Journal of Applied Toxicology最新文献

{"title":"Pathophysiological Effects of the North Africa's Dangerous Scorpions and Antivenom Neutralization Efficacity: Unveiling the Spleen's Response.","authors":"Bouchra Darkaoui, Ayoub Lafnoune, Imane Nait Irahal, Salma Chakir, Hinde Aassila, Mohamed Aksim, Ouafaa Aniq Filali, Naoual Oukkache","doi":"10.1002/jat.4941","DOIUrl":"https://doi.org/10.1002/jat.4941","url":null,"abstract":"<p><p>The scorpion envenomations represent a serious public health issue, especially in North Africa. Their venom is known as a poison causing fatal complications. However, antivenom is the effective therapeutic approach available, showing a wide distribution in tissue compartments. Despite large-scale studies on the pathogenesis of scorpion envenomations, the spleen remains an organ not fully highlighted, even its major implication on the organism's immune response. In order to have a full view on this point, the focus will be directed for the first time towards the neutralization effects of a rabbit-made antivenom on the spleen level against the North Africa's dangerous scorpions: Androctonus australis hector (Aah), Androctonus mauretanicus (Am), and Buthus occitanus (Bo) by the direct or cross-reactivity reaction. Firstly, the acute toxicity was assessed by determining the Median Lethal Dose (LD₅₀) and Sublethal Dose (sLD), then the electrophoretic profile was generated. The Median Effective Dose 50% (ED₅₀) was conducted against each venom before proceeding to the histological examination in mouse splenic tissue, with and without administration of scorpion antivenom. Our results revealed that the spleen histo-structure was highly damaged by the toxic effect of Am, followed by Aah and Bo. Insightfully, the antivenom administered even 2 h later was able to essentially neutralize congestion and the presence of giant cells, as well as a significant reduction in red pulp hyperplasia and hemorrhagic foci. Based on these findings, the antivenom showed important effects against another vital organ highly targeted by the scorpion venoms, in view of adopting immunotherapy, especially in Morocco.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191659","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":"Cytogenotoxic and Molecular Interaction Profile of Iohexol in SH-SY5Y Human Neuroblastoma Cells: An In Vitro and In Silico Approach.","authors":"Mehmet Tahir Husunet","doi":"10.1002/jat.4945","DOIUrl":"https://doi.org/10.1002/jat.4945","url":null,"abstract":"<p><p>Iohexol, a nonionic and low-osmolality iodinated contrast agent, is widely used in medical imaging applications. Although it is generally considered safe, its potential cytotoxic and genotoxic effects on neuronal cells have not been sufficiently elucidated. In this study, the cytotoxic, genotoxic, and oxidative stress-related effects of iohexol on the SH-SY5Y human neuroblastoma cell line were evaluated by both in vitro and in silico approaches. SH-SY5Y neuroblastoma cells were exposed to increasing concentrations of iohexol in the range of 1.5-150 mg I/mL for 24 h. Cell viability was evaluated by the CCK-8 (Cell Counting Kit-8) method, and DNA damage was analyzed by alkaline comet assay. Morphological changes were examined by phase contrast microscopy. In addition, possible interactions of the iohexol molecule with double-stranded DNA (B-DNA) and the human thioredoxin reductase I (TrxR1) enzyme were investigated by molecular docking analyses. Iohexol significantly decreased cell viability with increasing concentrations; especially significant cytotoxicity was detected at concentrations ≥ 75 mg I/mL. Morphological analyses revealed cellular stress indicators such as cell rounding, shrinkage, and detachment from the surface. The comet assay revealed a mild but significant genotoxic potential at high concentrations (75 and 150 mg I/mL), indicated by an increased frequency of cells with DNA damage (Damaged Cell Index), but not in the overall severity of DNA damage (Genetic Damage Index). Molecular docking results revealed that iohexol showed weak binding affinity with B-DNA (-3.9 kcal/mol) but a moderate interaction potential with the TrxR1 enzyme (-5.99 kcal/mol). This suggests that the observed toxicity may be mediated through indirect mechanisms, such as oxidative stress, rather than direct DNA interaction. In conclusion, this study demonstrates that high concentrations of iohexol induce both cytotoxic and mild genotoxic effects in a neuronal cell model. The findings suggest that the safety profile of this contrast agent should be carefully evaluated, highlighting the importance of dose adjustment in clinical applications.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191600","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":"Anti-Inflammatory Activity of Novel Dehydrozingerone-6 (DHZ-6) Through Modulation of iNOS, COX-2, and NF-κB/p65 in LPS-Stimulated Macrophages and In Vivo Acute Lung Injury Murine Model.","authors":"Narendra Chauhan, Irfan Qasam, Avani Purohit, Shah Nawaz, Chetan Kumar, Govind Yadav","doi":"10.1002/jat.4943","DOIUrl":"https://doi.org/10.1002/jat.4943","url":null,"abstract":"<p><p>Acute lung injury (ALI) poses a significant threat in respiratory diseases and can lead to organ failure in chronic conditions. In this study, we evaluated the preventive effects of Dehydrozingerone-6 against Lipopolysaccharide (LPS)-induced inflammation in macrophages using RAW 264.7 and in a mouse model of ALI. During preliminary screening, Dehydrozingerone-6 demonstrated significant inhibition of cytokines and maintained 97% cell viability at 10 μM. Further in vitro studies showed that Dehydrozingerone-6 effectively suppressed LPS-induced production of nitric oxide, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1β), and reactive oxygen species (ROS) at a concentration of 10 μM. Immunocytochemistry and Western blot analyses revealed reduced expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nuclear Factor kappa B (NF-κB/p65), and phosphorylated IκBα (p-IκBα). In vivo LPS-induced lung injury model revealed that Dehydrozingerone-6 protected lung tissue from degradation and significantly inhibited IL-6 and TNF-α production at a dose of 50 mg/kg. Furthermore, Dehydrozingerone-6 significantly reduced carrageenan-induced paw edema and leukocyte migration. Dehydrozingerone-6 also markedly reduced vascular permeability in an acetic acid-induced model. Toxicological studies conducted at doses up to 2000 mg/kg body weight showed no notable alterations in hematological parameters or histopathology of the liver and kidney, suggesting a favorable safety profile. Overall, Dehydrozingerone-6 exhibited strong anti-inflammatory activity in vitro as well as in vivo studies by downregulating the generation of pro-inflammatory mediators and oxidative stress through attenuation of iNOS, COX-2, and NF-κB/p65.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191583","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":"Alteration of Antioxidant and Xenobiotic Metabolizing Enzyme Activities in Rainbow Trout (Oncorhynchus mykiss) Treated With Caffeine and Cotinine During the Spawning Season.","authors":"Azra Bozcaarmutlu-Büken, Akam Dler Latif Latif, Darya Shorsh Hamad Bokir, Canan Sapmaz, Hakan Türker","doi":"10.1002/jat.4936","DOIUrl":"https://doi.org/10.1002/jat.4936","url":null,"abstract":"<p><p>Caffeine and cotinine are two chemicals commonly found in aquatic environments. However, their effects on aquatic organisms during the spawning season have not been well studied. The aim of this study was to determine the effects of individual and combined exposure to caffeine and cotinine on the activities of enzymes involved in the detoxification reactions of chemicals in the liver tissues of male and female rainbow trout (Oncorhynchus mykiss) during the spawning season. For this purpose, 48 fish were exposed to 50 μg/L of caffeine, 50 μg/L of cotinine, or their combination for 48 h. The 7-ethoxyresorufin O-deethylase activity in the female caffeine administration group was significantly different from that in the female control group. The 7-pentoxyresorufin O-depentylase activity in the female cotinine administration group was significantly different from that in the female control group. Glutathione peroxidase activity in the male cotinine administration group differed significantly from that in the male control group. Glutathione S-transferase activities in the male cotinine administration and co-administration groups were significantly different from that in the male control group. It is clear that exposure to caffeine and cotinine during the spawning season alters the antioxidant and xenobiotic metabolizing enzyme activities in fish. There are gender differences in these alterations. As these enzymes are critical for the detoxification of various molecules, exposure to caffeine, cotinine, or both may influence the response of fish to other contaminants during the spawning season.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175657","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":"Comparative Analysis of Bisphenol A and Its Derivatives (BPF and BPS) on Oxidative Injury and Apoptosis in Dermal Fibroblasts.","authors":"Funda Keteci, Buket Bakan","doi":"10.1002/jat.4931","DOIUrl":"https://doi.org/10.1002/jat.4931","url":null,"abstract":"<p><p>This study provides the first comparative evaluation of Bisphenol A (BPA) and its derivatives, Bisphenol F (BPF) and Bisphenol S (BPS), with oxidative stress, lipid accumulation, and apoptosis levels in fibroblast cells. WST-1 and LDH assays revealed that while all compounds induced dose-dependent cytotoxic effects, BPA resulted in a more significant decrease in cellular viability compared with BPF and BPS. In addition, BPA demonstrated a more significant dose-dependent elevation in DCF fluorescence intensity, indicating a greater level of oxidative damage compared with BPF and BPS. Flow cytometry analyses showed that all bisphenols led to a decrease in cell viability in a dose-dependent manner, which correlated with an increase in the apoptosis and necrosis rate. All exposure groups of BPA, BPF, and BPS were determined to have diminished sizes and a more crescent nuclei morphology. Malondialdehyde (MDA) levels in the BPA group were significantly higher than in the BPF and BPS groups. The lipid droplets were markedly higher in the BPA group when compared with the BPF and BPS groups, indicating that the accumulation of neutral lipids was greater in BPA-treated fibroblast cells. These results uncover that both BPA and its analogues cause cellular toxicity, but their toxicity levels can vary. Accordingly, further studies are needed to elucidate further risk assessment categories.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175642","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":"Practical Framework for the Derivation of Health-Based Acute Exposure Guidance Values for Chemical Emergency Responses, Planning, and Prevention Programs.","authors":"Lars Hareng, Dominik Geiger, Benjamin Spielmann, Colin Ehnes, Frank Faulhammer, Melanie Flach, Wera Hubele, Lisa Andrea Kromm, Isabel Krug, Birthe Lauer, Olga Lemke, Elif Unterberger-Henig, Stefanie Welz, Edgar Leibold","doi":"10.1002/jat.4937","DOIUrl":"https://doi.org/10.1002/jat.4937","url":null,"abstract":"<p><p>Tragic accidents in chemical manufacturing plants in the last century raised the need for regulatory frameworks to control hazards, prevent or reduce the risk of major accidents and to limit the consequences for human health and the environment. The derivation of health-based Acute Exposure Guidance Values (AEGVs) is pivotal for providing science/health-based landmarks, contributing to land-use planning, industrial plant design, and the development of chemical emergency response plans. Here, we describe a pragmatic procedure to derive reliable health-based values to comply with the provisions of the Directive 2012/18/EU (Seveso Directive III). The candidate substances selection considers their hazard classification, and existing AEGVs are used in a hierarchical proceeding. If needed, company-specific Acute Exposure Threshold Level-2 (AETL-2) values, preventing irreversible health effects or escape impairment, and AETL-3 values, preventing life-threatening effects or death, are derived based on the ACUTe EXposure project methodology. Since a substantial number of substances do not possess suitable experimental inhalation toxicity data, AEGV-related information of approximately 650 substances was extracted to derive generic AEGVs based on their classification for local corrosive or irritative effects. The values obtained support that a less severe classification category translates into higher AEGVs, and local corrosive toxicity appears to be a relevant driver for the AEGV derivation. In the absence of high acute toxicity, carcinogenic, mutagenic, or reproductive toxicity (CMR) properties, or organ-specific toxicity, generic AEGVs are useful to strengthen decisions for suitable points of departure in a weight of evidence approach and to confirm the plausibility of derived AETL values.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137403","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":"Development of an Endpoint-Specific Fingerprint to Identify Structurally Similar Chemicals for Skin Sensitization Assessment by Read-Across.","authors":"Sho Suzuki, Hideyuki Mizumachi, Yuichi Ito","doi":"10.1002/jat.4934","DOIUrl":"https://doi.org/10.1002/jat.4934","url":null,"abstract":"<p><p>Human health risk assessment of cosmetic ingredients must address skin sensitization due to their direct skin application. With the recent shift toward Next Generation Risk Assessment (NGRA), which utilizes animal-free alternative testing methods, the read-across (RAx) approach has gained prominence. RAx relies on information from structural analogues to fill data gaps and determine a point of departure (PoD). A major challenge in RAx is assessing \"similarity\" between the target chemical and its analogues, typically based on chemical structure, physicochemical properties, metabolic reactivity, in silico prediction profile, and biological activity. Structural similarity, often evaluated using the Tanimoto coefficient (Tc), is a common first step, and it relies on fingerprints that convert chemical structures into machine-readable formats. However, fingerprint choice significantly influences Tc calculations and subsequent analogue selection. Moreover, no guidelines exist for the use of specific fingerprints, and which fingerprint is most suitable for skin sensitization assessment by RAx has not yet been established. This study aimed to develop a novel fingerprint specifically optimized for skin sensitization assessment. A large dataset of chemicals with the murine local lymph node assay (LLNA)-positive data was used for performance evaluation of various fingerprints. Our findings revealed that a novel fingerprint incorporating Protein Binding Alert-based Fingerprint (PBAF) and Klekota-Roth fingerprint (KRFP) features into ToxPrint outperformed others in separating suitable from unsuitable chemical pairs for RAx. This study underscores the importance of endpoint-specific fingerprint development to improve analogue selection for skin sensitization risk assessments.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131016","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":"An In Vitro and In Vivo Assessment of the Genotoxic Potential of Maizinol (UP165), a Zea mays Leaf Extract.","authors":"J Kyle Weston, Barry S Lynch, James A Akingbasote","doi":"10.1002/jat.4886","DOIUrl":"https://doi.org/10.1002/jat.4886","url":null,"abstract":"<p><p>Benzoxazinoids are secondary metabolites produced in monocotyledons and some dicotyledons from the Acanthaceae, Ranunculaceae, Scrophulariaceae, Plantaginaceae, and Lamiaceae families. Benzoxazinoids are commonly consumed in bread and cereal products that have been ingested for decades, which supports the safe use of benzoxazinoids as food ingredients. Powdered corn leaf extract (UP165), trade name Maizinol, containing 0.2%-0.3% w/w benzoxazinoid 6-methoxy-2-benzoxazolinone (6-MBOA), was the subject of genetic toxicity studies conducted according to Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG). The toxicity tests evaluated the safety of corn leaf extract (as Maizinol containing 0.2%-0.3% 6-MBOA) using a bacterial reverse mutation assay (OECD Test Guideline 471) at doses of 313, 625, 1250, 2500, or 5000 μg/plate; in vitro mammalian chromosomal aberration test (OECD TG 473) at concentrations of 9.77, 19.5, 39.1, or 78.1 μg/mL; and in vivo mammalian erythrocyte micronucleus test (OECD TG 474) at a dose of 750, 1500, or 3000 mg/kg body weight/day. Results demonstrate that Maizinol (UP165), at maximum test concentrations of 5000 μg/plate in the bacterial mutagenicity study, 78.1 μg/mL in the mammalian chromosomal aberration test, and a dose of 3000 mg/kg body weight in the rat micronucleus test, did not elicit genotoxic or mutagenic effects under the reported test conditions.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130981","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":"An Evaluation of Oral Subchronic Toxicity of Maizinol (UP165), a Zea mays Leaf Extract.","authors":"J Kyle Weston, Barry S Lynch, James A Akingbasote","doi":"10.1002/jat.4882","DOIUrl":"https://doi.org/10.1002/jat.4882","url":null,"abstract":"<p><p>Maize (Zea mays) has been consumed by humans for millennia and represents the third most abundant crop grown globally. Maize and maize-derived products have a long history of safe consumption from bread and other cereal products in human diets worldwide. Aside from key dietary components like carbohydrates and proteins, the corn plant contains endogenous biomolecules like benzoxazinoids. Benzoxazinoids are a group of secondary metabolites produced in monocotyledons and some species of dicotyledons from the Acanthaceae, Ranunculaceae, Scrophulariaceae, Plantaginaceae, and Lamiaceae families, and benzoxazinoids play a vital role in plant physiology. The current research aims to evaluate the safety of Maizinol (UP165), an ethanolic corn leaf extract containing 0.2%-0.3% of the benzoxazinoid, benzoxazolinone 6-methoxy-2-benzoxazolinone (6-MBOA) in Sprague Dawley rats. Animals were orally dosed with 0-, 750-, 1500-, or 3000-mg Maizinol/kg body weight/day for 90 days and observed for mortality and morbidity. Results revealed that Maizinol was well tolerated at all tested doses, as no significant effects were observed in hematological, biochemical, and histological endpoints at all doses. A subchronic 90-day toxicity no-observed-adverse-effect level for UP165 in Sprague Dawley rats was determined to be 3000 mg/kg body weight/day.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130968","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":"Effects of Hydroxychloroquine Used in Fracture Healing on Oxidative Stress and DNA Damage in Rat Tissues.","authors":"Elçin Bakır, Aysun Ökçesiz Hacıseyitoğlu, Salih Varol, Fazile Cantürk Tan, Kaan Gürbüz, Duran Topak, Ayşe Eken","doi":"10.1002/jat.4938","DOIUrl":"https://doi.org/10.1002/jat.4938","url":null,"abstract":"<p><p>Hydroxychloroquine is an aminoquinoline derivative drug widely used in the treatment of autoimmune diseases, rheumatoid arthritis, and malaria. In 2020, it was approved by the FDA for the treatment of COVID-19, despite a lack of clear evidence of efficacy/safety based solely on in vitro data. In our previous study, we demonstrated that orally administered hydroxychloroquine in rats impaired bone fracture healing, attributing this to increased oxidative stress in the blood. In this study, based on our previous results, we aimed to investigate the effects of the drug on oxidative stress and DNA damage that may develop over time in liver, kidney, and brain tissues in the same model. In the study, antioxidant enzyme activities and lipid peroxidation were measured as parameters of oxidative stress, and the Comet assay was used to determine potential DNA damage in rat tissues. While a dose-independent increase was observed in MDA levels in the liver and brain, the level of MDA in the kidney increased dose-dependently. DNA damage results were also consistent with MDA levels. Although oxidative damage due to bone fracture formation in the control groups showed a time-dependent change, it was not statistically significant. Our findings clearly demonstrate that hydroxychloroquine causes oxidative stress and DNA damage in the liver, kidney, and brain tissues of rats with bone fracture.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124719","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}