Drug and Chemical Toxicology最新文献

{"title":"Analysis of key targets for 5-hydroxymethyl-2-furfural-induced lung cancer based on network toxicology, network informatics, and <i>in vitro</i> experiments.","authors":"Tianchi Zhuang, Chang Gao, Wei Zeng, Wenwu Zhao, Hairong Yu, Shen Chen, Jiemiao Shen, Minghui Ji","doi":"10.1080/01480545.2024.2384442","DOIUrl":"10.1080/01480545.2024.2384442","url":null,"abstract":"<p><p>5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through <i>in vitro</i> experiments. By using ChEMBL, STITCH, GeneCards, and OMIM databases, 51 toxic targets were identified. GO and KEGG enrichment analyses indicated a strong correlation between toxic targets and lung cancer. Through protein-protein interaction (PPI) analysis, MAPK3, MAPK1, and SRC were identified as key targets implicated in 5-HMF-induced lung cancer. The HPA database showed high expression of these three key targets in lung cancer tissues. Kaplan-Meier database demonstrated that the higher expression of these key targets in lung cancer patients was associated with a poorer prognosis. The TIMER database revealed that the high expression of these key targets had a significant impact on the level of immune cell infiltration in lung cancer, particularly impacting CD4+ T cells and macrophages. Finaly, in <i>In vitro</i> experiments demonstrated that prolonged exposure to 5-HMF induced malignant transformation of BEAS-2B cells and the upregulation of key targets. The findings suggest that 5-HMF is a contributing factor in the development of lung cancer, with MAPK3, MAPK1, and SRC potentially playing crucial roles in this process.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"451-461"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787555","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":"Computational and experimental study of terpolymers: spectroscopic, thermal, thermochemical, molecular property, and <i>in silico</i> toxicity analysis.","authors":"Nevin Çankaya, Mehmet Hanifi Kebiroglu, Cengiz Soykan","doi":"10.1080/01480545.2025.2468924","DOIUrl":"https://doi.org/10.1080/01480545.2025.2468924","url":null,"abstract":"<p><p>In this study, a comprehensive analysis of the CMA2OEM-co-DVB-co-AMPS (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-2-acrylamido-2-methyl-1-propanesulfonic acid) and CMA2OEM-co-DVB-co-VIM (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-vinylimidazole) terpolymers was conducted. The structural and chemical properties of the terpolymers were examined using Fourier transform infrared (FT-IR) spectroscopy, frontier molecular orbital analysis, molecular electrostatic potential (MEP) maps, ¹H, and ¹³C NMR spectroscopy, thermochemistry surface maps (TCSM), toxicity assessments, physical properties, electron localization function (ELF), and total electrostatic potential (ESP) analyses. <i>In silico</i> toxicity analyses, a quantitative structure-activity relationship (QSAR) model was used for Toxicity Estimation Software Tool (TEST) and ProTox 3.0, a web-based virtual toxicity laboratory, was used for oral toxicity prediction. Toxicity estimates using TEST showed that both terpolymers exhibited low toxicity profiles. Oral toxicity prediction emphasizes that CMA2OEM-co-DVB-co-VIM may pose a greater risk compared to CMA2OEM-co-DVB-co-AMPS. In addition, experimental thermal characterization of these terpolymers was also performed. These comprehensive analyses have provided significant insights into the potential applications and functional properties of the terpolymers.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527933","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":"Antioxidant capacity, acute and sub-acute oral toxicity, and <i>in vivo</i> anti-inflammatory effects of <i>Tetradenia riparia</i> hydroalcoholic extract.","authors":"Martin Ndayambaje, Thierry Habyarimana, Hicham Wahnou, Aimable Nsanzurwimo, Oumaima Chgari, Pacifique Ndishimye, Asmaa Mezty, Mernissi Farida, Mehdi Karkouri, Younes Zaid, Abdallah Naya, Mounia Oudghiri","doi":"10.1080/01480545.2025.2468932","DOIUrl":"https://doi.org/10.1080/01480545.2025.2468932","url":null,"abstract":"<p><p><i>Tetradenia riparia (T. riparia</i>) is a medicinal plant native to sub-Saharan Africa, traditionally used but has limited <i>in vivo</i> scientific validation. This study evaluated its antioxidant, toxicity, and anti-inflammatory effects using <i>in vivo</i> toxicity tests, paw edema, air pouch models, and vascular permeability assessment. Additionally, qualitative phytochemical analysis and quantitative measurements of total polyphenolic and flavonoid content were conducted. <i>In vitro</i> assays revealed significant concentrations of polyphenolic and flavonoid compounds, demonstrating notable radical scavenging activities in DPPH, phosphomolybdate, and FRAP assays. <i>In vivo</i> studies demonstrated that <i>T. riparia</i> extract showed no indications of acute or sub-acute oral toxicity, even when administered at the highest tested dosage of 5000 mg/kg body weight (LD50 > 5000 mg/kg). Toxicity assessments confirmed its safety, showing no fatalities, significant organ damage as evidenced by histopathological analysis, or substantial adverse effects on most hematological and biochemical parameters. The hydroalcoholic extract of <i>T. riparia</i> demonstrated a notable anti-inflammatory effect that increased with dosage. The inhibition percentage of paw edema by the extract was high at 3 hours, reaching 39.13 ± 8.78%. Nitric oxide (NO) inhibition at doses of 0.5 g/kg and 1 g/kg was recorded as 36.09 ± 2.13% and 49.96 ± 5.41%, respectively. Regarding vascular permeability, <i>T. riparia</i> extract significantly reduced dye leakage (p < 0.05 and p < 0.001), with inhibition percentages of 61.57% and 75.25% at doses of 0.5 g/kg and 1 g/kg, respectively. These findings highlight its promising potential as a treatment for inflammatory disorders. In conclusion, phytochemical analysis identified compounds, which are believed to be responsible for the pharmacological effects observed. Further studies are needed to investigate the chronic consumption of hydroalcoholic extract for long-term isolate bioactive compounds, understand their mechanisms, ensure comprehensive safety profiles for potential drug development, and elucidate their anti-inflammatory mechanism.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482492","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":"Damage to the sarcoplasmic reticulum by venom of the Mexican black-tailed rattlesnake (<i>Crotalus molossus nigrescens</i>): inhibition of the Ca²⁺-ATPase and membrane lipid disruption.","authors":"Luis Fernando Plenge-Tellechea, David Meléndez-Martínez, César Emmanuel Rivas-Valles, Ana Gatica-Colima, Martha Sandra Cruz-Pérez, Jorge A Sierra-Fonseca","doi":"10.1080/01480545.2025.2463369","DOIUrl":"https://doi.org/10.1080/01480545.2025.2463369","url":null,"abstract":"<p><p>Snakebite envenomation is a public health problem in many areas in the world and is a significant cause of disability and death. Crotalid venoms consist of a cocktail of peptides and enzymes that can cause myonecrotoxic lesions, which are associated with irreversible loss of muscle tissue. The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) is a transmembrane protein with a critical role in maintaining cellular Ca²⁺ homeostasis, which is central in facilitating skeletal and cardiac muscle contraction/relaxation. Crotalid venom-induced myotoxicity has been linked to alterations in the intracellular levels of Ca²⁺. However, the specific mechanisms, including SERCA's involvement, are poorly understood. Thus, we investigated the <i>in vitro</i> toxic effect of crotalid venom on the enzymatic activity of SERCA, using venom of the Mexican black-tailed rattlesnake, <i>Crotalus molossus nigrescens</i>, (v<i>Cmn</i>), and SERCA-enriched sarcoplasmic reticulum (SR) microsomes from rabbit skeletal muscle as experimental models. Enzymatic assays revealed significant v<i>Cmn</i>-induced decreases in SERCA activity in a time- and dose-dependent manner. Thin layer chromatography and phospholipid hydrolysis measurements showed significant SR membrane damage. The results suggest that v<i>Cmn</i> affects SERCA functionality and compromises the integrity of the SR membrane, both of which are critical for skeletal muscle function and could thus be key mediators of v<i>Cmn</i>-induced myotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381753","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":"Mitigative and neuroprotective effects of <i>Lavandula angustifolia</i> essential oil on serotonin syndrome-induced neurotoxicity in male albino rats.","authors":"Manal A Babaker, Naema Ibolgasm Alazabi, Shimaa A Haredy, Ayman Mohamed Algohary, Mai M Anwar, Einas M Yousef, Omar A Ahmed-Farid","doi":"10.1080/01480545.2025.2458618","DOIUrl":"https://doi.org/10.1080/01480545.2025.2458618","url":null,"abstract":"<p><p>The term serotonin syndrome (SS) is a potentially life-threatening devastating condition triggered by the excessive accumulation of serotonin, often due to an overdose or the concurrent use of multiple serotonergic drugs. <i>Lavandula angustifolia</i> (lavender), a known plant from the Lamiaceae family, is very rich in essential oils, minerals, and tannins. This study aimed to elucidate the detrimental effects of SS on the brain and to evaluate the neuroprotective potential of <i>L. angustifolia</i> essential oil. Male rats were randomly divided into the following groups: control (Group 1); <i>L. angustifolia</i>-treated (Group 2); ondansetron-treated high-dose (Group 3); sertraline-treated high-dose (Group 4); low-dose ondansetron + sertraline-treated (Group 5); high-dose ondansetron + sertraline-treated (Group 6); low-dose ondansetron + sertraline + <i>L. angustifolia</i>-treated (Group 7); and high-dose ondansetron + sertraline + <i>L. angustifolia</i>-treated (Group 8). Neurotransmitter levels, dopamine metabolites, and expressed cytokines were quantified. Additionally, histological assessment of the hippocampus was performed. The results revealed significant disruptions in neurotransmitter and amino acid levels within the hippocampus across the treated groups. Notably, the high-dose ondansetron + sertraline group presented pronounced increases in serotonin, 5-HIAA, and proinflammatory cytokines, resulting in neurotoxicity and pronounced alterations in the hippocampus. Conversely, treatment with <i>L. angustifolia</i> significantly attenuated these neurotoxic effects. The findings suggest that <i>L. angustifolia</i> confers neuroprotection against the deleterious effects of SS, particularly by counteracting the neurotoxic impact of combined serotonin 5-HT3 receptor antagonists and serotonin reuptake inhibitors within the hippocampus. These findings highlight the potential of <i>L. angustifolia</i> as a natural therapeutic agent for mitigating SS-induced neurotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-19"},"PeriodicalIF":2.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078911","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":"Effect of adenosine triphosphate on methylphenidate-induced oxidative and inflammatory kidney damage in rats.","authors":"Bahtinur Yeter, Zeynep Suleyman, Seval Bulut, Betul Cicek, Taha Abdulkadir Coban, Ozlem Demir, Halis Suleyman","doi":"10.1080/01480545.2025.2457386","DOIUrl":"https://doi.org/10.1080/01480545.2025.2457386","url":null,"abstract":"<p><p>The purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied <i>via</i> oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064437","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":"Pre-clinical acute oral toxicity and subacute neurotoxicity risk assessments on sprague dawley rats treated with single dose or repeated doses of flavonoid-enriched fraction extracted from <i>Oroxylum indicum</i> leaves.","authors":"Farah Amna Othman, Anani Aila Mat Zin, Yusmazura Zakaria, Nik Nur Hakimah Nik Salleh, Asmaa' Mohd Satar, Suat Cheng Tan","doi":"10.1080/01480545.2024.2449210","DOIUrl":"https://doi.org/10.1080/01480545.2024.2449210","url":null,"abstract":"<p><p><i>Oroxylum indicum</i> possesses promising flavonoid secondary metabolites. However, translation of these compounds into clinical practice for neurological disease treatment is halted as the toxicity and safety profile of the plant extracts are yet to be determined. This study was conducted to assess the acute oral toxicity and subacute neurotoxicity that could be imposed by the flavonoid-enriched fraction (FEF) extracted from <i>O. indicum</i> leaves, by strictly following the procedures set in Organization for Economic Co-operation and Development (OECD) Guidelines No.420 and 424. It was found that at the highest dosage (2000 mg/kg b.wt), no death or toxicity-related behavioral changes were observed. No significant alteration in hematological and serum biochemical parameters beyond the standard laboratory range was observed. Detailed histopathological examination, as verified by clinical pathologist, revealed absence of detectable inflammation, changes in any macroscopic and microscopic tissue abnormalities in all vital organ of the treated rats. Moreover, neurological functional test of rats treated with repeated doses of FEF for 28 d also showed absence of neurological abnormality, suggesting negative long term side effects of this fraction on the animal. In conclusion, this study presented valuable pre-clinical safety validation of a high-quality herbal medicinal product, setting the foundation for its future application in clinical setting.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064472","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":"Humic acid attenuates cisplatin-induced nephrotoxicity in rats.","authors":"Ender Tekes, Meltem Ickin Gulen, Coskun Silan, Aysel Guven Bagla","doi":"10.1080/01480545.2025.2453590","DOIUrl":"https://doi.org/10.1080/01480545.2025.2453590","url":null,"abstract":"<p><p>Cisplatin-induced nephrotoxicity, a major limitation of this chemotherapeutic agent, involves oxidative stress, inflammation, and apoptosis. This study investigated the potential renoprotective effects of humic acid in a rat model of cisplatin-induced nephrotoxicity. Forty-two male Wistar rats were assigned to six groups: control, humic acid, cisplatin, cisplatin + humic acid 10 mg/kg, cisplatin + humic acid 20 mg/kg, and cisplatin + humic acid 40 mg/kg. On day 7, the rats were sacrificed, and cardiac blood and kidneys were collected for biochemical and histopathological examinations. Humic acid administration significantly attenuated the cisplatin-induced increases in renal TNF-α and NF-κB levels, indicating a reduction in inflammation. Humic acid also ameliorated histopathological damage, including Bowman's capsule dilatation, tubular cell degeneration, and hemorrhage. However, humic acid did not significantly alter oxidative stress parameters or caspase-3 levels. Humic acid demonstrates a protective effect against cisplatin-induced nephrotoxicity in rats, primarily by mitigating the inflammatory response. While HA's beneficial effects on oxidative stress and apoptosis were limited in this study, its ability to reduce inflammation highlights its potential as a therapeutic strategy to mitigate cisplatin-induced kidney injury.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051965","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":"<i>In silico</i> molecular docking and <i>in vitro</i> analysis of atomoxetine.","authors":"Nurullah Bolat, Merve Meliha Hız-Çelikliyurt, Erhan Akıncı, Gülsüm Akkuş, Melih Günay, Şükrü Alperen Korkmaz","doi":"10.1080/01480545.2025.2452859","DOIUrl":"10.1080/01480545.2025.2452859","url":null,"abstract":"<p><p>Although atomoxetine, a selective norepinephrine reuptake inhibitor, is widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD), there is limited data on its cytogenetic effects. This study aimed to investigate the cytotoxicity and genotoxicity of atomoxetine <i>in vitro</i> and <i>silico</i>. Chromosome aberration and micronucleus assays were used to analyze the genotoxic effect of atomoxetine in human peripheral blood lymphocytes under culture conditions. The mitotic index was assessed for cytotoxic potential. For the docking analysis, DNA receptor (1BNA) was prepared with ChimeraX, and the Atomoxetine molecule was optimized by Avogadro2.0 software. <i>In silico</i> molecular docking analysis was carried out utilizing SwissDock online platform. The results obtained were visualized using ChimeraX and Pymol software. Atomoxetine doses of 9.6 µg/mL (equal to about 1.2 mg/kg as a maintenance dose), 14.4 µg/mL (equal about to 1.8 mg/kg as the highest dose systematically tested), 48.0 µg/mL (equal about to 6 mg/kg as five times the maintenance dose) and 96.0 µg/mL (equal about to 12 mg/kg as ten times the maintenance dose) were analyzed. The findings clearly indicate that atomoxetine has no genotoxic effect at the therapeutic dose. However, we observed genotoxic effects at 48.0 and 96.0 µg/mL doses. No strong binding affinity occurs <i>in silico</i> analyses. As one of the initial inquiries into the <i>in silico</i> and <i>in vitro</i> appraisal of atomoxetine's genotoxic impacts, the research has established that atomoxetine does not significantly affect the frequency of chromosomal damage or micronucleus formation. Genotoxic effects should be kept in mind at doses above clinical practice.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051962","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":"Novel chlorinated oxime K870 protects rats against paraoxon poisoning better than obidoxime.","authors":"Žana M Maksimović, Sonja T Marinković, Đorđe Đukanović, Nebojša Mandić-Kovačević, Snežana Uletilović, Mladen Duran, Kamil Kuča, Kamil Musilek, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković","doi":"10.1080/01480545.2025.2454279","DOIUrl":"https://doi.org/10.1080/01480545.2025.2454279","url":null,"abstract":"<p><p>The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD₅₀ values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD₅₀) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051970","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}