Current Research in Toxicology最新文献

{"title":"Fit for purpose testing and independent GMP validation of the monocyte activation test","authors":"Ruth Daniels ,&nbsp;Wim Van der Elst ,&nbsp;Chi K. So ,&nbsp;Liesbeth Voeten ,&nbsp;Philip Breugelmans ,&nbsp;Marijke W.A. Molenaar-de Backer ,&nbsp;Stephen Poole ,&nbsp;Mehul Patel","doi":"10.1016/j.crtox.2024.100206","DOIUrl":"10.1016/j.crtox.2024.100206","url":null,"abstract":"<div><div>The present study describes the “fit for purpose” testing and the independent product-specific GMP validation of the monocyte activation test (MAT) to detect pyrogenic and pro-inflammatory contaminants, MAT Method A, Quantitative Test (<span><span>European Pharmacopoeia, Ph. Eur. chapter 2.6.30, 2017</span></span>). A fit for purpose study was carried out to ensure that the chosen MAT set-up (cryopreserved PBMC, IL-6 detection) can reliably discriminate between batches of product containing pyrogenic contaminants below the contaminants limit concentration, CLC, from batches containing pyrogenic contaminants above the CLC. Such testing is carried out once, before the chosen MAT set-up is used for subsequent product testing to show that the incidence of false positives (pyrogen-negative (&lt;CLC) batches testing as pyrogen-positive (&gt;CLC) batches) and – especially – false negatives (pyrogen-positive (&gt;CLC) testing as pyrogen-negative (&lt;CLC)) is low. This study also afforded the opportunity to collect an independent body of validation data for comparison with that obtained previously (<span><span>Daniels et al., 2022</span></span>) to evaluate the robustness of MAT Method A and its fitness to replace the rabbit pyrogen test (RPT) where this has not already happened.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100206"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970094","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":"Evaluation of the impact of a 8 week exposure to a portable light therapy device, Luminette®, on retinal function assessed by ElectroRetinoGraphy","authors":"Marie de Deus ,&nbsp;Charlotte Petit ,&nbsp;Eve Cosker ,&nbsp;Amandine Luc ,&nbsp;Cédric Baumann ,&nbsp;Thomas Schwitzer","doi":"10.1016/j.crtox.2025.100253","DOIUrl":"10.1016/j.crtox.2025.100253","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) treatment can be long and difficult to obtain. Thus, alternative non-pharmacological treatments, such as light therapy (LT), are increasingly recommended to treat MDD. For better treatment adherence, portable LT devices have been developed. However, more research is needed to better understand their safety of their use on patients’ physiology. One way to explore it is evaluating the retina function. That is why the aim of the study presented was to assess, thanks to Electroretinography (ERG), the impact on retinal function of an 8 weeks exposure to an active or a placebo LT portable device in MDD patients.</div></div><div><h3>Method</h3><div>MDD patients were treated with an active portable LT device or with a placebo LT device. The LT device tested was Luminette®. ERG measurements were carried out before the start of the LT treatment and 4 and 8 weeks afterwards.</div></div><div><h3>Results</h3><div>No significant differences were found in the ERG waveforms between the patients treated with active Luminette® and patients treated with the placebo device.</div></div><div><h3>Conclusions</h3><div>The use of the Luminette® device for 8 weeks, combined with usual care, did not result in any morphological or quantitative alterations in ERG waveforms in our cohort of MDD patients. This portable LT device would therefore be well tolerated at retinal level in MDD patients.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"9 ","pages":"Article 100253"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of mineral fibres in an in vitro placental syncytiotrophoblast model","authors":"Giovanni Tossetta ,&nbsp;Sonia Fantone ,&nbsp;Antonio Domenico Procopio ,&nbsp;Armanda Pugnaloni ,&nbsp;Alessandro Francesco Gualtieri ,&nbsp;Daniela Marzioni","doi":"10.1016/j.crtox.2025.100231","DOIUrl":"10.1016/j.crtox.2025.100231","url":null,"abstract":"<div><div>It is known that mineral fibres can be found in placental tissues, but their effect is not known on these tissues. BeWo in vitro model of syncytiotrophoblast, the outer layer of maternal-foetal barrier, is necessary to understand if mineral fibres can alter placental cell turnover and consequently to influence the outcome of pregnancy. We performed in vitro experiments using chrysotile UICC (UICC), chrysotile Valmalenco (VM) and erionite (ERI) to investigate the potential cytotoxic effects of these mineral fibres on BeWo cells. We demonstrated that all fibres are toxic while only UICC fibres caused a DNA damage that the cells were not able to repair through RAD51 activity. In addition, we demonstrated that DNA replication is not altered while cyclin D1 showed a significant decrease in VM and UICC suggesting that the cell cycle is altered in G1 phase. Moreover, UICC increased active form of caspase 3 demonstrating that apoptosis can be induced in BeWo cells. We suggest that although morphological changes are not visible in BeWo cells treated with these mineral fibres, DNA damage can lead to altered placenta physiology that can be seen late when the damage at the foetal tissues has already occurred.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100231"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747765","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":"Evaluation of a hypothesized Sertoli cell-based adverse outcome pathway for effects of diisononyl phthalate on the developing testis","authors":"J.M. Rogers ,&nbsp;A.N. Buerger ,&nbsp;M.M. Heintz ,&nbsp;C.M. Palermo ,&nbsp;L.C. Haws ,&nbsp;I.A. Lea","doi":"10.1016/j.crtox.2025.100219","DOIUrl":"10.1016/j.crtox.2025.100219","url":null,"abstract":"<div><div>Exposure of pregnant rats to some phthalates during the masculinization programming window (MPW) can lower fetal testis testosterone production and adversely affect development of the fetal male reproductive tract. Some of the effects in rats are androgen-dependent, while others also occur in mice without lower testosterone production. An adverse outcome pathway (AOP) network has been proposed for these developmental effects that includes both androgen-dependent and androgen-independent pathways, the latter of which includes a short list of putative molecular initiating events (MIEs) including peroxisome proliferator activated receptor (PPAR) activation, and effects on Sertoli cells in the developing testes as early key events (KEs) (PMID 34314370). Data from peer-reviewed literature, publicly cited toxicology reports, and EPA’s Toxicity Forecaster (ToxCast) were evaluated in the context of this hypothesized Sertoli cell-based AOP and exposure to diisononyl phthalate (DINP). Each of the fifteen identified studies underwent a risk of bias (RoB) assessment, which revealed a high risk of bias for all but one study endpoint. <em>In vitro</em> evidence in kidney, liver, and fibroblast-like cell lines indicates that the DINP metabolites mono-isononyl phthalate (MINP) and mono-hydroxyisononyl phthalate (MHINP) activate PPARα/γ and that mouse PPARα/γ are more sensitive than human PPARα/γ. However, DINP did not activate PPARα-related genes in rat fetal testes at high maternal dosages (PMID 22112501), and it remains unknown whether PPARs are expressed in fetal Sertoli cells. Overall, there is insufficient evidence to evaluate whether PPAR activation in the developing male reproductive tract is causally linked to the KEs in the hypothesized AOP. Regarding the KEs, no <em>in vivo</em> studies were identified that examined the effects of DINP on Sertoli cell proliferation or cytoskeleton; a single <em>in vitro</em> study found no effect of DINP on Sertoli cell proliferation. There was limited and conflicting evidence for the effects of DINP on tubulogenesis, but strong <em>in vivo</em> evidence for increased multinucleated germ (MNG) cells. No evidence was found concerning germ cell apoptosis. For the adverse outcomes (AOs), there was limited <em>in vivo</em> evidence for testicular dysgenesis following altered tubulogenesis, and impaired spermatogenesis following increased MNGs. There was strong evidence against reduced fertility, but this is not a sensitive endpoint in rats given their robust sperm production and excess capacity. In conclusion, following <em>in utero</em> DINP exposure, while PPAR activation (MIE) is plausible, linkage to effects on Sertoli cells and downstream AOPs is lacking. The sparse evidence currently available is insufficient to support the applicability of the hypothesized Sertoli cell-based AOP to DINP.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100219"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563253","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":"A Review of the Applications, Benefits, and Challenges of Generative AI for Sustainable Toxicology","authors":"Furqan Alam ,&nbsp;Tahani Saleh Mohammed Alnazzawi ,&nbsp;Rashid Mehmood ,&nbsp;Ahmed Al-maghthawi","doi":"10.1016/j.crtox.2025.100232","DOIUrl":"10.1016/j.crtox.2025.100232","url":null,"abstract":"<div><div>Sustainable toxicology is vital for living species and the environment because it guarantees the safety, efficacy, and regulatory compliance of drugs, treatments, vaccines, and chemicals in living organisms and the environment. Conventional toxicological methods often lack sustainability as they are costly, time-consuming, and sometimes inaccurate. It means delays in producing new drugs, vaccines, and treatments and understanding the adverse effects of the chemicals on the environment. To address these challenges, the healthcare sector must leverage the power of the Generative-AI (GenAI) paradigm. This paper aims to help understand how the healthcare field can be revolutionized in multiple ways by using GenAI to facilitate sustainable toxicological developments. This paper first reviews the present literature and identifies the possible classes of GenAI that can be applied to toxicology. A generalized and holistic visualization of various toxicological processes powered by GenAI is presented in tandem. The paper discussed toxicological risk assessment and management, spotlighting how global agencies and organizations are forming policies to standardize and regulate AI-related development, such as GenAI, in these fields. The paper identifies and discusses the advantages and challenges of GenAI in toxicology. Further, the paper outlines how GenAI empowers Conversational-AI, which will be critical for highly tailored toxicological solutions. This review will help to develop a comprehensive understanding of the impacts and future potential of GenAI in the field of toxicology. The knowledge gained can be applied to create sustainable GenAI applications for various problems in toxicology, ultimately benefiting our societies and the environment.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100232"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting seizure liability of small molecules using an in vitro multi-electrode array based assay coupled with modeling of brain disposition","authors":"David G. Belair ,&nbsp;Rebecca Kohnken ,&nbsp;Rebecca L. McCloud ,&nbsp;Stephanie Sandoval ,&nbsp;Jonathon Green ,&nbsp;Wayne R. Buck ,&nbsp;James S. Polakowski","doi":"10.1016/j.crtox.2025.100236","DOIUrl":"10.1016/j.crtox.2025.100236","url":null,"abstract":"<div><div>Unintended central nervous system (CNS) effects of small molecule drugs can lead to costly attrition during drug development. CNS liability can be assessed with biochemical assays, as part of routine nonclinical toxicology studies, or via a battery of rodent CNS tests. Alternative in vitro methods have been developed for assessing CNS liability of small molecule drugs though their use in drug development has lagged relative to other organ systems of interest including cardiac, hepatic, and gastrointestinal. In the present study, 13 commercially available small molecule drugs and 15 experimental AbbVie compounds were evaluated in an in vitro seizure assay consisting of human-induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons cultured on a multi-electrode array (MEA). Across all 28 compounds, the in vitro seizure assay exhibited 58% sensitivity and 78% specificity. A mathematical model of brain penetrance was used to predict brain exposures in cynomolgus monkey and improved the concordance of the in vitro seizure assay with in vivo seizure liability, highlighting that the in vitro assay together with CNS exposure prediction could serve as a useful tool for characterizing seizure liability of a small molecule drug candidate.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100236"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a workflow for in vitro on– and off-target cytotoxicity assessment of CAR T cell therapies to support first-in-human clinical trials: An orthogonal approach using human induced pluripotent stem cell-derived cells as a surrogate for normal vital organ systems","authors":"Shari Price ,&nbsp;Krista G. Zindel ,&nbsp;Joshua K. Overcash ,&nbsp;Elizabeth Glaze ,&nbsp;Sandy Eldridge","doi":"10.1016/j.crtox.2025.100243","DOIUrl":"10.1016/j.crtox.2025.100243","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer therapy and is showing promise for other non-cancer disease indications. CAR T cells are directed to a target antigen that is overexpressed by tumor cells. On-target toxicity can arise if the targeted protein is also expressed in normal cell populations. Additionally, off-target toxicity may occur if the CAR T cell recognizes or cross-reacts with a non-target protein thereby activating the T cells leading to subsequent adverse sequela. Given the nature of this biological class as a human cellular product, standard safety assessments in animals are largely not appropriate as the drug product is derived from human cells and the associated CAR often lacks reactivity with the animal homolog of the target protein. Undesired targeting of healthy/normal tissue that express the intended target antigen (on-target/off-tumor), as well as unintended targeting of other antigens expressed on healthy/normal tissue is a safety concern that may be explored using human induced pluripotent stem cell (hiPSC)-derived test systems as surrogates for various normal cell types. The panel of hiPSC-derived cells is intended to broadly represent different human cell types from vital organs that can be targets for severe adverse events. Herein the development of an orthogonal approach to an in vitro co-culture assay used to assess unintended CAR T cell cytotoxicity in normal cells is described. Experimental considerations including assay and cell model qualification are presented, and an orthogonal workflow described. Finally, an illustrative case of experimental CD33 CAR T cells co-cultured with a select panel of hiPSC-derived normal cells serves as a springboard for other CAR T cell developers to consider in their nonclinical safety programs.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100243"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics study and cytotoxicity of several curcumin analogues in ovarian cancer","authors":"Retno Murwanti ,&nbsp;Ritmaleni ,&nbsp;Navista Sri Octa Ujiantari ,&nbsp;I Made Rhamandana Putra ,&nbsp;Aliffian Farhan Wahyudi ,&nbsp;Vigha Ilmanafi Arifka","doi":"10.1016/j.crtox.2025.100230","DOIUrl":"10.1016/j.crtox.2025.100230","url":null,"abstract":"<div><div>Ovarian cancer ranks as Indonesia’s third-leading cause of cancer-related death, emphasising the need for innovative treatments. This study combined bioinformatics, molecular docking, and experimental assays to tackle this challenge. We identified 166 ovarian cancer-related genes, with MYC standing out as a key target. Analysis of MYC mutations revealed prevalent alterations, though no significant survival differences were observed in patients with or without the mutations. Molecular docking pinpointed compound B155 as a promising MYC inhibitor. A preliminary cytotoxicity assay revealed compound B155′s notable activity, with an 87.19 % inhibition of cell viability at 50 μM. Most of the other curcumin analogues only caused more than 50 % inhibition at the same concentration. This result suggests alternative mechanisms of action, possibly antioxidant effects, warranting further exploration. In summary, this study unveiled MYC as a prime target for ovarian cancer treatment, with curcumin analogues like B155 showing potential. Nonetheless, the complex factors affecting cytotoxicity underscore the need for deeper investigation into these compounds’ mechanisms in ovarian cancer cells.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100230"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747764","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":"Toxicological impacts and mitigation strategies of food contaminants: a global perspective and comprehensive narrative review","authors":"Gudisa Bereda","doi":"10.1016/j.crtox.2025.100268","DOIUrl":"10.1016/j.crtox.2025.100268","url":null,"abstract":"<div><div>Food contaminants—including chemical, biological, physical, allergenic, and radiological agents—pose major global food safety challenges. This review synthesizes evidence from 2014 to 2025 on Food contaminants sources, cellular and molecular mechanisms, monitoring strategies, and mitigation approaches. Major food contaminants include heavy metals (lead, mercury, cadmium, and arsenic), mycotoxins (aflatoxins, and ochratoxin A), pesticide residues, allergens, microplastics, per- and polyfluoroalkyl substances (PFAS), radioactive isotopes (cesium-137, and iodine-131), and microbial agents such as Bacillus, Salmonella, Listeria, and Escherichia species. At the molecular level, heavy metals trigger oxidative stress, mitochondrial dysfunction, and DNA damage; aflatoxins form DNA adducts, driving carcinogenesis; organophosphate residues inhibit cholinesterase; allergens activate IgE-mediated hypersensitivity; and radiological agents generate reactive oxygen species, causing lipid peroxidation and genomic instability. Regulatory agencies, including WHO, FDA, EFSA, and the European Commission, classify metals as priority hazardous substances and set maximum residue limits (MRLs), tolerable daily intakes (TDIs), and action levels for vulnerable populations, such as children. For example, cadmium in wheat is limited to 100 ppb in the EU, lead in candy to 0.1 ppm, and arsenic in apple juice to 10 ppb. Advanced detection technologies, such as liquid chromatography–mass spectrometry (LC-MS) and inductively coupled plasma mass spectrometry (ICP-MS), enable precise monitoring of contaminants at trace levels. Mitigation strategies emphasize improved agricultural practices, safe processing, allergen control, environmental monitoring, and policy enforcement. Ongoing research on emerging contaminants, particularly PFAS and nanoplastics, is crucial to strengthening food safety systems and protecting public health.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"9 ","pages":"Article 100268"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effect of targeting cisplatin-induced nitrative stress using MnTBAP in auditory and cancer cells","authors":"Shomaila Mehmood,&nbsp;Pankaj Bhatia,&nbsp;Nicole Doyon-Reale,&nbsp;Samson Jamesdaniel","doi":"10.1016/j.crtox.2025.100241","DOIUrl":"10.1016/j.crtox.2025.100241","url":null,"abstract":"<div><div>Ototoxicity is a major dose-limiting side effect of cisplatin, a highly effective anti-cancer drug used to treat many solid tumors. Oxidative stress plays a central role in mediating cisplatin-induced ototoxicity. However, broad-spectrum antioxidants that prevent ototoxicity compromise the anti-cancer activity of cisplatin. Therefore, there is a need to identify novel interventional targets/compounds for otoprotection. Recent reports indicated that cisplatin-induced nitration of cochlear proteins is a critical factor in causing ototoxicity, and inhibition of cochlear nitrative stress mitigated cisplatin-induced ototoxicity. The use of peroxynitrite decomposition catalysts that selectively target nitrative stress appears to be an attractive strategy for mitigating the ototoxic effects of cisplatin because they do not scavenge free radicals. We hypothesized that cotreatment with selective inhibitors of nitrative stress prevents cisplatin-induced ototoxicity without compromising the anti-cancer effects. Here, we test this hypothesis by investigating the effect of MnTBAP cotreatment on cell viability, nitrative stress, DNA damage, and cell migration in cisplatin-treated organ of Corti as well as cancer cells. Our results indicate that cisplatin treatment decreases cell viability in both auditory and cancer cells, while cotreatment with MnTBAP mitigates cisplatin-induced cytotoxicity in the auditory cells but not in the cancer cells. Collectively, the findings of this study suggest that selective targeting of cisplatin-induced nitrative stress is a promising strategy for mitigating the ototoxic effects of cisplatin because it does not compromise the anti-cancer effects.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100241"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}