Chemico-Biological Interactions最新文献

{"title":"Pantothenic acid alleviates osteoarthritis progression by inhibiting inflammatory response and ferroptosis through the SIRT1/Nrf2 signaling pathway","authors":"Yi Liu ,&nbsp;Yang Wang ,&nbsp;Shengqi Cheng ,&nbsp;Jie Mu ,&nbsp;Guanchen Yin ,&nbsp;Hang Gao","doi":"10.1016/j.cbi.2025.111494","DOIUrl":"10.1016/j.cbi.2025.111494","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease that is a major cause of deformity, swelling, pain and even loss of function in the knee joints of the elderly. Pantothenic acid (PA) plays a protective role in many organs due to its antioxidant and anti-inflammatory properties. Herein, we aimed to assess the protective role of PA on osteoarthritis and investigate the underlying molecular mechanism. The levels of inflammatory factors (IL-1β and TNF-α) in knee tissues were measured by ELISA. The Safranin O-Fast Green staining was used to assess the severity of OA and the H&amp;E staining was used to assess the degree of synovitis. In vitro, the levels of iron, MDA, GSH were measured by the detection kits. Western blotting was used to assess the levels of signaling-related proteins. Our results showed that PA significantly attenuated the degree of cartilage degeneration in the MIA-induced osteoarthritis model. PA also reduced the expression of IL-1β, TNF-α, MMP1 and MMP3. In vitro, PA effectively reduced the concentrations of MMP1 and MMP3 in IL-1β-stimulated chondrocytes. PA decreased the levels of Fe²⁺ and MDA, while increasing GSH production and GPX4 and SLC7A11 expression in IL-1β-induced chondrocytes. Meanwhile, we found that PA was able to inhibit the phosphorylation level of p65, IκB protein in chondrocytes, which effectively blocked the NF-κB signaling pathway. Furthermore, PA also increased the level of SIRT1, Nrf2, and HO-1 protein expression. In addition, the inhibition of PA on IL-1β-induced MMPs production and ferroptosis were inhibited by the SIRT1 inhibitor EX-527. In conclusion, PA inhibited chondrocyte ferroptosis and cartilage destruction in osteoarthritis. The mechanism was through activating SIRT1/Nrf2 signaling pathway.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111494"},"PeriodicalIF":4.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738251","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":"ADME profile of AP-238 - opioid designer drug (CAS: 140924-11-4): first application of multi-in silico approach methodology for comprehensive prediction of ADME profile (absorption, distribution, metabolism and excretion) important for clinical toxicology and forensic purposes","authors":"Kamil Jurowski ,&nbsp;Alicja Krośniak","doi":"10.1016/j.cbi.2025.111493","DOIUrl":"10.1016/j.cbi.2025.111493","url":null,"abstract":"<div><div>AP-238 is a recently emerged opioid designer drug from the cinnamylpiperazine class, raising increasing concern in forensic and clinical toxicology due to its potential for abuse and limited ADME (absorption, distribution, metabolism, and excretion) profile. This study presents the first comprehensive prediction of the ADME parameters for AP-238 using a multi-<em>in silico</em> approach. Multiple <em>in silico</em> methods (SwissADME, ACD/Percepta, pkCSM, ADMETlab 3.0, ADMET Predictor 12.0, Simulation Plus, XenoSite, and DruMAP) were employed to estimate key ADME parameters. Results indicate high gastrointestinal absorption and blood-brain barrier permeability, suggesting strong psychoactive potential. AP-238 exhibits pH-dependent solubility and interacts variably with P-glycoprotein, which may affect its systemic and central nervous system exposure. Distribution modeling revealed moderate to extensive tissue penetration and significant plasma protein binding. Metabolic simulations identified 11 primary metabolites and involvement of major CYP isoforms (including CYP2B6, CYP2C19, CYP2D6, CYP3A4). Excretion predictions suggest a rapid elimination primarily via hepatic routes. This study provides critical pharmacokinetic insight into AP-238, supporting its early toxicological assessment and prioritization for further investigation. The applied <em>in silico</em> strategy demonstrates a rapid, ethical alternative to traditional ADME testing, particularly valuable in the context of novel synthetic opioids.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"415 ","pages":"Article 111493"},"PeriodicalIF":4.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744677","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":"Enhancing cardiac safety: Liposomal ciprofloxacin mitigates anthracycline-induced cardiotoxicity without compromising anticancer efficacy","authors":"Olga Swiech ,&nbsp;Anna Boguszewska-Czubara","doi":"10.1016/j.cbi.2025.111496","DOIUrl":"10.1016/j.cbi.2025.111496","url":null,"abstract":"<div><div>Anthracyclines, such as doxorubicin and epirubicin (EPI), are integral in the treatment of solid tumors and hematological malignancies but are associated with cardiotoxicity, potentially leading to heart failure. The underlying mechanisms involve the generation of reactive oxygen species (ROS), alterations in iron metabolism, and the inhibition of topoisomerase 2β (Top2β), resulting in mitochondrial dysfunction and cell death. Fluoroquinolones, including ciprofloxacin (CPX), enhance the efficacy of anthracyclines by inhibiting topoisomerase II and inducing apoptosis, thereby indicating a promising combination therapy. This study investigated the impact of environmental pH on the cardiotoxicity and myocardial accumulation of anthracyclines, as well as the cardioprotective and synergistic potential of CPX when co-administered with epirubicin. The findings revealed that only the zwitterionic form of CPX, either free or encapsulated in liposomes, offers significant cardioprotection without compromising the anticancer activity of EPI. Remarkably, the combination of liposomal CPX and EPI completely attenuates EPI's cardiotoxicity. These results suggest that initiating treatment with liposomal CPX prior to EPI administration may optimize cardioprotection while maintaining therapeutic efficacy against cancer.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"414 ","pages":"Article 111496"},"PeriodicalIF":4.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of bromodomain and extra-terminal (BET) proteins with JQ1 exacerbates acetaminophen-induced hepatotoxicity by altering detoxification pathways and oxidative stress responses","authors":"A.P. Laddha ,&nbsp;A. Seyednejad ,&nbsp;A.C. Donepudi ,&nbsp;M.J. Goedken ,&nbsp;J.E. Manautou ,&nbsp;G.C. Sartor","doi":"10.1016/j.cbi.2025.111491","DOIUrl":"10.1016/j.cbi.2025.111491","url":null,"abstract":"<div><div>Acetaminophen (APAP) is a widely used over-the-counter drug for the treatment of fever and pain. At therapeutic doses, APAP has a relatively safe profile. However, at supratherapeutic doses it can produce liver injury and even fatal hepatotoxicity. Antioxidant genes regulated by the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor, erythroid 2-like 2 (NRF2) pathway play a crucial role in hepatoprotection against APAP-induced hepatotoxicity and oxidative stress. Recent studies suggest that bromodomain and extra-terminal motif (BET) proteins, epigenetic readers, act as putative regulators of the KEAP1-NRF2 pathway, but their role in acute drug-induced liver injury (DILI) remains unclear. In this study, we employed complementary <em>in vitro</em> and <em>in vivo</em> approaches utilizing pharmacological inhibition and gene knockdown techniques to examine the role of BET proteins in APAP-induced toxicity. Our findings indicate that APAP treatment significantly alters the gene and protein expression of BET proteins in both mouse liver and the HC-04 cell line. Cytotoxicity analysis using lactate dehydrogenase (LDH) leakage assay revealed that treatment with the small molecule BET inhibitor JQ1 did not alter APAP-induced cytotoxicity. However, siRNA-mediated knockdown of the BET genes <em>Brd3</em> and <em>Brd4</em>, but not <em>Brd2</em>, reduced APAP-induced cytotoxicity in HC-04 cells. In hepatic gene expression analysis experiments, JQ1 pretreatment in mice activated the <em>Nrf2</em> pathway and altered antioxidant genes such as <em>Gclc</em>, <em>Gclm</em>, <em>Ho-1</em>, and <em>Txnrd1</em>, suggesting an enhancement of cellular defenses against APAP-induced oxidative stress at 12 h timepoint. However, by 24 h, histopathological findings revealed significant liver necrosis and inflammation in the JQ1-APAP treated group, indicating that while BET inhibition may confer early protection, it may not fully prevent long-term liver injury.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111491"},"PeriodicalIF":4.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744679","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":"Pre-clinical evidence for mitochondria as a therapeutic target for luteolin: A mechanistic view","authors":"Marcos Roberto de Oliveira","doi":"10.1016/j.cbi.2025.111492","DOIUrl":"10.1016/j.cbi.2025.111492","url":null,"abstract":"<div><div>Pre-clinical evidence indicates that mitochondria may be a therapeutic target for luteolin (3′,4’,5,7-tetrahydroxyflavone; LUT) in different conditions. LUT modulates mitochondrial physiology in <em>in vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> experimental models. This flavone exerted mitochondria-related antioxidant and anti-apoptotic effects, stimulated mitochondrial fusion and fission, induced mitophagy, and promoted mitochondrial biogenesis in human and animal cells and tissues. Moreover, LUT modulated the activity of components of the oxidative phosphorylation (OXPHOS) system, improving the ability of mitochondria to produce adenosine triphosphate (ATP) in certain circumstances. The mechanism of action by which LUT promoted mitochondrial benefits and protection are not completely clear yet. Nonetheless, LUT is a potential candidate to be utilized in mitochondrial therapy in the future. In this work, it is explored the mechanisms of action by which LUT modulates mitochondrial physiology in different pre-clinical experimental models.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111492"},"PeriodicalIF":4.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726237","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":"Flavonoids and their role in oxidative stress, inflammation, and human diseases","authors":"Klaudia Jomova ,&nbsp;Suliman Y. Alomar ,&nbsp;Richard Valko ,&nbsp;Jan Liska ,&nbsp;Eugenie Nepovimova ,&nbsp;Kamil Kuca ,&nbsp;Marian Valko","doi":"10.1016/j.cbi.2025.111489","DOIUrl":"10.1016/j.cbi.2025.111489","url":null,"abstract":"<div><div>Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2<img>C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2–related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111489"},"PeriodicalIF":4.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of novel aldose reductase inhibitor drug on gut microbiota composition and metabolic health in ZDF 'lean' rats","authors":"Marek Lepáček ,&nbsp;Pavol Boďo ,&nbsp;Marta Šoltésová Prnová ,&nbsp;Mária Bučková ,&nbsp;Domenico Pangallo ,&nbsp;Jelena Pavlović","doi":"10.1016/j.cbi.2025.111490","DOIUrl":"10.1016/j.cbi.2025.111490","url":null,"abstract":"<div><div>A novel multi-target drug, cemtirestat, inhibiting aldose reductase (ALR2) has been developed to prevent secondary diabetic complications and act as an antioxidant against hyperglycemia-related processes. This study examines cemtirestat's impact on gut microbiome composition, drug metabolism, and therapeutic efficacy in male Zucker diabetic fatty (ZDF) \"Lean\" rats. Rats were divided into the control group (C) and the treated group (T), which received 7.7 mg/kg/day cemtirestat for two months, with weekly monitoring of food, fluid intake, and weight gain. Stool, urine, and plasma samples were analyzed biochemically, and fecal DNA was sequenced using Oxford Nanopore Technology. Treated rats exhibited less weight gain, likely due to cemtirestat's antioxidant effects. Biochemical analyses revealed no significant changes in glucose, liver enzymes, or cholesterol. Although there was a slight increase in alanine aminotransferase (ALT), our study found that levels of other liver enzymes such as aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin remained within normal limits, suggesting the observed increase in ALT was not indicative of drug-induced liver injury. LefSe microbiome analysis revealed an enrichment of beneficial bacteria like <em>Blautia</em> and <em>Faecalibacterium</em> in treated rats. Microbial community structure did not distinctly separate treated from control groups, but differences emerged over time. DeSeq2 analysis identified varying genera abundances over weeks, with treated samples enriched in beneficial bacteria by Week 8. Correlation analysis linked plasma insulin levels positively with <em>Prevotella</em> and negatively with <em>Clostridium</em> and <em>Lactobacillus</em>. Cemtirestat's impact on weight and microbiota suggests the potential to improve gut health. Further research is required to uncover cemtirestat's mechanism in diabetes management, drug metabolism, and therapeutic efficacy.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111490"},"PeriodicalIF":4.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor AMSP-30 m attenuates CCl4-induced liver fibrosis in mice by inhibiting the sonic hedgehog pathway","authors":"Lili Lu ,&nbsp;Yuchen Ma ,&nbsp;Qing Tao ,&nbsp;Jing Xie ,&nbsp;Xiao Liu ,&nbsp;Yongkang Wu ,&nbsp;Yang Zhang ,&nbsp;Xiuli Xie ,&nbsp;Mingming Liu ,&nbsp;Yong Jin","doi":"10.1016/j.cbi.2025.111480","DOIUrl":"10.1016/j.cbi.2025.111480","url":null,"abstract":"<div><div>Liver fibrosis is a passive and irreversible wound healing process caused by chronic liver injury. Research has shown that the upregulation of hypoxia inducible factor-1 alpha (HIF-1α) is closely related to the occurrence and development of liver fibrosis and HIF-1 α may be a promising target for the treatment of liver fibrosis. AMSP-30 m is a newly developed novel HIF-1α inhibitor by our group, which has strong anti-tumor and anti-inflammatory effects. In this study, we described the therapeutic effect and specific mechanism of AMSP-30 m on carbon tetrachloride (CCl₄) induced liver fibrosis in mice. Liver fibrosis induced by CCl₄ in mice and liver fibrosis induced by cobalt dichloride (CoCl₂) in LX-2 cells (human hepatic stellate cell (HSC) line) were studied. Hematoxylin &amp; eosin (H&amp;E)and Masson's trichrome staining were used to observe pathological conditions. Western Blot, immunofluorescence and immunohistochemistry were used to detect protein expression and localization in cells, and quantitative real-time PCR analysis (qRT-PCR) was used to detect mRNA expression. Biochemical detection kits were used to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The results demonstrated that AMSP-30 m significantly alleviated pathological symptoms, reduced ALT and AST levels, and inhibited the expression of alpha-smooth muscle actin (α-SMA) and collagen type I (COL1α1) in CCl₄-induced liver fibrosis in mice. AMSP-30 m could significantly reduce the expression of HIF-1α and sonic hedgehog (Shh) pathway related proteins (Smoothened (Smo), Shh, and glioma-associated oncogene-1 (Gli-1)) in CCl₄ induced liver fibrosis mice. AMSP-30 m also played a similar role in the CoCl₂-induced anoxic liver fibrosis model of LX-2 cells<strong>.</strong> Further experiments showed that Cyclopamine (a Shh inhibitor) could significantly inhibit the increase of α-SMA and COL1α1 resulting from HIF-1α but not significantly inhibit HIF-1α induced by CoCl₂ in LX-2 cells. And the combination of Cyclopamine and AMSP-30 m further reduced the expression of α-SMA and COL1α1 induced by HIF-1α. In summary, this study demonstrates that the HIF-1α inhibitor AMSP-30 m exerts a robust anti-fibrotic effect by inhibiting the Shh pathway, which is identified as a critical underlying mechanism. These findings suggest a promising therapeutic strategy for the treatment of liver fibrosis.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111480"},"PeriodicalIF":4.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672016","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":"Role of the interleukin-33 (IL-33)/suppressor of tumorigenicity 2 (ST2) signaling in superoxide anion-triggered inflammation and pain behavior in mice","authors":"Sergio M. Borghi ,&nbsp;Thacyana T. Carvalho ,&nbsp;Mariana M. Bertozzi ,&nbsp;Cátia C.F. Bernardy ,&nbsp;Ana C. Zarpelon ,&nbsp;Felipe A. Pinho-Ribeiro ,&nbsp;Cássia Calixto-Campos ,&nbsp;Victor Fattori ,&nbsp;José C. Alves-Filho ,&nbsp;Thiago M. Cunha ,&nbsp;Fernando Q. Cunha ,&nbsp;Rubia Casagrande ,&nbsp;Waldiceu A. Verri Jr.","doi":"10.1016/j.cbi.2025.111476","DOIUrl":"10.1016/j.cbi.2025.111476","url":null,"abstract":"<div><div>Reactive oxygen species such as superoxide anion have varied roles in inflammation and pain, which can be mimicked by potassium superoxide (KO₂), the superoxide anion donor. Interleukin (IL)-33 has pleiotropic functions by activating its receptor suppression of tumorigenicity 2 (ST2). However, the role of IL-33/ST2 signaling in inflammatory pain initiated by reactive oxygen species (ROS) such as superoxide anion has not been investigated, which was the aim of the present study. IL-33 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Mechanical and thermal hyperalgesia and overt pain were evaluated by electronic von Frey, hot plate, and abdominal writhing/paw flinching/licking, respectively. Edema and leukocyte recruitment (myeloperoxidase assay and total/differential cell count), antioxidant capacity, superoxide anion production and lipid peroxidation were assessed. Paw skin and spinal cord messenger ribonucleic acid (mRNA) expression of pro-inflammatory mediators and glial markers in the spinal cord were evaluated. Immunofluorescence was used to detect spinal glial and neuronal c-Fos activation. KO₂ injection triggered IL-33 production in the paw skin and spinal cord of mice, induced hyperalgesia, edema, neutrophil recruitment to the paw tissue, overt pain-like behavior, and leukocyte recruitment to the peritoneum that were reduced in ST2 deficient mice. In the paw skin and spinal cord, KO₂ triggered IL-33/ST2-dependent oxidative stress, and mRNA expression of inflammatory molecules, which were reduced by ST2 deficiency. KO₂ induced spinal cord glial (at mRNA/protein levels) and neuronal activation in IL-33/ST2-dependent manner. IL-33/ST2 signaling mediates, at least in part, superoxide anion-induced inflammatory pain by modulating local and spinal inflammatory events.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"413 ","pages":"Article 111476"},"PeriodicalIF":4.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643627","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":"A MALDI-MSI-based approach to characterize the spatial distribution of cylindrospermopsin and lipid alterations in rat intestinal tissue","authors":"Antonio Casas-Rodríguez ,&nbsp;Cristina María López-Vázquez ,&nbsp;Remedios Guzmán-Guillén ,&nbsp;Nahúm Ayala ,&nbsp;Ana María Cameán ,&nbsp;Angeles Jos ,&nbsp;Eduardo Chicano-Gálvez","doi":"10.1016/j.cbi.2025.111479","DOIUrl":"10.1016/j.cbi.2025.111479","url":null,"abstract":"<div><div>Global warming and eutrophication of water bodies are driving the increase in cyanobacterial blooms, which produce toxins such as cylindrospermopsin (CYN). This compound has multiple toxic effects, and following CYN exposure, its distribution in the body varies, particularly in organs such as the liver and kidneys, suggesting its potential for bioaccumulation in key tissues. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-MSI) enables visualization of the spatial distribution of a wide range of molecules. In this study, using MALDI-MSI, a new method was developed and optimized for the detection of CYN, and its quantitative spatiotemporal distribution was analyzed for the first time in intestinal samples from rats orally exposed to this toxin (500 μg/kg body weight) and sacrificed 0, 2, 4, 6 and 24 h after exposure. Furthermore, the impact of CYN on the intestinal lipid profile was evaluated. The method was validated in terms of linearity, sensitivity, and precision, measuring CYN in mimetic tissue sections at different concentrations (1–100 ppm), allowing its successful application to visualize CYN distribution in rat intestines. The results revealed alterations in different lipid families involved in the inflammatory response, increased oxidative stress, and progressive damage to the integrity of the cell membrane.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"412 ","pages":"Article 111479"},"PeriodicalIF":4.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635032","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}