Pei-Yi Wu , Ulfah Hasanah , Sheng-Hua Yang , Sin-Yi Chen , Yueh-Hsia Luo , Chien-Chin Chen , Ssu-Ching Chen
{"title":"Enhancing cisplatin efficacy in hepatocellular carcinoma with selenocystine: The suppression of DNA repair and inhibition of proliferation in hepatoma cells","authors":"Pei-Yi Wu , Ulfah Hasanah , Sheng-Hua Yang , Sin-Yi Chen , Yueh-Hsia Luo , Chien-Chin Chen , Ssu-Ching Chen","doi":"10.1016/j.cbi.2024.111291","DOIUrl":"10.1016/j.cbi.2024.111291","url":null,"abstract":"<div><div>Cisplatin (cDDP) is a crucial chemotherapy drug for treating various cancers, including hepatocellular carcinoma (HCC). However, its effectiveness is often hindered by side effects and drug resistance. Selenocystine (SeC) demonstrates potential as an anticancer agent, particularly by inhibiting DNA repair mechanisms. This study explored the synergistic potential of SeC combined with cDDP for treating HCC. Our results show that SeC pretreatment followed by cDDP significantly suppresses HCC cell proliferation more effectively than either treatment alone, with minimal toxicity to normal liver cells. The combination induces significant DNA damage by inhibiting homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Xenograft experiments confirmed that the combined therapy strongly inhibits tumor growth. SeC boost the effectiveness of cDDP by amplifying DNA damage and inhibiting DNA repair, presenting a promising approach to enhancing liver cancer treatment.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"405 ","pages":"Article 111291"},"PeriodicalIF":4.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514628","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}
Jiaying Huang , Fengxia Liu , Tao Qi , Rufei Gao , Hongye Xie , Lingyan Ruan , Junlin He , Fangfang Li , Taihang Liu , Hanting Xu , Xuemei Chen
{"title":"Benzo(a)pyrene promotes autophagy to impair endometrial decidualization via inhibiting CXCL12/CXCR4 axis","authors":"Jiaying Huang , Fengxia Liu , Tao Qi , Rufei Gao , Hongye Xie , Lingyan Ruan , Junlin He , Fangfang Li , Taihang Liu , Hanting Xu , Xuemei Chen","doi":"10.1016/j.cbi.2024.111288","DOIUrl":"10.1016/j.cbi.2024.111288","url":null,"abstract":"<div><div>Benzo(a)pyrene (BaP), a pervasive environmental pollutant with endocrine-disrupting properties, has been associated with detrimental effects on pregnancy. During early pregnancy, the endometrial decidualization process is critical for embryo implantation. Abnormal decidualization can lead to implantation failure, aberrant placental formation, and pregnancy loss. We previously revealed that BaP exposure impaired decidualization and implantation in mice, yet the underlying mechanisms remained elusive. Autophagy, a cellular mechanism pivotal for energy and material recycling, contributes to the decidualization process. The chemokine C-X-C motif chemokine ligand 12 (CXCL12), secreted by endometrium stromal cells (ESCs), is involved in regulating endometrial decidualization and autophagy. Therefore, this study aimed to explore the hypothesis that BaP disrupts the decidualization process by interfering with autophagic pathways via the CXCL12/CXCR4 axis during early pregnancy. We found that BaP inhibited CXCL12/CXCR4 expression, and induced autophagy by promoting autophagosome formation, which in turn impaired the decidualization in early pregnant mice uterus and decidual stromal cells (DSCs). Using autophagy inhibitors 3-methyladenine and chloroquine in combination with BaP to treat DSCs, successfully weakened BaP-induced autophagy, and relieved decidual injury. Additionally, activation of CXCL12/CXCR4 by recombinant protein CXCL12 attenuated BaP-induced autophagy, inhibited the PI3K/AKT signal activation caused by BaP, and partly rescued the expression of decidualization-related genes. In summary, this study demonstrates that BaP induces autophagy in DSCs by inhibiting the CXCL12/CXCR4 axis, leading to damage in endometrial decidualization during early pregnancy. The findings provide a critical chemokine-mediated regulatory mechanism involved in embryo implantation and contribute valuable knowledge to the reproductive toxicology of BaP.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"405 ","pages":"Article 111288"},"PeriodicalIF":4.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514627","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}
Aleksandra Owczarzy , Monika Trzepacz , Karolina Kulig , Wojciech Rogóż , Andrzej Zięba , Małgorzata Maciążek-Jurczyk
{"title":"In vitro spectroscopic studies of 9-amino-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride with main carrier plasma proteins","authors":"Aleksandra Owczarzy , Monika Trzepacz , Karolina Kulig , Wojciech Rogóż , Andrzej Zięba , Małgorzata Maciążek-Jurczyk","doi":"10.1016/j.cbi.2024.111289","DOIUrl":"10.1016/j.cbi.2024.111289","url":null,"abstract":"<div><div>Current methods of cancer treatment, particularly chemotherapy, are associated with harmful side effects. For this reason, it is significant to study new substances with anticancer potential with the highest possible efficacy and the lowest possible side effects. The aim of the study was the spectroscopic analysis of the interaction between 9-amino-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride (Salt3) and main carrier proteins, such as human serum albumin (HSA), α1 acid glycoprotein (AGP), human γ globulin (HGG) and controlled normal serum (CNS).</div><div>The association constants (K<sub>a</sub> [mol·L<sup>−1</sup>]) and the number of binding site classes (n) for the binding of Salt3 with studied carrier proteins and controlled normal serum were calculated using the Klotz equation. To study HSA and AGP high affinity binding sites, the fluorescent markers were used. Spectral parameter A and the second derivative of differential absorption spectra were used to assess environmental changes around aromatic amino acids residues. The changes in HSA and AGP secondary structure in the complexes with Salt3 were evaluated using the analysis using circular dichroism.</div><div>Salt3 slightly binds to HSA, AGP, HGG molecules and CNS. In addition, Salt3 affects the tertiary structure of the studied proteins, while it does not damage the secondary structure of the main carrier proteins responsible for Salt3 distribution in the bloodstream.</div><div>Because Salt3 binds weakly to model carrier proteins and normal control serum, it can lead to both strong therapeutic and toxic effects. Considering these preliminary spectroscopic studies, additional tests as well as expanding research to include other techniques seem justified.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"405 ","pages":"Article 111289"},"PeriodicalIF":4.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514639","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":"6:2 chlorinated polyfluoroalkyl ether sulfonate (F–53B) induced nephrotoxicity associated with oxidative stress, inflammation and fibrosis in mice","authors":"Hua Wu , Yueying Feng , Ruiying Zhang , Hengyi Xu , Fen Fu","doi":"10.1016/j.cbi.2024.111290","DOIUrl":"10.1016/j.cbi.2024.111290","url":null,"abstract":"<div><div>6:2 Chlorinated polyfluoroalkyl ether sulfonate (trade name F–53B) is a substitute for perfluorooctane sulfonate (PFOS) used in the plating industry, and has been found in a range of environmental matrices and livings. There are numerous ways by which it is biotoxic to mammals. The kidneys are critical for maintaining homeostasis. However, little research has been conducted on how F–53B affects the kidneys. In this work, we investigated the renal toxicity of long-term oral F–53B treatment in C57BL/6J mice. Mice were allowed to drink F–53B freely at concentrations of 0, 0.057, 0.57, and 5.7 mg/L for 8 weeks. Renal oxidative stress, inflammation, and fibrosis were detected in mice exposed to F–53B, and the expression of related biochemical markers was significantly altered. Further investigations revealed that the TGF-β1/Smad3 and NF-κB signaling pathways may be associated with F–53B-induced renal fibrotic damage and inflammation. Overall, this study suggested that F–53B causes renal injury possibly <em>via</em> oxidative stress, activating the TGF-β1/Smad3 and NF-κB signaling pathways. This provides a foundation for further research into the harmful mechanism of F–53B in mammals.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"405 ","pages":"Article 111290"},"PeriodicalIF":4.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514626","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":"Synthesis and characterization of 7-diethylamino-4-Chloromethyl coumarin: Spectroscopic analysis, molecular docking, and anticancer activity on large intestine carcinoma cells","authors":"Hakan Beyaztas , Kubra Bozali , Sumeyye Koc , Mucahit Ozdemir , Bahattin Yalcin , Eray Metin Guler","doi":"10.1016/j.cbi.2024.111287","DOIUrl":"10.1016/j.cbi.2024.111287","url":null,"abstract":"<div><div>Cancer, characterized by uncontrolled cell growth and metastasis, poses a significant global health burden, ranking as a leading cause of mortality worldwide. Colorectal cancer (CRC) specifically accounts for a substantial portion of cancer cases, with increasing incidence projected over the coming decades. While conventional treatments exist, they often entail adverse effects and limited efficacy, driving interest in natural remedies like coumarin derivatives due to their diverse biological activities and perceived safety profile. This study focuses on the synthesis and characterization of a novel compound, 7-diethylamino-4-chloromethyl coumarin (referred to as 7D4C), derived from coumarin. Structural elucidation employed Fourier transform infrared spectroscopy (FT-IR), proton and carbon-13 nuclear magnetic resonance spectroscopy (<sup>1</sup>H and <sup>13</sup>C NMR), and mass spectrometry (MALDI-TOF-MS). Molecular docking studies were conducted to explore potential biological interactions. Furthermore, the anti-cancer potential of 7D4C was assessed using human epithelial adenocarcinom (LoVo) and healthy fibroblast (CCD-18Co) cell lines. Viability analysis, comet assay for DNA damage, and evaluation of cancer biomarkers including apoptosis, intracellular reactive oxygen species (iROS) levels, mitochondrial membrane potential (MMP), intracellular glutathione (GSH) concentration, and intracellular calcium (iCa<sup>2+</sup>) levels were performed. The synthesis of 7D4C was successfully completed, and its structure was confirmed. Molecular docking results indicate that 7D4C exhibits strong binding affinity to the p53 protein, highlighting its potential as a novel modulator of p53 activity. Subsequent investigations revealed that the synthesized compound induced apoptosis in cancer cells by reducing MMP and triggering DNA damage through the production of iROS. The promising anti-cancer activity of 7D4C in the LoVo cell line highlights its importance in coumarin-based therapies. Introducing 7D4C could significantly enhance future research in this area, leveraging insights from <em>in vitro</em> coumarin studies.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111287"},"PeriodicalIF":4.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514642","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}
Paloma Begines , Alessandro Bonardi , Simone Giovannuzzi , Alessio Nocentini , Paola Gratteri , Viviana De Luca , Aday González-Bakker , José M. Padrón , Clemente Capasso , Claudiu T. Supuran
{"title":"Synthesis and investigation of selective human carbonic anhydrase IX, XII inhibitors using coumarins bearing a sulfonamide or biotin moiety","authors":"Paloma Begines , Alessandro Bonardi , Simone Giovannuzzi , Alessio Nocentini , Paola Gratteri , Viviana De Luca , Aday González-Bakker , José M. Padrón , Clemente Capasso , Claudiu T. Supuran","doi":"10.1016/j.cbi.2024.111284","DOIUrl":"10.1016/j.cbi.2024.111284","url":null,"abstract":"<div><div>The role of carbonic anhydrases isoforms (CAs) IX and XII in the pathogenesis and progression of many types of solid tumors is well known. In this context, selective CA inhibitors (CAIs) towards the mentioned isoforms is a validated strategy for the development of agents to target cancer. For this purpose, novel coumarin derivatives based on the hybridization with arylsulfonamide or biotin scaffolds were synthesized and tested as inhibitors of four different human carbonic anhydrases isoforms: hCA I, II, IX and XII. Coumarin-sulfonamide derived <strong>27</strong>, with a thiourea moiety and triazole as linker, showed the highest inhibition activity against hCA XII with an inhibition constant (K<sub>I</sub>) of 7.5 nM and afforded a very good selectivity over hCA I. Compound <strong>32</strong> was the most potent inhibitor against hCA IX (K<sub>I</sub> = 6.3 nM), 4-fold stronger than the drug acetazolamide AAZ (K<sub>I</sub> = 25 nM), used herein as a reference compound, and showed remarkable selectivity over hCA I and II. The coumarin-biotin derivatives <strong>37</strong>–<strong>39</strong> showed outstanding selectivity towards on-target enzymes (hCA IX and XII) and appear as plausible leads for designing of CAIs.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111284"},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514641","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}
Na Young Kim , Divakar Vishwanath , Shreeja Basappa , Keshav Kumar Harish , Mahendra Madegowda , Kanchugarakoppal S. Rangappa , Basappa Basappa , Kwang Seok Ahn
{"title":"Isoxazole based nucleosides induce autophagy through the production of ROS and the suppression of the β-catenin pathway in human colorectal carcinoma cells","authors":"Na Young Kim , Divakar Vishwanath , Shreeja Basappa , Keshav Kumar Harish , Mahendra Madegowda , Kanchugarakoppal S. Rangappa , Basappa Basappa , Kwang Seok Ahn","doi":"10.1016/j.cbi.2024.111285","DOIUrl":"10.1016/j.cbi.2024.111285","url":null,"abstract":"<div><div>β-catenin is frequently implicated in signaling pathways that regulate autophagy, and the production of reactive oxygen species (ROS) has been linked to autophagy activation. Isoxazole-based nucleoside compounds have demonstrated anti-cancer properties. In this study, we report the identification of novel isoxazole-nucleosides as anti-tumor agents and their impact on autophagy in human colorectal carcinoma (CRC) cells. Among the ITP series, ITP-7 and ITP-9 (ITP-7/9) exhibited significant cytotoxicity compared to other compounds. Treatment with ITP-7/9 upregulated the expression of key autophagy-related proteins, including LC3 II, Atg7, and phosphorylated Beclin-1. Additionally, ITP-7/9 promoted the formation of LC3 II puncta and increased the number of AO-stained and MDC-stained cells, indicating enhanced autophagy. ROS levels were elevated following ITP-7/9 exposure, and treatment with N-acetyl <span>l</span>-cysteine (NAC), a ROS inhibitor, reduced the ITP-7/9-induced expression of LC3 II. Furthermore, ITP-7/9 inhibited β-catenin's role as a transcription factor, as observed in ICC assays. Moreover, cells with <em>β-catenin</em> gene deletion exhibited stronger autophagy when treated with ITP-7/9 compared to those treated with ITP-7/9 alone. These findings suggest that ITP-7/9 induces autophagy and promotes CRC cell death by downregulating β-catenin.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111285"},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514640","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}
Huilin Li , Yanying Zhou , Chenghui Cai , Hangfei Liang , Xuan Li , Min Huang , Shicheng Fan , Huichang Bi
{"title":"Fenofibrate induces liver enlargement in aging mice via activating the PPARα-YAP signaling pathway","authors":"Huilin Li , Yanying Zhou , Chenghui Cai , Hangfei Liang , Xuan Li , Min Huang , Shicheng Fan , Huichang Bi","doi":"10.1016/j.cbi.2024.111286","DOIUrl":"10.1016/j.cbi.2024.111286","url":null,"abstract":"<div><div>Fenofibrate is a clinically prescribed drug for treating hypertriglyceridemia, which is also a classic peroxisome proliferator-activated receptor α (PPARα) agonist. We previously reported that fenofibrate induced liver enlargement in adult mice partially through activation of the yes-associated protein (YAP) signaling pathway. However, the effects of fenofibrate on liver enlargement and the YAP signaling pathway in aging mice remain unclear. In this study, D-galactose-induced aging mice, naturally aging mice, and senescence-accelerated mice P8 (SAMP8) were used to investigate the effects of aging on fenofibrate-induced liver enlargement and YAP signaling activation. The results showed that fenofibrate-induced liver enlargement in aging mice was consistent with that of adult mice. The effects of fenofibrate on hepatocyte enlargement around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area were comparable between adult and aging mice. There was no significant difference in the upregulation of PPARα downstream proteins between the two groups following fenofibrate treatment. Fenofibrate treatment also increased the expression of proliferation-related proteins and activated the YAP signaling pathway to a similar degree in both groups. In summary, these results demonstrate that the fenofibrate-induced liver enlargement and activation of the YAP pathway are consistent between adult and aging mice, indicating that the effects of fenofibrate on promoting liver enlargement and its activation of the PPARα and YAP pathway were independent of aging. These findings offer a new perspective for the clinical use of fenofibrate in elderly patients and provide a new insight for the role of PPARα in liver enlargement.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"405 ","pages":"Article 111286"},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514629","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}
Marija Živanović , Milica Selaković , Aleksandar Pavić , Života Selaković , Bogdan Šolaja , Juan F. Santibanez , Tatjana Srdić-Rajić
{"title":"Unveiling the 4-aminoquinoline derivatives as potent agents against pancreatic ductal adenocarcinoma (PDAC) cell lines","authors":"Marija Živanović , Milica Selaković , Aleksandar Pavić , Života Selaković , Bogdan Šolaja , Juan F. Santibanez , Tatjana Srdić-Rajić","doi":"10.1016/j.cbi.2024.111281","DOIUrl":"10.1016/j.cbi.2024.111281","url":null,"abstract":"<div><div>Common antimalarials such as artemisinins, chloroquine and their derivatives also possess potent anti-inflamantory, antiviral and anticancer properties. In the search for new therapeutics to combat difficult-to-treat pancreatic carcinomas, we unveiled that 4-aminoquinoline derivatives, with significant antiplasmodial properties and a great safety profile <em>in vivo</em>, have remarkable anticancer activity against pancreatic ductal adenocarcinoma (PDAC) and considerable efficacy in the xenograft model <em>in vivo</em>. The aim of the present study was to further investigate anticancer properties of these compounds in a drug-repurposing manner. The compounds showed profound cytotoxic effects at nanomolar to low micromolar concentration in 2D cultured cells (<em>in vitro</em>) and in the zebrafish PDAC xenograft model (<em>in vivo</em>). A deeper insight into their mechanisms of cytotoxic action showed these compounds induce apoptosis while increasing reactive oxygen species levels along with autophagy inhibition. Additional investigation of the autophagy modulation proved that tested quinoline derivatives cause P62 and LC3-II accumulation in PDAC cells alongside lysosomal alkalinization. Further, <em>in vivo</em> toxicity studies in the zebrafish model showed low toxicity without developmental side effects of the investigated 4-aminoquinolines, while the applied compounds effectively inhibited tumor growth and prevented the metastasis of xenografted pancreatic cells. Taken together, these results highlight the 4-aminoquinolines as privileged structures that ought to be investigated further for potential application in pancreatic carcinoma treatment.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111281"},"PeriodicalIF":4.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483066","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}
Peter P. Smith , Ilaria J. Chicca , Jennifer L.J. Heaney , Maria Muchova , Farhat L. Khanim , Adrian M. Shields , Mark T. Drayson , Iain L.C. Chapple , Josefine Hirschfeld
{"title":"Paracetamol suppresses neutrophilic oxygen radicals through competitive inhibition and scavenging","authors":"Peter P. Smith , Ilaria J. Chicca , Jennifer L.J. Heaney , Maria Muchova , Farhat L. Khanim , Adrian M. Shields , Mark T. Drayson , Iain L.C. Chapple , Josefine Hirschfeld","doi":"10.1016/j.cbi.2024.111283","DOIUrl":"10.1016/j.cbi.2024.111283","url":null,"abstract":"<div><div>Neutrophils, pivotal cells of innate and adaptive immune responses, employ reactive oxygen species (ROS) to combat pathogens and control gene expression. Paracetamol (acetaminophen) is widely used as an analgesic and antipyretic medication, yet its precise mechanisms of action are not yet fully understood. Here, we investigate the impact of both ingested and <em>in-vitro</em> paracetamol on neutrophil ROS activity, using flow cytometry and antioxidant assays. Our studies reveal that paracetamol significantly suppresses ROS activity <em>ex-vivo</em> in the short term. Additionally, both paracetamol and its metabolite N-acetyl-<em>p</em>-benzoquinone imine exhibited direct <em>in vitro</em> antioxidant effects, and paracetamol suppressed neutrophil extracellular trap formation <em>ex vivo</em>. These findings suggest a connection between paracetamol use and altered neutrophil responses, with potential implications for use in some patient groups, such as immunocompromised individuals. Further investigation into paracetamol's effects on neutrophil antimicrobial functions is warranted to elucidate possible risks, particularly when taken frequently or in conjunction with other treatments such as vaccinations.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111283"},"PeriodicalIF":4.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483065","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}