Free Radical ResearchPub Date : 2024-08-01Epub Date: 2024-08-22DOI: 10.1080/10715762.2024.2394121
Raktim Nath, Alaiha Zaheen, Sanchaita Rajkhowa, Rahul Kar
{"title":"Polyphenolic metacyclophane as a radical scavenger for therapeutic activation: a computational study.","authors":"Raktim Nath, Alaiha Zaheen, Sanchaita Rajkhowa, Rahul Kar","doi":"10.1080/10715762.2024.2394121","DOIUrl":"10.1080/10715762.2024.2394121","url":null,"abstract":"<p><p>Modeling antioxidants for improved human health is a prime area of research. Inclusion complexes exhibit antioxidant activity. Supramolecular scaffolds like calixtyrosol are anticipated to have considerable antioxidant and therapeutic activity. In this study, we have designed 30 polyphenolic metacyclophanes and investigated their antioxidant properties. Exceptional O─H bond dissociation energy of 44 kcal/mol is reported for a metacyclophane with acyl urea linkage. This may be explained through a cooperative effect of localization of spin density distribution and an intramolecular hydrogen bonding of the corresponding radical. Further, the pharmacokinetics and toxicity analysis screened eight drug-like candidates. The interaction of the eight screened molecules with the Lysozyme transport protein and SOD protein has been studied using the molecular docking approach. Lastly, the MD simulations are performed to analyze the conformational changes of the transport protein after complexation with the proposed molecules. Comprehensive analyses including density functional studies of physiological parameters, favorable pharmacokinetics, toxicity, molecular docking, and MD simulations affirmed polyphenolic metacyclophane XXI as a radical scavenging and drug-like candidate.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reduction of oxidative damage in prostate tissue caused by radiation and/or chloroquine by apocynin.","authors":"Onur Ertik, Ayca Sezen Us, Ilknur Bugan Gul, Huseyin Us, Melis Coremen, Omur Karabulut Bulan, Refiye Yanardag","doi":"10.1080/10715762.2024.2393147","DOIUrl":"10.1080/10715762.2024.2393147","url":null,"abstract":"<p><p>Prostate damage can occur in men due to age and genetic factors, especially when exposed to external factors. Radiation (RAD) is a prominent factor leading to oxidative stress and potential prostate damage. Additionally, chloroquine (CQ), used in malaria treatment, can induce oxidative stress in a dose-dependent manner. Therefore, reducing and preventing oxidative damage in prostate tissue caused by external factors is crucial. Rats used in the study were divided into seven groups, CQ, apocynin (APO), RAD, CQ + APO, CQ + RAD, APO + RAD, CQ + APO + RAD. Subsequently, <i>in vivo</i> biochemical parameters of prostate tissues were examined, including reduced glutathione, lipid peroxidation, superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase activities, and total antioxidant status, total oxidant status, reactive oxygen species, oxidative stress index, advanced oxidation protein products and histologically. The <i>in vivo</i> results presented in our study showed that APO reduced oxidative stress and had a protective effect on prostate tissue in the CQ, RAD, and CQ + RAD groups as a results of biochemical and histological experiments. Additionally, <i>in silico</i> studies revealed a higher binding affinity of diapocynin to target proteins compared to APO. As a histological results, RAD and CQ alone or in combination did not induce damage in prostate tissues, whereas mild histopathological findings such as hyperemia and haemorrhage were observed in all APO-treated groups. The results suggest that the use of APO for the treatment of oxidative damage induced by CQ and RAD in rats.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanushree Das, Sanchaita Mondal, Sujata Das, Sanjib Das, Krishna Das Saha
{"title":"Enhanced anticancer activity of (-)-epigallocatechin-3-gallate (EGCG) encapsulated NPs toward colon cancer cell lines.","authors":"Tanushree Das, Sanchaita Mondal, Sujata Das, Sanjib Das, Krishna Das Saha","doi":"10.1080/10715762.2024.2360013","DOIUrl":"10.1080/10715762.2024.2360013","url":null,"abstract":"<p><p>(-)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol of green tea, has chemo-preventive effects against various cancer cells. Nanoparticles (NPs) carrying different ligands are able to specifically interact with their receptors on different cancer cells that can provide effective release of cytotoxic drugs. In the present study, we have prepared EGCG entrapped NPs using PLGA (poly(d,l-lactide-co-glycolide)). Polyethylene glycol (PEG) and folic acid (FA) via double emulsion solvent evaporation (DESE) method obtained PLGA-EGCG (P-E), PLGA-PEG-EGCG (PP-E), and PLGA-PEG-FA-EGCG (PPF-E). Nanoformulations had been characterized with <sup>1</sup>H NMR and FT-IR techniques, AFM, and DLS. PPF-E NPs showed an average size of 220 nm. Analysis of zeta potential confirmed the stability of NPs. HCT-116, HT-29, HCT-15, and HEK 293 cells were treated with both the prepared NPs and free EGCG (0-140 μM). Result showed PPF-E NPs had improved delivery, uptake and cell cytotoxicity toward human folic acid receptor-positive (FR+) colorectal cancer (CRC) cells as mainly on HCT-116 compared to HT-29, but not on the folic acid-negative cells (FR-) as HCT-15. PPF-E NPs enhanced intracellular reactive oxygen species (ROS) level in absence of N-acetyl-l-cysteine (NAC), elevated DNA fragmentation level, and increased apoptotic cell death at higher doses compared to other two NPs and free EGCG. In conclusion, PPF-E NPs exerted greater efficacy than PP-E, P-E, and free EGCG in HCT-116 cells.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydroxyl radical scavenging and chemical repair capabilities of positively charged peptides (PCPs): a pulse radiolysis study.","authors":"Chaozhong Tian, Shinichi Yamashita, Atsushi Kimura, Yui Obata, Hao Yu, Mitsumasa Taguchi","doi":"10.1080/10715762.2024.2385342","DOIUrl":"10.1080/10715762.2024.2385342","url":null,"abstract":"<p><p>Pulse radiolysis was employed to investigate fundamental radiation chemical reactions, which are essential in the radiation protection of DNA. Two positively charged peptides (PCPs), histidine-tyrosine-histidine (His-Tyr-His) and lysine-tyrosine-lysine (Lys-Tyr-Lys), as well as the amino acids that constitute them, were involved. The reaction rate constants for tyrosine (Tyr), histidine (His), lysine (Lys), His-Tyr-His, and Lys-Tyr-Lys with OH radicals (<sup>•</sup>OH) were (1.6 ± 0.3) × 10<sup>10</sup>, (9.0 ± 0.9) × 10<sup>9</sup>, (1.4 ± 0.3) × 10<sup>9</sup>, (1.8 ± 0.1) × 10<sup>10</sup>, and (1.0 ± 0.1) × 10<sup>10</sup> M<i><sup>-</sup></i><sup>1</sup>s<i><sup>-</sup></i><sup>1</sup>, respectively, indicating that formation of peptide bond can affect the reaction of amino acids with <sup>•</sup>OH. Observed transient absorption spectra indicated a shielding effect of the His or Lys residues at both ends of the PCPs on the centrally located Tyr. The measurement of chemical repair capabilities using deoxyguanosine monophosphate (dGMP) as a model for DNA demonstrated that the reaction rate constants of Tyr, His-Tyr-His, and Lys-Tyr-Lys with dGMP radicals were (2.2 ± 0.5) × 10<sup>8</sup>, (2.3 ± 0.1) × 10<sup>8</sup>, and (3.3 ± 0.4) × 10<sup>8</sup> M<i><sup>-</sup></i><sup>1</sup>s<i><sup>-</sup></i><sup>1</sup>, respectively, implying that the presence of a positive charge may enhance the chemical repair process.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-05-01Epub Date: 2024-06-04DOI: 10.1080/10715762.2024.2360015
Rurong Mao, Li Li, Penghao Li
{"title":"Unveiling an oxidative stress-linked diagnostic signature and molecular subtypes in preeclampsia: novel insights into pathogenesis.","authors":"Rurong Mao, Li Li, Penghao Li","doi":"10.1080/10715762.2024.2360015","DOIUrl":"10.1080/10715762.2024.2360015","url":null,"abstract":"<p><p>Preeclampsia (PE) is a complex pregnancy disorder characterized by hypertension and organ dysfunction, affecting both maternal and fetal health. Oxidative stress has been implicated in the pathogenesis of PE, but the underlying molecular mechanisms remain poorly understood. In this study, we aimed to identify a diagnostic signature and molecular subtypes associated with oxidative stress in PE to gain novel insights into its pathogenesis. The ssGSEA algorithm evaluated oxidative stress-related pathway scores using transcriptional data from the GSE75010 dataset. Oxidative stress-related genes (ORGs) were co lected from these pathways, and hub ORGs associated with PE were identified using the LASSO and logistic regression models. A nomogram prediction model was constructed using the identified ORGs. Consensus clustering identified two molecular subgroups related to oxidative stress, labeled as C1 and C2, with unique immune characteristics and inflammatory pathway profiles. Seventy ORGs associated with oxidative stress, ce l death, and inflammation-related pathways were identified in PE. EGFR, RIPK3, and ALAD were confirmed as core ORGs for PE biomarkers. The C1 and C2 subgroups exhibited distinct immune characteristics and inflammatory pathway profiles. This study provides novel insights into the role of oxidative stress in PE pathogenesis. A diagnostic signature and molecular subtypes associated with oxidative stress were identified, which may improve understanding, diagnosis, and management of PE.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-05-01Epub Date: 2024-07-31DOI: 10.1080/10715762.2024.2386075
Shanshan Guo, Zexin Li, Yi Liu, Ying Cheng, Degong Jia
{"title":"Ferroptosis: a new target for hepatic ischemia-reperfusion injury?","authors":"Shanshan Guo, Zexin Li, Yi Liu, Ying Cheng, Degong Jia","doi":"10.1080/10715762.2024.2386075","DOIUrl":"10.1080/10715762.2024.2386075","url":null,"abstract":"<p><p>Ischemia-reperfusion injury (IRI) can seriously affect graft survival and prognosis and is an unavoidable event during liver transplantation. Ferroptosis is a novel iron-dependent form of cell death characterized by iron accumulation and overwhelming lipid peroxidation; it differs morphologically, genetically, and biochemically from other well-known cell death types (autophagy, necrosis, and apoptosis). Accumulating evidence has shown that ferroptosis is involved in the pathogenesis of hepatic IRI, and targeting ferroptosis may be a promising therapeutic approach. Here, we review the pathways and phenomena involved in ferroptosis, explore the associations and implications of ferroptosis and hepatic IRI, and discuss possible strategies for modulating ferroptosis to alleviate the hepatic IRI.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-05-01Epub Date: 2024-08-05DOI: 10.1080/10715762.2024.2385338
Andrey A Buglak
{"title":"Antioxidant properties of α-amino acids: a density functional theory viewpoint.","authors":"Andrey A Buglak","doi":"10.1080/10715762.2024.2385338","DOIUrl":"10.1080/10715762.2024.2385338","url":null,"abstract":"<p><p>The antioxidant properties of 21 proteinogenic amino acids (AAs) and 3,4-dioxophenylanine (DOPA) have been studied in implicit water using density functional theory (DFT). All the calculations have been performed according to three oxidation mechanisms: (1) hydrogen-atom transfer (HAT); (2) single electron transfer followed by proton transfer (SET-PT); and (3) sequential proton-loss electron transfer (SPLET). As a result, five AAs with the highest antioxidant capacity have been established: DOPA, selenocysteine (Sec), tyrosine (Tyr), cysteine (Cys), and tryptophan (Trp). Also, global reactivity in terms of hardness/softness has been evaluated, as well as Fukui indices of local reactivity. Trp has been determined as the most reactive molecule, whereas selenium atom of Sec has been established as the most reactive atom. All the findings are in agreement with the recent literature on both experimental and theoretical studies of amino acids antioxidant activity. However, to the best of my knowledge, the calculations for one electron redox reactions of zwitterionic amino acids in implicit water have been performed for the first time.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-05-01Epub Date: 2024-08-07DOI: 10.1080/10715762.2024.2386457
Hui Xiang, Miao Wang, Yi-Fang Chen, Hao-Ming Wu, Ming-Ge Li, Lei Guo, Ying-Yi Zhang, He-Zhe Lu
{"title":"Regulation of cancer cell ferroptosis by PTRF/Cavin-1.","authors":"Hui Xiang, Miao Wang, Yi-Fang Chen, Hao-Ming Wu, Ming-Ge Li, Lei Guo, Ying-Yi Zhang, He-Zhe Lu","doi":"10.1080/10715762.2024.2386457","DOIUrl":"10.1080/10715762.2024.2386457","url":null,"abstract":"<p><p>Ovarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cells to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress, and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-05-01Epub Date: 2024-07-01DOI: 10.1080/10715762.2024.2348789
Lei Xu, Jie Jia, Jingjing Yu, Shudan Miao, Ying Zhang
{"title":"The impact of aerobic exercise timing on BMAL1 protein expression and antioxidant responses in skeletal muscle of mice.","authors":"Lei Xu, Jie Jia, Jingjing Yu, Shudan Miao, Ying Zhang","doi":"10.1080/10715762.2024.2348789","DOIUrl":"10.1080/10715762.2024.2348789","url":null,"abstract":"<p><p>It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}