Free Radical Research最新文献

Non-thermal plasma (NTP) has been reported to exhibit various biological effects, including hemostatic, anticancer, and wound-healing properties. However, the effects of NTP on allergic responses in mast cells and basophils have not been sufficiently investigated. In this study, we examined the effects of NTP on immunoglobulin E-mediated degranulation and cytokine expression in the basophilic cell line RBL-2H3. To induce degranulation and cytokine expression as part of allergic reactions, we treated the cells with 2,4-dinitrophenylated bovine serum albumin after sensitization or with the Ca²⁺ ionophore A23187. Cells were also treated with NTP-activated acetated Ringer's solution (PAA). Degranulation was measured by quantifying the β-hexosaminidase activity. PAA treatment inhibited both antigen stimulation- and A23187-induced degranulation in RBL-2H3 cells, and suppressed antigen-induced mRNA expression of cytokines, including IL-4, IL-6, and TNF-α. Antigen stimulation caused disintegration of the F-actin cytoskeleton, and PAA treatment suppressed these morphological changes. Cotreatment with PAA and catalase blocked the inhibitory effects of PAA on antigen stimulation-induced degranulation. PAA also inhibited A23187-induced extracellular signal-regulated kinase (ERK) phosphorylation and antigen stimulation- or store-operated Ca²⁺ entry inducer thapsigargin-induced cellular Ca²⁺ influx. These results indicate that PAA effectively inhibits immunological responses in allergic cells-such as degranulation and cytokine expression-by suppressing ERK phosphorylation and Ca²⁺ influx. These findings suggest that PAA may be an effective therapeutic option for treating patients with allergic diseases.

Hydrogen peroxide and peroxynitrite play important roles as signaling molecules to maintain the biological functions; however, excess levels of these oxidants are associated with various diseases. Despite their important roles in vivo, effective methods to measure these oxidants in the body with high sensitivity have not yet been established. Therefore, in this study, we aimed to design a radioiodinated boronic acid probe for the in vivo detection of hydrogen peroxide and peroxynitrite. The probe contained boronic acid, a well-known substructure that reacts with hydrogen peroxide and peroxynitrite, at positions 3 and 6 of the xanthene moiety and radioiodine at the phthalide moiety of fluorescein. I-125 labeling was successful, resulting in a radiochemical yield of 60% and radiochemical purity of >95%. In vitro selectivity studies demonstrated that the probe showed significant responses to both hydrogen peroxide and peroxynitrite while exhibiting minimal reactivity toward other reactive oxygen species including superoxide, nitric oxide, and peroxy radicals. In biodistribution studies using lipopolysaccharide (LPS)-treated mice generating reactive oxidants, the boronic acid probe was significantly accumulated in various organs damaged by LPS. However, this phenomenon was inhibited by administration of the antioxidant, N-acetylcysteine, to LPS-treated mice. These results highlight the potential of the developed radioiodinated boronic acid probe to detect hydrogen peroxide and peroxynitrite in living organisms, suggesting it as a candidate for the in vivo detection and functional evaluation of these oxidants in various diseases.

With lung cancer rates climbing steadily, the development of effective prevention strategies has become more crucial than ever. Our previous research has revealed that ginger oil possesses potential lung cancer preventive activity, demonstrating inhibitory effects against tobacco carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice. 6-Gingerol, a bioactive compound from ginger (Zingiber officinale Rosc.), exhibits multiple pharmacological activities. However, the preventive efficacy of 6-Gingerol against tobacco carcinogen-induced lung cancer remains unclear. This study investigated the chemopreventive effects of 6-Gingerol on NNK-induced lung tumorigenesis in A/J mice and Beas-2b cells. Results indicated that 6-Gingerol significantly reduced lung tumor count and improved tissue structure compared to NNK alone. In vitro, 6-Gingerol protected Beas-2b cells from NNK-induced damage. Mechanistically, 6-Gingerol activated the Nrf2 pathway, enhancing antioxidant enzyme expression and reducing oxidative stress. Additionally, 6-Gingerol exhibited anti-inflammatory effects by inhibiting the NNK-activated TLR4/NF-κB pathway. In conclusion, 6-Gingerol shows significant chemopreventive effects against NNK-induced lung cancer via activating Nrf2 and suppressing TLR4/NF-κB, underscoring its potential as a preventive agent functional food in lung cancer development.

This study provides a comprehensive assessment of the antioxidant potential of Asphodelus tenuifolius Cav. From El-Oued region of southeastern Algeria, through a combined spectrophotometric, electrochemical, and chromatographic approach. A hydroethanolic crude extract was fractionated using solvents of increasing polarity (chloroform, ethyl acetate, and n-butanol). HPLC profiling identified and quantified nine major phenolic compounds, with quercetin dominating the chloroform fraction at exceptionally high levels alongside significant amounts of chlorogenic acid and naringin. Antioxidant capacity was evaluated using complementary assays. The chloroform fraction exhibited the highest total phenolic content and flavonoid content, correlating with its potent radical scavenging activity in the DPPH assay. In contrast, electrochemical analysis revealed that the ethyl acetate fraction was most effective against the superoxide anion (O₂•^-), with the lowest IC₅₀ value. Thermodynamic parameters further confirmed spontaneous and energetically favorable interactions between extract constituents and O₂•^- radicals, underscoring the mechanistic plausibility of the observed effects. To the best of our knowledge, this work delivers the first integrated electrochemical and chromatographic evidence of the antioxidant potential of A. tenuifolius extracts. By establishing clear correlations between phytochemical composition and functional outcomes, the study positions this species as a promising source of high-value bioactive compounds for several applications.

Breast cancer (BC) is among the most prevalent malignant tumors affecting women, with a persistently high mortality rate. Reactive oxygen species (ROS) significantly contribute to BC progression by damaging cellular components and activating oncogenic signaling pathways. Peroxiredoxins (Prdxs), a crucial class of antioxidant enzymes, regulate cellular redox homeostasis and play dual roles in cancer development and progression. Substantial progress has been achieved in studying Prdxs in cancers such as cervical cancer, squamous cell carcinoma, and lung cancer; however, a comprehensive understanding of roles for Prdxs in BC remains lacking. This paper reviews the differential expression and functional characteristics of Prdxs across various molecular subtypes of BC, with a particular focus on triple-negative BC. Moreover, aberrant Prdxs expression is strongly associated with poor prognosis, chemoresistance, and increased invasiveness in BC patients. Given the pivotal roles of Prdxs in BC, investigating therapeutic strategies targeting Prdxs and related ROS levels is imperative. Additionally, combining such approaches with immunotherapy highlights the potential implication of Prdxs in precision cancer therapy.

Nano-theranostics using biodegradable polymers are effective for the diagnosis and treatment of intractable cancers; however, there is a need for technology that controls bioavailability and biodegradability without compromising biocompatibility. In this study, peptide nanoparticles (NPs) with controlled particle size and biodegradability were prepared by ionizing radiation and loaded with imaging agents and anticancer drugs to develop novel nano-theranostics for pancreatic cancer diagnosis and treatment. Peptides composed of histidine, glycine, glutamic acid, and an arginine-glycine-aspartic acid motif were synthesized by the solid-phase synthesis method. Their aqueous solutions were irradiated with γ-rays to produce NPs with a particle size of less than 50 nm, enabling penetration of the pancreatic cancer stroma. The radiation crosslinking of peptides, with or without the arginine-glycine-aspartic acid motif, in water was investigated by pulse radiolysis. Peptide NPs loaded with fluorescent labeling or magnetic resonance imaging (MRI) agents were efficiently taken up by pancreatic cancer cells. Cisplatin-loaded peptide NPs produced by higher-dose irradiation suppress drug-release rates owing to their lower biodegradability. In conclusion, peptide NPs with controllable particle size and biodegradability were produced by ionizing radiation and loaded with fluorescent labeling agents, MRI agents, and anticancer drugs to develop a new nano-theranostics drug for pancreatic cancer diagnosis and treatment.

Introduction: Oxidative stress is implicated in various diseases, and the NADPH oxidase enzyme complex (NOX) is a significant source of reactive oxygen species (ROS). Research linking genetic polymorphisms to enzyme activity has produced conflicting results. Methods: We aimed to establish a robust protocol to assess NOX activity in vitro under highly standardized conditions and correlate these measurements with genetic polymorphisms catalogued by the 1000 Human Genome Project and the HapMap Project. Lymphoblastoid cell lines (LCLs) served as a model system with samples from healthy participants from three Caucasian populations. NOX activity stimulated by phorbol 12-myristate 13-acetate was measured using chemiluminescence in 290 LCLs (198 in a training and 92 in a test set) through a series of multiply repeated measurements per LCL comprising in total over 1,500 NOX activity assessments. The association between NOX activity and single nucleotide polymorphisms (SNPs) in the NOX subunit genes CYBA, CYBB, NCF1, NCF2, and NCF4 was subsequently examined. Results: Out of 651 valid polymorphic markers, 308 had a minor allele frequency of ≥ 5%, and 15 SNPs showed a statistically significant correlation with NOX activity in the training set. However, these 15 associations were not confirmed in the test set (all p ≥ 0.1). Additional analyses treating all 290 LCLs as a single cohort yielded three associations at p < 0.01, i.e. CYBA rs1017828, NCF1 rs191081238, and NCF4 rs4821544. However, statistical significance could not be called for any of these genetic markers upon adjustment for multiple testing, regardless whether a co-dominant, dominant or recessive allelic effect was assumed. Conclusion: Our results do not support a reproducible impact of common genetic diversity in NOX subunits on the enzyme activity in LCLs of subjects of Caucasian origin. This study represents the largest evaluation concerning relationships between NOX genetic variants and enzyme activity to date.

Despite the potential of drug-radiotherapy combinations, a limited number of oncology drugs are approved by FDA for use along with radiotherapy. Currently, there is no agent available in the clinic that can exhibit dual radiomodifying behavior. Despite availability of sophisticated, high-precision techniques in radiotherapy for accurate targeting of tumors, normal tissue toxicity impedes its use in curative settings. Combining radiotherapy with an agent that can protect normal tissue and augment tumor killing can improve therapy outcomes. Other than combining drugs for therapeutic radiation exposure, there is a pressing need of identifying agents for management of unwanted effects of accidental radiation exposure. There is a serious deficit in the repertoire of currently available safe and effective radiation countermeasures. Baicalein, a bioactive component from the roots of traditional Chinese medicinal herb Scutellaria baicalensis has been shown to protect against acute as well as chronic effects of radiation exposure including normal tissue injury to lungs, gut, hematopoietic system, intestine, endothelial and neuronal cells by us and other labs worldwide. Further, administration of baicalein alone or in combination with other agents prevents radiation-induced mortality in mice. Additionally, numerous studies have reported radiosensitizing potential of baicalein in lung, breast, esophageal, cervical and prostate cancer. Moreover, safety, tolerability, and pharmacokinetics of baicalein is well established in healthy human subjects. Here we provide a succinct overview of the distinctive radiomodifying potential of baicalein, safety, pharmacology underscoring its utility as a prospective radiomodifier in clinical settings.

DNA damage arises not only from the direct action of ionizing radiation but also from indirect action mediated by highly reactive hydroxyl radicals (^•OH). This study aimed to determine whether the protective or sensitizing effects of amino acids against X-ray-induced DNA damage are associated with the side-chain characteristics of these amino acids. Seven amino acids with distinct side-chain properties were investigated. The rate constants for their reactions with ^•OH were determined by electron pulse radiolysis. Highly purified, scavenger-free plasmid DNA (pUC18) was irradiated with X-rays in the presence of each amino acid, whose concentrations were adjusted to scavenge ∼14% of ^•OH. DNA strand breaks (SSBs and DSBs) were quantified by agarose gel electrophoresis. At the same time, oxidative base lesions and apurinic/apyrimidinic (AP) sites were detected as enzyme-sensitive sites (ESSs) using formamidopyrimidine-DNA glycosylase (Fpg), endonuclease III (Nth), and endonuclease IV (Nfo). Despite equivalent ^•OH scavenging capacities, the extent and spectrum of DNA damage varied markedly among the amino acids. Aspartic acid (Asp) and phenylalanine (Phe) exhibited the strongest overall protection, while glycine (Gly) showed the weakest protection, even with partial sensitization. Amino acids with highly hydrophilic or hydrophobic side chains tended to exhibit more substantial protective effects, although a clear correlation was not always observed for molecular weight or isoelectric point. Side-chain properties and potential chemical repair mechanisms are likely to contribute to the modulation of DNA damage. This work provides new mechanistic insights into amino acid-mediated DNA radioprotection, suggesting promising directions for molecular-level studies of amino-acid-DNA interactions.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases that affect the central nervous system (CNS) in elderly individuals. As of right now, there is no recognized cure for this illness. Bioactive phytochemicals are a natural alternative that can help older persons postpone age-related cognitive diseases. This study attempts to establish whether nicotine, may diminish Parkinsonism in a model of Caenorhabditis elegans disease. This study analyzes the antioxidant and restorative mitochondrial dysfunction potential of nicotine and its related neuroprotective benefits by utilizing models of Caenorhabditis worm strains that are different from the wild type. We examined the effects of nicotine on oxidative stress tolerance and associated regulatory pathways using a model of Caenorhabditis worms. Our results showed that wild-type C. elegans treated with nicotine had higher survival rates during oxidative stress caused by Juglone than those treated with the control. Nicotine decreased intracellular reactive oxygen species levels in C. elegans. In addition, nicotine increased levels of SOD, CAT, and MDA as well as the expression of genes related to stress response, including gst-4, hsf-6, and hsf-1, and mitochondrial function genes, including mev-1, isp-1, and cox-4. Finally, our molecular analysis indicates that the anti-oxidative effects of nicotine are mediated via skin-1 modulation. After Paraquat was administered, nicotine therapy also resulted in higher levels of ATP and MMP. Our research clarifies the various mechanisms of action and communication pathways that underlie nicotine's antioxidant activity in vivo, offering a solid pharmacological foundation for its potential therapeutic use in neurodegeneration.