSNPs administered group showed significant abnormalities in kidney histopathology and increased protein expression levels of GRP78, CHOP and caspase-12, whereas edaravone treatment decreased renal oxidative stress, histopathological abnormalities and protein expression of GRP78, CHOP and caspase-12.Conclusion: Edaravone may serve as a therapeutic intervention for PSNPs induced nephrotoxicity.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781977","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}

引用次数: 0

Copper-based nanoparticles-associated neurotoxicity: ions or particles? 铜基纳米粒子-相关神经毒性：离子还是粒子？

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-07 DOI: 10.1080/15376516.2026.2664036

Zehra Keskin, Can Özgür Yalçın, Engin Yenilmez, Ezgi Öztaş, Mahmoud Abudayyak

{"title":"Copper-based nanoparticles-associated neurotoxicity: ions or particles?","authors":"Zehra Keskin, Can Özgür Yalçın, Engin Yenilmez, Ezgi Öztaş, Mahmoud Abudayyak","doi":"10.1080/15376516.2026.2664036","DOIUrl":"https://doi.org/10.1080/15376516.2026.2664036","url":null,"abstract":"The widespread use of engineered nanomaterials raises concerns regarding their potential toxicity to human health and the environment. Among metal oxide nanoparticles, copper-based nanoparticles (Cu-based NPs) are extensively produced and utilized due to their unique physicochemical properties. The dissolution of NPs leads to the release of ionic species, and still, there is no clear consensus on whether metal-based NPs' toxicity arises primarily from the nanoparticles themselves or from the ionic species generated through metal ion dissolution. This study systematically evaluated the cellular uptake and toxicological profiles of various Cu-based NPs (Cu, CuO, Cu2O, and CuFe2O4) in comparison to ionic copper (CuCl2) using the PC12 neuronal model. ICP-MS analysis demonstrated that cellular uptake was both dose- and particle-dependent; notably, CuO NPs yielded the highest intracellular copper accumulation. Cytotoxicity assays (MTT and NRU) revealed that all Cu-based NPs showed significantly higher toxicity than CuCl2. Furthermore, Cu-based NP exposure, particularly with Cu2O, triggered a robust oxidative stress response characterized by significant alterations in GSH, CAT, and MDA levels. This oxidative imbalance was closely associated with a marked increase in apoptosis and necrosis and substantial DNA damage. Our findings elucidate that the oxidation state and chemical formulation of copper nanoparticles significantly dictate their neurotoxic potential, with Cu2O NPs exhibiting the most pronounced geno- and cytotoxicity. These results highlight the necessity of considering nanoparticle-specific effects beyond simple ion dissolution in the safety assessment of engineered nanomaterials.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843239","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}

引用次数: 0

Cosmetic preservatives: physicochemical descriptors, mechanistic toxicity, and methodological approaches. 题目：化妆品防腐剂：物理化学描述符、机械毒性和方法学方法。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-04 DOI: 10.1080/15376516.2026.2656478

Wiktoria Omachel, Patrycja Pietruszewska, Anna Barbasz

{"title":"Cosmetic preservatives: physicochemical descriptors, mechanistic toxicity, and methodological approaches.","authors":"Wiktoria Omachel, Patrycja Pietruszewska, Anna Barbasz","doi":"10.1080/15376516.2026.2656478","DOIUrl":"10.1080/15376516.2026.2656478","url":null,"abstract":"Cosmetic preservatives are widely used to ensure microbiological stability, yet their health risk assessment requires an understanding of dermal penetration mechanisms, interactions with the skin barrier, and cellular responses. This review presents mechanistic aspects of toxicity across major preservative classes, including parabens, formaldehyde donors, benzyl alcohol and its derivatives, isothiazolinones, sorbic acid, and benzoic acid systems, integrating physicochemical descriptors with data on percutaneous penetration, stratum corneum (SC) retention, and systemic distribution. Key parameters such as log P, log D, bioconcentration factor, and molecular weight are discussed as predictors of preservative behavior within the SC and their toxicodynamic potential. Mechanisms of cytotoxicity, sensitization, and membrane disruption are examined in relation to the chemical structure and reactivity of individual compounds. Alternative preservation strategies, including bioactive substances, multifunctional agents, and self-preserving systems, are evaluated with respect to their physicochemical properties and biological activity. Broader determinants of preservative use, such as exposure patterns, regulatory pressures, and environmental considerations, are outlined to contextualize mechanistic findings within real-world applications. The conclusion highlights future research directions, including the potential of methods such as Langmuir monolayer modeling, lipidomics, and established in vitro and ex vivo systems to support more precise characterization of preservative-barrier interactions and advance predictive toxicology.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-27"},"PeriodicalIF":2.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692286","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}

引用次数: 0

Characterization of unusual Immunoassay Cross-Reactive Cannabinoid Metabolites in Canine Urine via Gas Chromatography-Mass Spectrometry. 用气相色谱-质谱法表征犬尿中不寻常的免疫测定交叉反应性大麻素代谢物。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-04 DOI: 10.1080/15376516.2026.2665315

Chris Pickard, John P Buchweitz, Andreas F Lehner

{"title":"Characterization of unusual Immunoassay Cross-Reactive Cannabinoid Metabolites in Canine Urine via Gas Chromatography-Mass Spectrometry.","authors":"Chris Pickard, John P Buchweitz, Andreas F Lehner","doi":"10.1080/15376516.2026.2665315","DOIUrl":"https://doi.org/10.1080/15376516.2026.2665315","url":null,"abstract":"Recent increases in cannabis use and dog ownership have elevated the risk of canine cannabis intoxication, prompting a need for efficient diagnostic tools. Enzyme immunoassays (EIAs) that employ monoclonal antibodies specific to 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) are commonly employed for preliminary screening and frequently return positive results in canine urine, yet these are not corroborated by gas chromatography-mass spectrometry (GC-MS), suggesting immunoassay cross-reactivity that raise concerns about false positives. The present study incorporated confirmatory GC-MS and GC-MS/MS analyses with mass spectral deconvolution to investigate EIA-positive, GC-MS-negative samples. Two novel compounds with molecular weights of 446 and 460 were identified following trimethylsilylation in the corresponding urine samples. Structural analysis suggests these compounds may be metabolic derivatives of tetrahydrocannabivarin (THCV), a cannabinoid with growing presence in consumer products (Pubchem, 2025). These compounds are structurally distinct from Δ9-THC-COOH yet exhibit EIA-reactivity. Ion fragmentation patterns, derivatization behavior, and comparison to established mass spectral libraries support the possibility of 11-hydroxylated and 9-carboxylated THCV analogs. The findings point to THCV metabolism as a plausible source of EIA-cross-reactivity in canines, raising important implications for veterinary toxicology and drug screening protocols. This study contributes crucial insights into canine cannabinoid metabolism and highlights limitations of existing immunoassays when influenced by structurally-similar analytes.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-22"},"PeriodicalIF":2.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821177","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}

引用次数: 0

Lauric acid attenuates hepatic lipid metabolism by modulating the AMPK-SREBP pathway in high-fat diet-induced obese mice. 月桂酸通过调节高脂饮食诱导的肥胖小鼠的AMPK-SREBP通路来减弱肝脏脂质代谢。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-01 Epub Date: 2026-02-23 DOI: 10.1080/15376516.2026.2631559

Chi Hau Wong, Lai Yen Fong, Tengku-Sifzizul Tengku-Muhammad, Quok Cheong Choo, Choy Hoong Chew

{"title":"Lauric acid attenuates hepatic lipid metabolism by modulating the AMPK-SREBP pathway in high-fat diet-induced obese mice.","authors":"Chi Hau Wong, Lai Yen Fong, Tengku-Sifzizul Tengku-Muhammad, Quok Cheong Choo, Choy Hoong Chew","doi":"10.1080/15376516.2026.2631559","DOIUrl":"10.1080/15376516.2026.2631559","url":null,"abstract":"Insulin resistance, characterized by a diminished cellular response to insulin signaling, is a central hallmark of metabolic disorders such as obesity and type 2 diabetes mellitus. This impaired responsiveness disrupts glucose and lipid homeostasis, leading to the progression of metabolic dysfunction. This study investigated the effects of lauric acid on lipid metabolism in male C57BL/6J mice. The mice were fed a high-fat diet for eight consecutive weeks to induce obesity, while the control group was fed a normal chow diet. Three experimental groups were co-treated with HFD and lauric acid (12 and 24 mg/kg orally), or HFD and rosiglitazone (20 mg/kg orally) for another eight consecutive weeks. Lauric acid reduced triglyceride levels while increasing HDL levels. Moreover, lauric acid upregulated hepatic expression of Apoa2, Pparg1 and Srebf2, and downregulated Hmgcr genes compared to HFD alone. Lauric acid treatment showed non-significant trends toward increased AMPK phosphorylation and decreased the total SREBP 1 and 2 protein in the liver. Histological examination revealed that lauric acid-fed mice showed similar hepatic morphology compared to the HFD control. Finally, the data suggest that lauric acid is a potential nutraceutical intervention for lipid-lowering and insulin resistance in obese individuals.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"503-514"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271989","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}

引用次数: 0

Investigation of the underlying mechanism of rifampicin-induced hepatotoxicity and neurotoxicity in mice by untargeted metabolomics and gut microbiota approach. 通过非靶向代谢组学和肠道微生物群方法研究利福平诱导小鼠肝毒性和神经毒性的潜在机制。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-01 Epub Date: 2026-02-24 DOI: 10.1080/15376516.2026.2632678

Jiuli Yuan, Lina Tao, Yanjiao Li, Wei Zhou, Xiaoyu Qu

{"title":"Investigation of the underlying mechanism of rifampicin-induced hepatotoxicity and neurotoxicity in mice by untargeted metabolomics and gut microbiota approach.","authors":"Jiuli Yuan, Lina Tao, Yanjiao Li, Wei Zhou, Xiaoyu Qu","doi":"10.1080/15376516.2026.2632678","DOIUrl":"10.1080/15376516.2026.2632678","url":null,"abstract":"Rifampicin (RIF) remains a first-line antituberculosis agent. However, its usefulness is limited by its hepatotoxicity and potential neurotoxicity. The aim of this study was to investigate the association between dysbiosis of gut microbiota and dysregulation of liver and brain metabolites in mice induced by treatment with RIF. Microbiota analysis (16S rRNA gene sequencing) using fecal samples and untargeted metabolomic analysis using liver and brain tissues were performed to investigate the mechanism in RIF-induced hepatotoxicity and neurotoxicity. A total of 32 and 27 metabolites were altered in the liver and brain of mice, respectively. Based on the gut microbiota analysis, Proteobacteria and Verrucomicrobia (at the phylum level), as well as Akkermansia, Allobaculum, and Lactobacillus (at the genus level) were markedly changed in the 240 mg/kg RIF group versus the controls. The pathway analysis indicated that energy metabolism and important nutrients metabolism were disrupted, leading to inflammatory response and oxidative stress. To our knowledge, this is the first study demonstrating an alteration of gut microbiota and metabolites in the liver and brain of mice after exposure to RIF. This evidence may provide a direction for investigating the mechanism underlying the hepatotoxicity and neurotoxicity induced by treatment with RIF.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"527-539"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285271","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}

引用次数: 0

Introducing AutoML framework for drug-drug interaction prediction: application of AutoGluon. 介绍药物相互作用预测的AutoML框架：AutoGluon的应用。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-01 Epub Date: 2026-04-13 DOI: 10.1080/15376516.2026.2628929

Abdallah Abou Hajal, Molham Sakkal

{"title":"Introducing AutoML framework for drug-drug interaction prediction: application of AutoGluon.","authors":"Abdallah Abou Hajal, Molham Sakkal","doi":"10.1080/15376516.2026.2628929","DOIUrl":"10.1080/15376516.2026.2628929","url":null,"abstract":"Drug-drug interactions (DDIs) remain a major concern in medication safety. Although advanced artificial intelligence methods such as deep learning have improved DDI prediction, their adoption is limited by the need for specialized expertise and complex model development. This study introduces the first application of the AutoGluon AutoML framework to DDI prediction using molecular features, aiming to automate and simplify model development. A curated subset of 100,000 drug pairs from DrugBank was used, employing three molecular representations: 2D molecular descriptors, 2048-bit Morgan fingerprints, and their combination. Models were trained using AutoGluon-Tabular with no manual hyperparameter tuning. The descriptor-only model achieved the best performance, with 84.4% test accuracy and an AUC of 0.916, outperforming fingerprint-based and hybrid models. Feature importance analysis identified key physicochemical and topological descriptors-such as drug-likeness, electrotopological indices, and hydrophobic surface area-as critical predictors of DDIs. These results demonstrate that AutoML can extract chemically meaningful patterns while reducing technical barriers. Overall, our results validate AutoGluon as a scalable approach to DDI prediction that provides chemically meaningful, feature-level interpretability, and lay the groundwork for future applications involving larger datasets and more complex chemical representations.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"494-502"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137456","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}

引用次数: 0

Syringic acid exhibits ameliorative effects against cyclosporine A-induced cardiotoxicity in mice by mitigating oxidative stress, inflammatory response, and apoptotic cell death. 丁香酸通过减轻氧化应激、炎症反应和凋亡细胞死亡，对环孢素a诱导的小鼠心脏毒性有改善作用。

IF 2.7 4区医学

Toxicology Mechanisms and Methods Pub Date : 2026-05-01 Epub Date: 2026-02-25 DOI: 10.1080/15376516.2026.2634121

Susan Sabbagh, Hassan Abbaszadeh, Parisa Beigi

{"title":"Syringic acid exhibits ameliorative effects against cyclosporine A-induced cardiotoxicity in mice by mitigating oxidative stress, inflammatory response, and apoptotic cell death.","authors":"Susan Sabbagh, Hassan Abbaszadeh, Parisa Beigi","doi":"10.1080/15376516.2026.2634121","DOIUrl":"10.1080/15376516.2026.2634121","url":null,"abstract":"Cyclosporine A (CsA) is a commonly used drug to inhibit graft rejection and treat a variety of autoimmune diseases. Cardiotoxicity is one of the most serious undesirable effects of CsA which has limited its clinical use. Syringic acid (SA) is a polyphenolic compound with several striking biological influences. The current study aimed to investigate the ameliorative activity of SA against CsA-induced cardiotoxicity. Forty male mice were allocated into five groups: control (normal saline) group, CsA (30 mg/kg, s.c.) group, SA (25, 50, and 100 mg/kg, i.p.) + CsA groups. Animals received the drugs for 21 days and pretreatment with SA was carried out one hour prior to CsA injection. Results demonstrated that CsA remarkably enhanced the activities of AST, CK-MB, and LDH as well as the serum level of troponin I. CsA triggered oxidative stress by elevating the levels of cardiac oxidants, MDA and NO and reducing the activities of cardiac antioxidants, SOD and GPx. Furthermore, CsA significantly increased the protein expression of cardiac pro-inflammatory cytokines, TNF-α and IL-1β. CsA markedly provoked cardiac apoptosis by upregulating the protein expression of Bax and cleaved caspase-3 and downregulating the protein expression of Bcl-2. The histopathological evaluations validated the above-mentioned findings. However, all these alterations were considerably mitigated in SA-treated mice. These data highlight the fundamental role of oxidative stress, inflammation, and apoptosis in CsA-mediated cardiotoxicity that significantly suppressed by administration of SA. Therefore, SA can act as a promising cardioprotective agent to effectively prevent CsA-induced cardiac injury.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"540-551"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310592","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}

引用次数: 0