Antioxidants最新文献

{"title":"Castalin Induces ROS Production, Leading to DNA Damage and Increasing the Activity of CHK1 Inhibitor in Cancer Cell Lines.","authors":"Margherita D'Angelo, Annamaria Medugno, Maria Cuomo, Maria Carmen Ragosta, Andrea Russo, Giulio Mazzarotti, Giuseppe Maria Napolitano, Carmelina Antonella Iannuzzi, Francesco Errichiello, Luigi Frusciante, Martino Forino, Raffaele Cucciniello, Canio Martinelli, Annamaria Salvati, Domenico Memoli, Giovanni Nassa, Enrico Bucci, Michelino De Laurentiis, Antonio Giordano, Luigi Alfano","doi":"10.3390/antiox14091096","DOIUrl":"10.3390/antiox14091096","url":null,"abstract":"<p><p>(1) Background: The use of cancer therapy is one of the most challenging arguments in cancer research and is in constant development. One of the principal problems connected with tumor therapy arises from the potential side effects connected with the classical chemotherapeutic treatment but also with molecular target therapy. The identification of novel molecules useful for the reduction of potential side effects but also as a new therapeutic opportunity is one of the hottest topics. (2) Methods: We identified castalin from chestnut shells by using NRM and LC-MS/MS. We treated different cancer cell lines with castalin alone or in combination with a CHK1 inhibitor. Finally, we performed an RNA-seq analysis of HeLa cells treated with castalin. (3) Results: We demonstrated the ability of castalin to induce DNA damage, probably by increasing ROS production. Consistently, antioxidant treatment, with ascorbic acid, reduced the DNA damage induced by castalin. Finally, we demonstrated the potential synergistic effect of castalin with SRA737, a CHK1 inhibitor currently used in clinical trials. (4) Conclusions: We demonstrated the ability of castalin to induce DNA damage favoring NHEJ repair. Moreover, the use of castalin in combination with SRA737 increased the efficacy of the CHK1 inhibitor, reducing its possible side effects.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172524","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":"Integrated Lipidomics and Network Pharmacology Reveal the AMPK-Mediated Therapeutic Mechanism of 3,3'-Diindolylmethane in Hepatic Lipid Metabolism.","authors":"Xudong Li, Yunfeng Lin, Ruomei Niu, Siyuan Chen, Jingyun Pan, Yuquan Zhong, Junqiang Du, Qiuxia Dong, Hongfeng Zhang, Heng Fang, Huiyang Zhu, Wei Zhu","doi":"10.3390/antiox14091093","DOIUrl":"10.3390/antiox14091093","url":null,"abstract":"<p><p>Dysregulation of hepatic lipid metabolism constitutes a central mechanism in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). 3,3'-Diindolylmethane (DIM), a bioactive compound abundant in dietary Brassica vegetables, exhibited protective effects on hepatocellular carcinoma and metabolic/inflammatory pathologies. Nevertheless, the effects of DIM on hepatic lipid metabolism and its underlying mechanisms remain unclear. Administration of DIM (50 mg/kg bw/day) prevented oxidative stress and hepatic lipid deposition in both high-fat diet (HFD)-fed wild-type (WT) and ob/ob mice. Lipidomics revealed that DIM diminished the lipogenesis and reshaped the hepatic lipid profile. Network pharmacology analysis identified the AMPK signaling pathway as the underlying mechanistic target for DIM in treating MASLD. In both HepG2 cells and mouse primary hepatocytes (MPH), DIM attenuated palmitic acid (PA)-induced cellular lipid accumulation, ROS generation, and reduction in oxygen consumption rate (OCR). These protective effects of DIM were diminished by co-treatment with Compound C (CC), a specific AMPK inhibitor. DIM administration enhanced AMPKα phosphorylation in vivo (WT/ob/ob mice) and in vitro (HepG2/MPH), concomitant with PPARα upregulation and SREBP1/ACC1 downregulation. CC abolished all DIM-induced molecular changes in vitro. Collectively, DIM alleviates hepatic lipid accumulation and oxidative stress in MASLD models through AMPK activation, subsequently modulating PPARα and SREBP1/ACC1 pathways.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172479","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":"Epigallocatechin Gallate Ameliorates Granulosa Cell Developmental via the Eukaryotic Initiation Factor 2 Alpha/Activating Transcription Factor 4 Pathway in Hyperthyroid Female Rats.","authors":"Ying Sun, Mingqi Wu, Haoyuan Feng, Yilin Yao, Rui Chen, Yanzhou Yang, Cheng Zhang","doi":"10.3390/antiox14091092","DOIUrl":"10.3390/antiox14091092","url":null,"abstract":"<p><p>Follicular development is recognized as a highly complex biological process regulated by multiple factors. Thyroid hormone (TH) is considered one of the key regulators of female reproduction, and its dysregulation can significantly impair follicular development. Epigallocatechin gallate (EGCG), the main active component of green tea, possesses strong antioxidant properties. Numerous studies have demonstrated that EGCG positively influences reproductive function in both humans and animals. However, whether EGCG directly affects follicular development under conditions of TH dysregulation remains poorly understood. The primary objective of this study was to investigate the impact of hyperthyroidism on ovarian development, examine whether EGCG could mitigate the adverse effects of TH dysregulation, and elucidate the underlying molecular mechanisms. In the T₄-induced hyperthyroidism rat model, ovarian tissues were serially sectioned for Hematoxylin-Eosin (HE) and Masson's trichrome staining to assess morphological changes, and follicle numbers were quantified at each developmental stage. Granulosa cell (GC) viability, proliferation, and apoptosis induced by T₃ were evaluated using CCK8, EdU, and TUNEL assays, respectively. Antioxidant enzyme activity was measured, and the expression levels of related proteins were analyzed via Western blotting. Results showed that hyperthyroidism altered ovarian structure, significantly increasing the number of atretic follicles. Levels of antioxidant enzymes, including Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-PX), and Catalase (CAT), were markedly decreased, whereas the lipid peroxidation product malondialdehyde (MDA) was significantly elevated. Furthermore, all ERS-related proteins, phosphorylated Eukaryotic Initiation Factor 2 Alpha (p-eIF2α), Activating Transcription Factor 4 (ATF4), C/EBP homologous protein (CHOP), and Caspase-3, were upregulated, accompanied by decreased glucose-regulated protein 78 (GRP78) expression. Treatment with EGCG alleviated these detrimental effects of hyperthyroidism. At the cellular level, high concentrations of T₃ reduced GC viability and proliferation while increasing apoptosis. Reactive oxygen species levels were elevated, and GRP78 expression was decreased. Notably, all T₃-induced effects were reversed by EGCG treatment. In summary, this study demonstrates that hyperthyroidism induces oxidative stress in GCs, which triggers endoplasmic reticulum stress via the eIF2α/ATF4 pathway and leads to apoptosis. EGCG mitigates apoptosis by enhancing antioxidant capacity, thereby preserving ovarian function. These findings establish EGCG as a protective agent for maintaining ovarian health and fertility.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172315","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":"Synthesis, Characterization, Antioxidant Activity, Antibacterial Activity, and Cytotoxicity of Quaternized Inulin Derivatives Bearing Aromatic Amides.","authors":"Yuan Chen, Yingqi Mi, Zhanyong Guo, Hongwu Zhang","doi":"10.3390/antiox14091091","DOIUrl":"10.3390/antiox14091091","url":null,"abstract":"<p><p>In this study, a total of 12 new quaternized inulin (QIL) derivatives bearing aromatic amides were synthesized according to the ion exchange method. All the derivatives exhibited higher antioxidant activities in scavenging hydroxyl radicals, DPPH radicals, and superoxide radicals compared to pure inulin. Most of the derivatives could fully eliminate hydroxyl radicals at 1.6 mg/mL. Meanwhile, QIL derivatives exhibited increased antibacterial activity against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> compared to unmodified inulin. The structure-function relationship of the synthesized derivatives was discussed. Moreover, assays conducted with L929 cells (mouse fibroblasts) by the cell counting kit-8 (CCK-8) method did not show toxicities for the derivatives. Thus, the derivatives show promise for biomedical materials, functional foods, and pharmaceutical applications because they combine excellent antioxidant and antibacterial activities without exhibiting cytotoxicity.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172586","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":"Polynucleotide HPT^TM-Based Hydrogels Exhibit Scavenging Activity Against Reactive Oxygen Species.","authors":"Maria Teresa Colangelo, Silvana Belletti, Stefano Guizzardi, Carlo Galli","doi":"10.3390/antiox14091089","DOIUrl":"10.3390/antiox14091089","url":null,"abstract":"<p><p>This study investigates the scavenger activity of Polynucleotide High Purification Technology (PN HPT^TM), alone or in combination with hyaluronic acid (PN HPT^TM + HA) against oxidative stress induced by hydrogen peroxide (H₂O₂). Since oxidative stress is implicated in numerous pathological conditions, identifying effective antioxidants is crucial for therapeutic development. We employed a cell-free fluorometric assay based on Calcein-AM, a fluorescence probe whose signal increases proportionally to the generation of reactive oxygen species (ROS), to evaluate the ability to neutralize ROS under varying oxidative stress conditions and determine the dose- and time-dependent effects of these compounds. PN HPT^TM, HA, and PN HPT^TM + HA were tested at various concentrations over multiple time points. Our results demonstrated that all tested treatments significantly lowered ROS levels compared to the untreated control. Notably, the PN HPT^TM -based compounds exhibited robust scavenging activity, with PN HPT^TM + HA displaying the strongest and most consistent ROS-neutralizing effect across all concentrations and time points. This enhanced performance suggests a synergistic interaction between PN HPT^TM and HA, potentially due to complementary mechanisms of free radical scavenging and structural stabilization. These findings highlight the potential of PN HPT^TM and PN HPT^TM + HA as effective antioxidative agents, offering potential for therapeutic applications where oxidative stress is central, including wound healing and tissue regeneration.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172439","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":"Silibinin Alleviates Liver Oxidative Stress in D-Galactose-Treated Kunming Mice via Microbiota Homeostasis in a Microbiota-Dependent Manner.","authors":"Ao Dong, Xianglong Zhang, Jianxiang Ma, Jiahui Cao, Gnagna Diene, Yiou Xu, Xiujie Yin, Yang Li, Yonggen Zhang","doi":"10.3390/antiox14091087","DOIUrl":"10.3390/antiox14091087","url":null,"abstract":"<p><p>Hepatic oxidative stress is a key driver in liver injury pathogenesis, with D-galactose (D-gal) modeling serving as an established inducer of accelerated oxidative damage. Silibinin (SLB), a flavonolignan from milk thistle, shows therapeutic promise through potent antioxidant activity and gut-liver axis modulation. This study investigated whether the hepatoprotective effect of SLB against oxidative stress depends on gut microbiota regulation. Using mouse models with gut microbiota ablation by oral antibiotics or direct oxidative stress induction by D-gal (150 mg/kg), SLB treatment (200 mg/kg) was administered. The protective mechanisms were evaluated through the Nrf2/ARE pathway, target gene expression, gut microbiota profiling, and cecal metabolomics. Results demonstrated that SLB significantly alleviated D-gal-induced hepatic oxidative stress (e.g., reduced MDA by 33.3%), but this protection was markedly weakened after antibiotic-induced microbiota depletion (e.g., a loss of efficacy exceeding 50%). Integrated omics revealed that antibiotics caused a severe reduction in unclassified_Muribaculaceae (a butyrate producer, decreased by 80%), impairing butyrate-mediated Nrf2/Keap1 activation. Simultaneously, the absence of Parabacteroides led to accumulated primary bile acids and inhibited secondary bile acid production (e.g., taurochenodeoxycholate reduced by 75%), further disrupting redox homeostasis. Conclusion: Silibinin's mitigation of hepatic oxidative stress is gut microbiota-dependent, highlighting the therapeutic potential of microbiota-targeted antioxidant strategies for oxidative stress-related pathologies.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172608","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":"Hydrogen Sulfide Deficiency Contributes to Tubular Damage and Calcium Oxalate Crystal Formation in Hyperoxaluria Nephropathy: Role of Osteopontin and Tamm-Horsfall Protein.","authors":"Chien-Lin Lu, Yi-Shiou Tseng, Wen-Bin Wu, Chun-Hou Liao, Ming-Chieh Ma","doi":"10.3390/antiox14091088","DOIUrl":"10.3390/antiox14091088","url":null,"abstract":"<p><p>Hydrogen sulfide (H₂S) exerts regulatory functions in kidney diseases. However, its protective role against kidney stone formation remains unclear. Here, we demonstrate that hyperoxaluria or oxalate exposure impairs H₂S formation, leading to tubular injury and calcium oxalate (CaOx) crystal deposition in both in vivo and in vitro models. In male rats fed 5% hydroxy-L-proline (HP), time-dependent increases in urinary supersaturation, tubular damage, and renal CaOx deposition were observed compared to controls. These changes were associated with the decreased expression of H₂S-producing enzymes and elevated urinary secretion of osteopontin (OPN) and Tamm-Horsfall protein (THP). Notably, the protein level and activity of specificity protein 1 (Sp1), a transcription factor regulating these enzymes, were markedly decreased in HP-treated kidneys. Chronic supplementation with the H₂S donor GYY4137 (GYY) significantly attenuated HP-induced tubular injury and CaOx deposition by reducing OPN and THP secretion. Consistent with in vivo results, H₂S donors mitigated oxalate-induced tubular cell damage and CaOx formation in MDCK cells. Mechanistically, oxalate activated cyclic AMP/protein kinase A (PKA) signaling, which promoted OPN and THP secretion; these effects were eradicated by the PKA inhibitor H89 or GYY. These findings indicate that hyperoxaluria impairs Sp1 transcriptional activity, resulting in H₂S deficiency and compromised anticrystallization defense in oxalate-induced tubulopathy.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172513","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":"Antioxidant Potential of Pollen Polyphenols in Mitigating Environmental Stress in Honeybees (<i>Apis mellifera</i>).","authors":"Ivana Tlak Gajger, Aleksandar Cvetkovikj","doi":"10.3390/antiox14091086","DOIUrl":"10.3390/antiox14091086","url":null,"abstract":"<p><p>Honeybee populations are increasingly threatened by various environmental stressors, including pesticides, pathogens, and climate change. Emerging research highlights the vital role of pollen polyphenols in supporting honeybee health through a network of antioxidants, immune responses, and detoxification mechanisms. This review synthesizes current findings on the chemical diversity, bioactivity, and functional relevance of polyphenolic compounds in honeybee nutrition. Pollen polyphenols, which include flavonoids and phenolic acids, possess remarkably high antioxidant potential, up to 235 times greater than that of nectar. They also significantly increase the expression of antioxidant enzymes, immune system genes, and detoxification pathways such as cytochrome P450s and glutathione-S-transferases. These compounds also demonstrate antimicrobial effects against key pathogens and mitigate the toxic effects of pesticides. The content and composition of polyphenols vary seasonally and geographically, impacting the resilience of honeybee colonies. Field and laboratory studies confirm that polyphenol-rich diets improve survival, gland development, and stress resistance. Advanced analytical techniques, including metabolomics, have expanded our understanding of polyphenol profiles and their effects on honeybee physiology. However, knowledge gaps remain in pharmacokinetics and structure-function relationships. Integrating this evidence into conservation strategies and good beekeeping practices, such as habitat diversification and targeted feed supplementation, is crucial for maintaining honeybee health and ecosystem services in a rapidly changing environment.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172361","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":"A Genome-Wide Association Study Reveals QTLs and Candidate Genes Associated with the Carotenoid Content in the Flesh of <i>Cucurbita pepo</i> L. Fruit.","authors":"Alba López, Alicia García, Alejandro Castro-Cegrí, María Segura, Álvaro Benítez, Francisco Palma, Dolores Garrido, Cecilia Martínez, Manuel Jamilena","doi":"10.3390/antiox14091090","DOIUrl":"10.3390/antiox14091090","url":null,"abstract":"<p><p>Considering the importance of carotenoids in the human diet, their enhancement is a key trait in current breeding programs. This study assessed lutein, zeaxanthin, α-carotene, and β-carotene levels in the flesh of mature fruits from 257 global <i>C. pepo</i> accessions. Lutein and β-carotene were the most prevalent, with top accessions identified for each carotenoid. A panel of 120 accessions with reliable carotenoid contents and genetic diversity was analyzed using 23,111 GBS-generated SNPs in genome-wide association studies (GWAS). Three genomic regions (<i>qtl1, qtl3,</i> and <i>qtl13</i>) on chromosomes 1, 3, and 13 were significantly linked to carotenoid levels, with alternative alleles increasing the carotenoid content, leading to yellowish-orange flesh. Seven candidate genes were identified: <i>CpTIC56</i>, <i>CpHSHP70</i>, and <i>CpPDL8</i>, which regulate carotenoid biosynthesis in chloroplasts; <i>CpSPX</i> and <i>CpPHO1</i>, associated with phosphate homeostasis and carotenoid buildup; <i>CpMYB106</i>, co-expressed with carotenoid biosynthesis genes; and a <i>CpPPR</i> RNA-binding protein. RNA-seq data from yellow- and white-fleshed fruits supported their involvement in carotenoid accumulation. These results improve our understanding of the genetic control of carotenoid buildup in <i>C. pepo</i> fruit, supporting breeding efforts for improved nutritional quality.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172363","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":"Oxidative Stress-Mediated DNA Damage Induced by Ionizing Radiation in Modern Computed Tomography: Evidence for Antioxidant-Based Radioprotective Strategies.","authors":"Baltasar Ramos, Jorge Gómez-Cayupán, Isidora Aranis, Esperanza García Tapia, Constanza Coghlan, María-José Ulloa, Santiago Gelerstein Claro, Katherine Urbina, Gonzalo Espinoza, José De Grazia, Jorge Díaz, Prisco Piscitelli, Daniel Castro, Marcia Manterola, Ramón Rodrigo, Camilo G Sotomayor","doi":"10.3390/antiox14091085","DOIUrl":"10.3390/antiox14091085","url":null,"abstract":"<p><p>Computed tomography (CT) is fundamental to modern medicine, yet ionizing radiation (IR) exposure causes DNA damage. Although often underestimated, at current doses, CT may account for ~5% of new cancer diagnoses. Complementary radioprotective approaches beyond dose reduction are needed. We conducted a prospective observational study to characterize IR-induced oxidative stress (OS)-mediated DNA damage in modern CT to explore potential antioxidant-based radioprotective strategies. In volunteers not exposed to IR (A_NONE) and in patients with two-phase abdominal-pelvis CT (B_EXPOSURE), blood samples were collected at T_BASE-min 0 and T_POST-min 60 to measure biomarkers of OS (oxidative damage and antioxidant capacity) and DNA damage. Thirty-five subjects (<i>n</i> = 17 A_NONE/18 B_EXPOSURE) were studied. Body mass index and DNA damage in T_BASE were comparable between groups. In A_NONE, biomarkers of OS and DNA damage did not change between T_BASE and T_POST (<i>p</i> > 0.05 for all). In B_EXPOSURE, DNA damage was significantly increased [15% (-15-60); <i>p</i> < 0.001], which was associated with consistent increased antioxidant enzyme activity [<i>p</i> < 0.05 for all antioxidant enzymes]. In modern CT with relatively low effective dose (ED) levels, a significant increase in DNA damage was observed along with increased antioxidant enzyme activity as defensive response and marker of OS-mediated damage-mediating mechanisms. These findings warrant interventional studies to evaluate antioxidant-based radioprotective strategies.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172310","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}