{"title":"<i>In vitro</i> evaluation of the toxicological effects of cooking oil fumes using a self-designed microfluidic chip.","authors":"Boyang Feng, Xiang Li, Zezhi Li, Junwei Zhao, Kejian Liu, Fuwei Xie, Xiaobing Zhang","doi":"10.1080/15376516.2024.2369941","DOIUrl":"10.1080/15376516.2024.2369941","url":null,"abstract":"<p><p>Cooking oil fumes (COFs) are widely acknowledged as substantial contributors to indoor air pollution, having detrimental effects on human health. Despite the existence of commercialized <i>in vitro</i> aerosol exposure platforms, assessment risks of aerosol pollutants are primarily evaluated based on multiwell plate experiments by trapping and redissolving aerosols to conduct comprehensive <i>in vitro</i> immersion exposure manner. Therefore, an innovative real-time exposure system for COF aerosol was constructed, featuring a self-designed microfluidic chip as its focal component. The chip was used to assess toxicological effects of <i>in vitro</i> exposure to COF aerosol on cells cultured at the gas-liquid interface. Meanwhile, we used transcriptomics to analyze genes that exhibited differential expression in cells induced by COF aerosol. The findings indicated that the MAPK signaling pathway, known for its involvement in inflammatory response and oxidative stress, played a crucial role in the biological effects induced by COF aerosol. Biomarkers associated with inflammatory response and oxidative stress exhibited corresponding alterations. Furthermore, the concentration of COF aerosol exposure and post-exposure duration exert decisive effects on these biomarkers. Thus, the study suggests that COF can induce oxidative stress and inflammatory response in BEAS-2B cells, potentially exerting a discernible impact on human health.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1000-1009"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421018","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}
Nguyen Tran Nam Tien, Trinh Tam Anh, Nguyen Thi Hai Yen, Nguyen Ky Anh, Huy Truong Nguyen, Ho-Sook Kim, Jung-Hwa Oh, Dong-Hyun Kim, Nguyen Phuoc Long
{"title":"Time-course cross-species transcriptomics reveals conserved hepatotoxicity pathways induced by repeated administration of cyclosporine A.","authors":"Nguyen Tran Nam Tien, Trinh Tam Anh, Nguyen Thi Hai Yen, Nguyen Ky Anh, Huy Truong Nguyen, Ho-Sook Kim, Jung-Hwa Oh, Dong-Hyun Kim, Nguyen Phuoc Long","doi":"10.1080/15376516.2024.2371894","DOIUrl":"10.1080/15376516.2024.2371894","url":null,"abstract":"<p><p>Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. <i>TUBB2A</i>, <i>PLIN2</i>, <i>APOB</i>) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1010-1021"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470944","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}
Shahram Lotfi, Shahin Ahmadi, Ali Azimi, Parvin Kumar
{"title":"<i>In silico</i> aquatic toxicity prediction of chemicals toward <i>Daphnia magna</i> and fathead minnow using Monte Carlo approaches.","authors":"Shahram Lotfi, Shahin Ahmadi, Ali Azimi, Parvin Kumar","doi":"10.1080/15376516.2024.2416226","DOIUrl":"10.1080/15376516.2024.2416226","url":null,"abstract":"<p><p>The fast-increasing use of chemicals led to large numbers of chemical compounds entering the aquatic environment, raising concerns about their potential effects on ecosystems. Therefore, assessment of the ecotoxicological features of organic compounds on aquatic organisms is very important. <i>Daphnia magna</i> and <i>Fathead minnow</i> are two aquatic species that are commonly tested as standard test organisms for aquatic risk assessment and are typically chosen as the biological model for the ecotoxicology investigations of chemical pollutants. Herein, global quantitative structure-toxicity relationship (QSTR) models have been developed to predict the toxicity (pEC(LC)50) of a large dataset comprising 2106 chemicals toward <i>Daphnia magna</i> and <i>Fathead minnow</i>. The optimal descriptor of correlation weights (DCWs) is calculated using the notation of simplified molecular input line entry system (SMILES) and is used to construct QSTR models. Three target functions, TF<sub>1</sub>, TF<sub>2</sub>, and TF<sub>3</sub> are utilized to generate 12 QSTR models from four splits, and their statistical characteristics are also compared. The designed QSTR models are validated using both internal and external validation criteria and are found to be reliable, robust, and excellently predictive. Among the models, those generated using the TF<sub>3</sub> demonstrate the best statistical quality with <i>R</i><sup>2</sup> values ranging from 0.9467 to 0.9607, <i>Q</i><sup>2</sup> values ranging from 0.9462 to 0.9603 and RMSE values ranging from 0.3764 to 0.4413 for the validation set. The applicability domain and the mechanistic interpretations of generated models were also discussed.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475444","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}
Thiago Guedes Pinto, Thayza Aires Dias, Daniel Araki Ribeiro
{"title":"Do professional painters comprise a high risk group for genotoxicity? A systematic review.","authors":"Thiago Guedes Pinto, Thayza Aires Dias, Daniel Araki Ribeiro","doi":"10.1080/15376516.2024.2411060","DOIUrl":"https://doi.org/10.1080/15376516.2024.2411060","url":null,"abstract":"<p><p>Professional painters represent an occupational population group that deserves attention for study in the field of occupational toxicology due to the wide range of complex chemical mixtures they are exposed to. It is imperative to underscore that the International Agency for Research on Cancer has classified commercial painting as a high-risk occupation for the development of cancer. Given this context, the primary objective of the present study was to conduct a systematic review aimed at addressing the following question: are car painters at occupational risk regarding potential genotoxicity? To address this question, a selection process was undertaken, with three reviewers carefully selecting, reading, and analyzing full manuscripts from 26 studies included in this review. The technical rigor of these studies underwent meticulous scrutiny, culminating in the classification of six studies as Strong, eight as Moderate, and 12 as Weak, predicated on the extent of confounders considered. Taken together, the findings suggest that chemical substances from paints may indeed pose a risk of genotoxicity for professionals in this field, as all studies indicated genotoxicity among professional painters through various tests.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393536","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}
Thiago Guedes Pinto, Fernando Augusto Cintra Magalhães, Ana Claudia Muniz Renno, Daniel Araki Ribeiro
{"title":"Does waterpipe smoke induce genotoxicity (DNA damage) in mammalian cells <i>in vivo</i>? A systematic review.","authors":"Thiago Guedes Pinto, Fernando Augusto Cintra Magalhães, Ana Claudia Muniz Renno, Daniel Araki Ribeiro","doi":"10.1080/15376516.2024.2411381","DOIUrl":"https://doi.org/10.1080/15376516.2024.2411381","url":null,"abstract":"<p><p>The waterpipe works by placing tobacco in a bowl with holes at the bottom, which is connected to a tube leading to a water-filled container. Upon heating the tobacco product with hot charcoal placed atop it, the emanating smoke is inhaled by the user <i>via</i> a hose linked to the water receptacle. The aim of this literature review is to evaluate whether the use of waterpipes can indeed induce genotoxicity in mammalian cells <i>in vivo</i>. Additionally, the study aims to assess the quality of the included research articles on this topic to ensure the reliability of the findings. We performed comprehensive searches in PubMed, SCOPUS, and Web of Science to identify relevant articles published until July 2024. The findings confirmed that waterpipe smoke induces genetic damage. This assertion is supported by the fact that 11 studies (out of 15) received a Strong or Moderate assessment categorization, suggesting that the majority of studies adhered to most technical standards, thereby enhancing the reliability of the research findings. Regarding the types of DNA damage reported, DNA strand breaks, chromosome damage and oxidative DNA damage were found in this review. Taken together, this study holds significant importance in assessing the efficacy of genotoxicity assays in detecting DNA damage due to waterpipe smoke and the comet and micronucleus assays are suitable biomarkers for biomonitoring people who use waterpipe.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381704","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}
Asma Hamzaoui, Amal Feki, Malek Eleroui, Zakaria Boujhoud, Rim Kallel, Christian Magné, Nathalie Deschamps, Amina Nasri, Jean Marc Pujo, Hatem Kallel, Ibtissem Ben Amara
{"title":"Protective effects of polysaccharide extracted from green alga <i>Chaetomorpha linum</i> against zinc and copper-induced testicular toxicity in male mice.","authors":"Asma Hamzaoui, Amal Feki, Malek Eleroui, Zakaria Boujhoud, Rim Kallel, Christian Magné, Nathalie Deschamps, Amina Nasri, Jean Marc Pujo, Hatem Kallel, Ibtissem Ben Amara","doi":"10.1080/15376516.2024.2361070","DOIUrl":"10.1080/15376516.2024.2361070","url":null,"abstract":"<p><p>This study aimed to investigate the effects of copper (CuSO<sub>4</sub>) and zinc (ZnSO<sub>4</sub>) overload on male reproductive toxicity and the potential of a polysaccharide extracted from green alga <i>Chaetomorpha linum</i> (PS) in mitigating their toxicities. Adult male mice strain of 25 ± 2 g of weight was subdivided into eight groups. Group 1 served as control; group 2 received PS (200 mg/kg), and groups 3 and 4 received intraperitoneally zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), respectively. Group 5 received both zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), group 6 received zinc (60 mg/kg b.w) associated with PS (200 mg/kg), group 7 received copper (33 mg/kg b.w) associated with PS (200 mg/kg), and group 8 received zinc (60 mg/kg b.w) and copper (33 mg/kg b.w) associated with PS (200 mg/kg). Results suggested that ZnSO<sub>4</sub> and CuSO<sub>4</sub> significantly decreased the functional sperm parameters. Furthermore, extended exposure to these elements increased oxidative stress biomarkers, including malondialdehyde (MDA) as a measure of lipid peroxidation and advanced oxidation protein products (AOPP) indicating protein oxidative damage. This process also reduces the activity of antioxidant enzymes such as glutathione (GSH) and glutathione peroxidase (GPx), which neutralize and catalyze free radicals. Histopathological changes in mice testis were also studied. However, the co-treatments with PS significantly reduced these effects and promoted the reproductive parameters in male mice. In conclusion, PS exhibited protective effects against zinc and copper-induced reproductive toxicity, making it a potential adjuvant treatment for testicular toxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"897-907"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451547","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":"Fenfuro®-mediated arrest in the formation of protein-methyl glyoxal adducts: a new dimension in the anti-hyperglycemic potential of a novel fenugreek seed extract.","authors":"Samudra Prosad Banik, Pawan Kumar, Debasis Bagchi, Souradip Paul, Apurva Goel, Manashi Bagchi, Sanjoy Chakraborty","doi":"10.1080/15376516.2024.2358520","DOIUrl":"10.1080/15376516.2024.2358520","url":null,"abstract":"<p><p>The fenugreek plant (<i>Trigonella foenum</i>-<i>graecum</i>) is traditionally known for its anti-diabetic properties owing to its high content of furostanolic saponins, which can synergistically treat many human ailments. Non-enzymatic protein glycation leading to the formation of Advanced Glycation End products (AGE) is a common pathophysiology observed in diabetic or prediabetic individuals, which can initiate the development of neurodegenerative disorders. A potent cellular source of glycation is Methyl Glyoxal, a highly reactive dicarbonyl formed as a glycolytic byproduct. We demonstrate the <i>in vitro</i> glycation arresting potential of Fenfuro®, a novel patented formulation of Fenugreek seed extract with clinically proven anti-diabetic properties, in Methyl-Glyoxal (MGO) adducts of three abundant amyloidogenic cellular proteins, alpha-synuclein, Serum albumin, and Lysozyme. A 0.25% w/v Fenfuro<sup>®</sup> was able to effectively arrest glycation by more than 50% in all three proteins, as evidenced by AGE fluorescence. Glycation-induced amyloid formation was also arrested by more than 36%, 14% and 15% for BSA, Alpha-synuclein and Lysozyme respectively. An increase in MW by attachment of MGO was also partially prevented by Fenfuro<sup>®</sup> as confirmed by SDS-PAGE analysis. Glycation resulted in enhanced aggregation of the three proteins as revealed by Native PAGE and Dynamic Light Scattering. However, in the presence of Fenfuro<sup>®</sup>, aggregation was arrested substantially, and the normal size distribution was restored. The results cumulatively indicated the lesser explored potential of direct inhibition of glycation by fenugreek seed in addition to its proven role in alleviating insulin resistance. Fenfuro<sup>®</sup> boosts its therapeutic potential as an effective phytotherapeutic to arrest Type 2 diabetes.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"877-885"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237442","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}
Therese Featherston, Shaya Helem, Leon C D Smyth, Mark B Hampton, Martina Paumann-Page
{"title":"Comparing automated cell imaging with conventional methods of measuring cell proliferation and viability.","authors":"Therese Featherston, Shaya Helem, Leon C D Smyth, Mark B Hampton, Martina Paumann-Page","doi":"10.1080/15376516.2024.2360051","DOIUrl":"10.1080/15376516.2024.2360051","url":null,"abstract":"<p><p>The ability to assess cell proliferation and viability is essential for assessing new drug treatments, particularly in cancer drug discovery. This study describes a new method that uses a plate reader digital microscopy cell imaging and analysis system to assess cell proliferation and viability. This imaging system utilizes high throughput fluorescence microscopy with two fluorescent probes: cell membrane-impermeable SYTOX green and nuclear binding Hoechst-33342. Here we compare this technology to other known viability assays, namely: propidium iodide (PI)-based flow cytometry, and sulforhodamine B (SRB) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) based plate reader assays. These methods were assessed based on their effectiveness in detecting the cell numbers of two adherent cell lines and one suspension cell line. Automated cell imaging was most accurate at measuring cell number in both adherent and suspension cell lines. The PI-based flow cytometry method was more difficult to use with adherent cells, while the SRB and MTT assays had difficulties when monitoring cells in suspension. Despite these challenges, it was possible to obtain similar results when quantifying the effect of cytotoxic compounds. This study demonstrates that the digital microscopy automated cell imaging system is an effective method for assessing cell proliferation and the cytotoxic effect of compounds on both adherent and suspension cell lines.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"886-896"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroprotective effect of marrubiin against MPTP-induced experimental Parkinson's disease in male wistar rats.","authors":"Xiaofei Xu, Jingde Li, Mingjun Liu, Baoyan Zhang","doi":"10.1080/15376516.2024.2364191","DOIUrl":"10.1080/15376516.2024.2364191","url":null,"abstract":"<p><p>In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson's disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1β, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (<i>p</i> < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (<i>p</i> < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (<i>p</i> < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1β, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin's neuroprotective ability have to be studied in detail.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"908-919"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284816","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 organophosphates on precision-cut kidney slices.","authors":"C Hoeffner, F Worek, N Amend","doi":"10.1080/15376516.2024.2356184","DOIUrl":"10.1080/15376516.2024.2356184","url":null,"abstract":"<p><p>Organophosphate (OP) poisoning, both accidental and with suicidal intent, is a global medical challenge. While the primary toxicity of these pesticides is based on the inhibition of acetylcholinesterase (AChE), case reports describe patients developing OP-mediated renal insufficiency. We set out to investigate possible pathomechanisms utilizing rat precision-cut kidney slices (PCKS). Depending on the method of investigation, PCKS were observed for a maximum of 10 days. PCKS exposed to OP compounds (malaoxon, malathion, paraoxon, parathion) showed a dose-dependent loss of viability and a reduction of total protein content over the course of 10 days. A concentration of 500 µM OP showed the most differences between OP compounds. After two days of incubation parathion showed a significantly lower level of viability than malathion. The respective effects of paraoxon and malaoxon were not significantly different from the control. However, effects of OP were only observed in concentrations exceeding those that were needed to achieve significant AChE inhibition in rat kidney tissue. In addition, we observed histological changes, without inducing LDH leakage. Overall, results suggest that OP exert effects in kidney tissue, that exceed those expected from the sole inhibition of AChE and vary between compounds. Without signs of necrosis, findings call for studies that address other possible pathomechanisms, including inflammatory response, oxidative stress or activation of apoptosis to further understand the nephrotoxicity of OP compounds. Monitoring oxon concentration over time, we demonstrated reduced enzyme-inhibiting properties in the presence of PCKS, suggesting interactions between OP compound and kidney tissue.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"855-866"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923341","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}