Ayşegül Varol , Sabine M. Klauck , Susan P. Lees-Miller , Thomas Efferth
{"title":"Comprehensive transcriptomic analysis in wild-type and ATM knockout lung cancer cells: Influence of cisplatin on oxidative stress-induced senescence","authors":"Ayşegül Varol , Sabine M. Klauck , Susan P. Lees-Miller , Thomas Efferth","doi":"10.1016/j.cbi.2025.111563","DOIUrl":"10.1016/j.cbi.2025.111563","url":null,"abstract":"<div><div>Genetic mutations and impaired DNA repair mechanisms in cancer not only facilitate tumor progression but also reduce the effectiveness of chemotherapeutic agents, particularly cisplatin. Combination therapy has emerged as a promising strategy to overcome resistance. Comprehensive transcriptomic analyses, supported by integrated comparative bioinformatics and experimental approaches, are essential for identifying biomarkers and novel therapeutic targets underlying drug resistance. In this study, we performed overall survival and mutation analyses, examining 23 double-strand break repair proteins across more than 7500 tumors spanning 23 distinct cancer types. Our findings identify ATM (ataxia-telangiectasia mutated) as a key protein with the highest mutation frequency.</div><div>Using CRISPR/Cas9, we investigated the effects of ATM mutations on signalling pathways that influence the cellular response to cisplatin. ATM knockout enhanced cisplatin cytotoxicity by activating alternative cell death pathways, including oxidative stress-induced senescence and necroptosis. Microarray analysis revealed a regulatory interplay between ATM and NRF2 in the activation of oxidative stress-induced senescence. Specifically, ATM knockout promoted senescence by increasing reactive oxygen species (ROS) accumulation and downregulating NRF2 expression.</div><div>To enhance combination therapy, integrating genetic profiling with advanced tools such as CRISPR/Cas9 to target oxidative stress-induced senescence may provide innovative strategies to overcome drug resistance, thereby advancing personalized cancer treatment. These approaches lay the foundation for the development of personalized cancer therapies tailored to the unique mutational landscape of individual patients, offering promising prospects for improving treatment outcomes.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"418 ","pages":"Article 111563"},"PeriodicalIF":4.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yinan Wang , Songming He , Qin Huang , Jing Yang , Chaogang Yang , Jinli Ding
{"title":"The roles of YY1 in reproductive system: an overview","authors":"Yinan Wang , Songming He , Qin Huang , Jing Yang , Chaogang Yang , Jinli Ding","doi":"10.1016/j.cbi.2025.111560","DOIUrl":"10.1016/j.cbi.2025.111560","url":null,"abstract":"<div><div>Yin Yang 1 (YY1) is a highly conserved multifunctional transcription factor with multiple biological functions including cell proliferation, differentiation and transcriptional regulation. In recent years, the discovery of the functional activity of YY1 in the reproductive tissues of animals, including humans has attracted more and more attention. YY1 plays important roles in the development of follicular, embryo and placenta, as well as spermatogenesis. In addition, the role of YY1 in reproductive diseases including infertility, polycystic ovarian syndrome, recurrent spontaneous abortion (RSA), and gynecological tumor has been demonstrated. In the present review, we aimed to systematically introduce the expression and functions of YY1 in the reproductive system, providing new recommendations for future research areas.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"417 ","pages":"Article 111560"},"PeriodicalIF":4.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kun-Jie Bian , Xiaoze Bao , Xiao-Dong Li , Damien Bonne , Li-Wei Zou
{"title":"Recent progress of proline endopeptidase ligands and their effects on protein-protein interactions","authors":"Kun-Jie Bian , Xiaoze Bao , Xiao-Dong Li , Damien Bonne , Li-Wei Zou","doi":"10.1016/j.cbi.2025.111557","DOIUrl":"10.1016/j.cbi.2025.111557","url":null,"abstract":"<div><div>Proline endopeptidase (PREP), as a serine protease, plays a crucial role in human physiology and pathology, and is intricately linked to the genesis and progression of a spectrum of illnesses. The fluorescent substrates currently used for PREP lack ideal specificity and are unable to specifically detect PREP activity under physiological conditions. This limitation, to some extent, hinders the in-depth investigation of its physiological and pathophysiological functions. Beyond its enzymatic capabilities, PREP's physiological functions extend to the modulation of protein-protein interactions (PPIs), a dimension whose significance is only beginning to be recognized, and investigations into how PREP inhibitors might influence these PPIs remain sparse. Therefore, based on the outline of the distribution and structural characteristics of PREP, this review systematically summarized the structure-activity relationship (SAR) of PREP ligands concerning their potency and specificity, the associated recognition mechanisms, as well as the regulatory impact of PREP ligands on PPIs. Finally, the obstacles and future prospects of PREP ligands were emphasized, in order to provide suggestions and help for the design and development of PREP specific substrates and inhibitors.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"416 ","pages":"Article 111557"},"PeriodicalIF":4.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hui Xu , Jian Sun , Yu Zhao , Yaxiong Zhou , Kuan Wang , Xiang Liu , Jieyan Yang , Peng Wu , Shengkui Wang , John P. Kastelic , Weijie Qu , Limei Zhang , Xiaolong Gu
{"title":"PP2A attenuates α-amanitin-induced liver injury by promoting autophagy and inhibiting apoptosis in mouse models","authors":"Hui Xu , Jian Sun , Yu Zhao , Yaxiong Zhou , Kuan Wang , Xiang Liu , Jieyan Yang , Peng Wu , Shengkui Wang , John P. Kastelic , Weijie Qu , Limei Zhang , Xiaolong Gu","doi":"10.1016/j.cbi.2025.111558","DOIUrl":"10.1016/j.cbi.2025.111558","url":null,"abstract":"<div><div>Poisoning caused by the mushroom toxin α-amanitin accounts for ∼90 % of food poisoning deaths resulting from mushrooms in China. However, <em>Drosophila melanogaster</em> uses PP2A to mitigate effects of α-amanitin. Our objectives were to test the hypothesis that modulation of PP2A protects mammals against deleterious effects of α-amanitin. In <em>in vitro</em> experiments, α-amanitin significantly suppressed both gene and protein expression of PP2A. Inhibiting PP2A promoted apoptosis induced by α-amanitin while suppressing autophagy. <em>In vivo</em> α-amanitin increased liver coefficient and AST/ALT indexes, plus caused pathological changes, ultrastructural alterations, TUNEL-positive cells, and Cleaved-caspase-3 expression. Inhibiting PP2A activity worsened these end points, but increasing PP2A activity lessened them. Furthermore, α-amanitin reduced feed intake and body weight while increasing health scores and causing concentration-dependent mortality in mice. In contrast, enhancing PP2A significantly mitigated α-amanitin-induced effects on health with 100 % survival. In conclusion, targeting PP2A is a novel therapeutic approach to mitigate α-amanitin toxicity.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"417 ","pages":"Article 111558"},"PeriodicalIF":4.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nada S. Ibrahim , Eman Hatem Shoukry , Marwa Sharaky , Hadeer M. Diab , Ahmed H.M. Elwahy , Ismail A. Abdelhamid
{"title":"Synthesis, cytotoxicity, oxidative stress, anti-metastatic and anti-inflammatory effects of novel 2-methylene-1H-indene-1,3-dione tethered 2-(2-methoxyphenoxy)-N-arylacetamide: induction of apoptosis in HCT116 and HeLa cells","authors":"Nada S. Ibrahim , Eman Hatem Shoukry , Marwa Sharaky , Hadeer M. Diab , Ahmed H.M. Elwahy , Ismail A. Abdelhamid","doi":"10.1016/j.cbi.2025.111549","DOIUrl":"10.1016/j.cbi.2025.111549","url":null,"abstract":"<div><div>Six novel chalcones were synthesized, and their structures were confirmed using various spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against nine cancer and two normal cell lines. Compound <strong>7a</strong> showed the highest impact against colorectal carcinoma (HCT116) and cervical cancer (HeLa) with IC<sub>50</sub> values of 4.6 ± 0.03 and 5.5 ± 0.1 μg/mL, respectively, compared to doxorubicin (4.8 ± 0.4 and 5.7 ± 0.4 μg/mL, respectively). ELISA assay revealed that the apoptotic proteins (P53, Bax, caspases-3, -8, and -9) and the oxidative marker (Malondialdehyde (MDA)) were significantly activated in <strong>7a</strong> treated HCT116 and HeLa cells. However, the anti-metastatic markers (Matrix metalloproteinase 2 (MMP2) and Matrix metalloproteinase-9 (MMP9)), anti-apoptotic Bcl2, antioxidant Glutathione (GSH), and anti-inflammatory (interleukin (IL)-6, and IL-1β) were inhibited in HCT116 and HeLa cells treated with <strong>7a</strong>. Flow-cytometric analysis of the cell cycle revealed that the percentage of cells in S and G2/M phases in <strong>7a</strong> treated HCT116 cells was increased. After 24 h of treatment, Hela-treated cells had a slightly higher proportion of G0/G1 cells. Comet assay demonstrated that compound <strong>7a</strong> caused DNA damage with a percentage of 26.22 ± 1.1 % in HCT116 compared to the untreated cells (6.18 ± 0.88 %). Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of −22.7 and −23.3 kcal/mol, respectively, which confirmed our ELISA results.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"416 ","pages":"Article 111549"},"PeriodicalIF":4.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daijing Long , Yangfan Xu , Xuemei Li, Yilan Zeng, Ziting Tang, Lulu Liu, Yuanhong Liu, Xiule Zong, Shengbo Yang, Dan Wang
{"title":"TET2 promotes UVB-induced cell death by activating RIPK3-MLKL-necroptosis signaling","authors":"Daijing Long , Yangfan Xu , Xuemei Li, Yilan Zeng, Ziting Tang, Lulu Liu, Yuanhong Liu, Xiule Zong, Shengbo Yang, Dan Wang","doi":"10.1016/j.cbi.2025.111550","DOIUrl":"10.1016/j.cbi.2025.111550","url":null,"abstract":"<div><div>Ultraviolet B(UVB) radiation is a leading environmental factor that induces severe photodamage. However, its pathogenic mechanisms remain incompletely understood. Our previous research has found that Ten-eleven translocation 2 (TET2) is significantly upregulated in UVB-irradiated keratinocytes. Here, this study revealed that TET2 was upregulated in photodamaged skin, including specimens from actinic keratosis (AK) patients, UVB-exposed human skin sites, and a photodamaged mouse model. TET2 deficiency in keratinocytes mitigated UVB-induced cell death and photodamage, while TET2 overexpression exacerbated these effects. Furthermore, TET2 prompted keratinocyte death and photodamage mainly by activating the RIPK3-MLKL signaling pathway, with caspase-8 activation contributing secondarily. As for the mechanism, firstly, TET2 increases the expression of RIPK3 and MLKL by promoting their DNA demethylation, and secondly, TET2 directs the binding of PLK3 to RIPK3 and MLKL, thus enhancing the RIPK3-MLKL signaling pathway activation. This work showed that TET2 increases UVB-induced keratinocyte death and photodamage by activating the RIPK3-MLKL signaling pathway. TET2 appears to have a second function that orchestrates host responses to UVB exposure.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"416 ","pages":"Article 111550"},"PeriodicalIF":4.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Guo , Shanshan Meng , Jin Zhang , Ni Wang , Fengmei Guo
{"title":"Zn2+ regulates mitochondrial DNA efflux to inhibit AIM2-mediated ZBP1-PANoptosome pathway and alleviate septic myocardial injury","authors":"Jun Guo , Shanshan Meng , Jin Zhang , Ni Wang , Fengmei Guo","doi":"10.1016/j.cbi.2025.111525","DOIUrl":"10.1016/j.cbi.2025.111525","url":null,"abstract":"<div><div>This study was performed to investigate the mechanism by which zinc ion regulated mitochondrial DNA (mtDNA) efflux to inhibit the AIM2-mediated ZBP1-PANoptosome pathway and alleviate sepsis-induced myocardial injury. Here we discovered that zinc ions suppressed mitochondrial DNA release, thereby protecting the heart from LPS-induced damage in mice. In addition, LPS induced mPTP opening and mediated mtDNA efflux in cardiomyocytes, which drove AIM2 activation and ZBP1-PANoptosome multiprotein complex formation, leading to pan-apoptotic cardiomyocyte death. Zn<sup>2+</sup> prevented mPTP opening to inhibit mtDNA efflux-driven AIM2 and ZBP1-PANoptosome multiprotein complex formation and alleviate PANoptosis. Knockdown of AIM2 alleviated LPS-induced PANoptosis in cardiomyocytes. LPS-induced PANoptosis in cardiomyocytes by regulating the ZBP1/RIPK3 pathway. However, activation of the ZBP1/RIPK3 pathway partially reversed the inhibitory effect of Zn<sup>2+</sup> on PANoptosis in cardiomyocytes. Taken together, Zn<sup>2+</sup> regulated mitochondrial DNA efflux to inhibit the AIM2-mediated ZBP1-PANoptosome pathway to alleviate septic myocardial injury.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"417 ","pages":"Article 111525"},"PeriodicalIF":4.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Özgür Yılmaz , Yağmur Biliz , Sümeyra Ayan , Özge Çevik , Müfide Karahasanoğlu , Reyhan Çotuker , Naz Mina Mert Şahin , Kübra Gökkaya , Sevgi Gülyüz , Kemal Yelekçi , Ş. Güniz Küçükgüzel
{"title":"Design and synthesis of thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen as potential MetAP (type II) inhibitors","authors":"Özgür Yılmaz , Yağmur Biliz , Sümeyra Ayan , Özge Çevik , Müfide Karahasanoğlu , Reyhan Çotuker , Naz Mina Mert Şahin , Kübra Gökkaya , Sevgi Gülyüz , Kemal Yelekçi , Ş. Güniz Küçükgüzel","doi":"10.1016/j.cbi.2025.111555","DOIUrl":"10.1016/j.cbi.2025.111555","url":null,"abstract":"<div><div>In the present study, a range of novel thiosemicarbazides <strong>4a-i</strong> and 1,2,4-triazoles <strong>5a-i</strong> derived from ibuprofen, were synthesized. Structural elucidation of these synthesized compounds was performed utilizing a variety of spectroscopic methods, including FTIR, <sup>1</sup>H NMR, <sup>13</sup>C NMR and HR-MS. The synthesized compounds were tested for cytotoxicity in five different cancer cell lines (cervical cancer (HeLa), human breast cancer (MCF-7), human gastric adenocarcinoma (MKN-45), human metastatic prostate cancer (PC3) and human glioblastoma (U87)). The compounds were compared with healthy cells (NIH-3T3) and the most effective compounds were determined by means of the selectivity index. Thiosemicarbazides derived form ibuprofen <strong>4i</strong> and <strong>4d</strong> showed anticancer activity, while 1,2,4-triazoles derived form ibuprofen <strong>5b, 5c, 5d, 5e, 5h, 5g</strong> showed anticancer activity in HeLa, MCF-7, MKN-45, PC3 and U87 cells. To test the stability of the protein-drug complexes all 18 compounds <strong>4a-i</strong> and <strong>5a-i</strong> were docked into the active site of the MetAP2 enzyme In general, computational inhibition constants values were correlated with the experimental values. The dynamic behavior of MetAP2-inhibitor complexes was analyzed using all atoms Molecular Dynamic (MD) simulations for 200 ns duration. MD revealed that the drugs bind in the active center of MetAP2 with stable RMSD and RMSF. In conclusion, in-silico results and in-vitro studies suggests that thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen may be novel anticancer drug candidates for treating cervical, breast, prostate, gastric and glioblastoma. Compounds provided induction of apoptotic proteins in the cell by inhibiting MetAP2 enzyme. Furthermore, the potential antioxidant activities of the compounds were evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. Among the compounds tested, <strong>4a</strong>, <strong>4b</strong>, <strong>4e</strong>, <strong>4f</strong>, <strong>4h</strong>, and <strong>4i</strong> exhibited values closely resembling the DPPH activity of the standards.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"416 ","pages":"Article 111555"},"PeriodicalIF":4.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of acute organophosphate poisoning by using a cocaine hydrolase engineered from human butyrylcholinesterase","authors":"Johnathan E. LeSaint , Shurong Hou , Nellore Bhanu Chandar , Annet Kyomuhangi , Huimei Wei , Fang Zheng , Chang-Guo Zhan","doi":"10.1016/j.cbi.2025.111552","DOIUrl":"10.1016/j.cbi.2025.111552","url":null,"abstract":"<div><div>Organophosphate (OP) chemical warfare nerve agents and pesticides are potent, irreversible inhibitors of acetylcholinesterase (AChE), and paraoxon is often used as a surrogate compound in the studies of OP poisoning. For a truly effective treatment of OP poisoning, it is desirable that a protein-based OP bioscavenger can react with OP significantly faster than AChE reacting with OP to protect AChE from further inhibition reaction with OP. In the present study, our <em>in vitro</em> reactivity assays revealed that CocH3-Fc(M3), a potent cocaine hydrolase engineered from human butyrylcholinesterase (BChE), has a ∼20-fold improved bimolecular rate constant for the reaction with paraoxon compared to wild-type BChE. Due to the improved <em>in vitro</em> reactivity with paraoxon, CocH3-Fc(M3) at a modest dose of 25 mg/kg was able to effectively rescue all mice that had been injected with a lethal dose of 0.66 mg/kg paraoxon and accelerate the recovery of the mice from paraoxon-induced toxicity symptoms. All the <em>in silico</em>, <em>in vitro</em>, and <em>in vivo</em> data consistently suggest that CocH3-Fc(M3) can be used to effectively detoxify paraoxon.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"416 ","pages":"Article 111552"},"PeriodicalIF":4.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vesna Jaćević , Jelica Grujić-Milanović , Zoran Milovanović , Sladjan Milanović , Lana Nežić , Ljiljana Amidžić , Nataša Vojinović , Bojan Marković , Vladimir Dobričić , Petar Milosavljević , Eugenie Nepovimova , Kamil Kuča
{"title":"Determination of paraoxonase activity and prooxidant-antioxidant balance in the brain tissue of rats following subacute administration of different K-oximes","authors":"Vesna Jaćević , Jelica Grujić-Milanović , Zoran Milovanović , Sladjan Milanović , Lana Nežić , Ljiljana Amidžić , Nataša Vojinović , Bojan Marković , Vladimir Dobričić , Petar Milosavljević , Eugenie Nepovimova , Kamil Kuča","doi":"10.1016/j.cbi.2025.111539","DOIUrl":"10.1016/j.cbi.2025.111539","url":null,"abstract":"<div><div>This study aimed to determine the paraoxonase activity and prooxidant-antioxidant balance in the brain tissue of Wistar rats following subacute treatment with selected K-oximes. Each K-oxime was administered intramuscularly (0.1 LD<sub>50</sub>/kg) twice per week for four weeks, and 7 days after the last treatment, the paraoxonase activity (PON1), the prooxidant-antioxidant balance (PAB), the levels of superoxide anion radical (O<sub>2</sub><sup>•–</sup>), the concentration of nitrite (NO<sub>2</sub><sup>−</sup>) and the content of free protein thiol groups in the brain homogenates were evaluated. The PON1 and PAB activity were significantly reduced in almost all oxime-treated groups (<em>p</em> < 0.01 and <em>p</em> < 0.001, respectively). The concentrations of O<sub>2</sub><sup>•–</sup> were significantly increased in the obidoxime-, K048-, K074- and K075-treated groups (<em>p</em> < 0.001), while the levels of NO<sub>2</sub><sup>−</sup> was significantly decreased in asoxime-, obidoxime-, K074 and K075-treated rats (<em>p</em> < 0.01, <em>p</em> < 0.001, respectively). The content of Thiol groups was significantly elevated in all oxime-treated groups (<em>p</em> < 0.001). Continuing our previously published data, these results confirmed that applied K-oximes improved the oxidative status and further harmful systemic effects of rats after subacute administration.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"416 ","pages":"Article 111539"},"PeriodicalIF":4.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}