Free Radical Research最新文献

Endothelial dysfunction is a risk factor for atherosclerosis and includes impaired endothelium-dependent vasodilatation. We have shown previously that low density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Macrophage lysis in atherosclerotic lesions might expose endothelial cells to this oxidized LDL and adversely affect their function. LDL was oxidized by ferrous sulfate (5 µM) for 24 h at pH 4.5 at 37 °C. Aortas from male Wistar rats were cut into rings and subjected to wire myography for isometric tension recording. The rings were incubated with or without oxidized LDL (50 µg protein/ml) for one hour, constricted with 100 nM phenylephrine and relaxation to acetylcholine (1 nM - 3 µM) was measured. There was about 50% less relaxation in the presence of this oxidized LDL. Endothelial-independent vasodilatation induced by sodium nitroprusside was less affected by oxidized LDL. Oxidized LDL increased the formation of reactive oxygen species by the aortic rings and by cultured human aortic and dermal microvascular endothelial cells, which might have inactivated nitric oxide. Acetylcholine increased the activatory phosphorylation of eNOS (ser-1177), but oxidized LDL had little effect on this activation in cultured human aortic endothelial cells. These findings raise the possibility that LDL oxidized in lysosomes and released from lysed macrophages might decrease vasodilatation in atherosclerotic arteries.

Hypochlorous acid HOCl is an effective disinfectant with a broad spectrum and high rate of microbicidal action. Its use for air treatment can be an effective tool for the prevention and therapy of infectious diseases. In this work, the in vivo study was conducted on 110 Wistar Han rats (12 and 72 weeks old) on the effect of a single inhalation of air containing gaseous HOCl on the activity of antioxidant system enzymes. For this, a special installation was designed to uniformly maintain the concentration of HOCl in the air and regulate it over a wide range. Inhalation exposure was carried out for 4 h at total chlorine concentrations in the air of approximately 2.0 mg/m³ and 5.0 mg/m³, after which the animals were observed for 14 days. The effect of inhalation on the antioxidant system activity varied significantly in animals of different ages. Catalase activity in young rats increased approximately 2-fold on days 1-2 after inhalation, regardless of the HOCl concentration, while in old animals a sharp dose-dependent decrease was initially observed. The glutathione peroxidase activity in animals of both ages increased upon inhalation of air with 5.0 mg/m³ HOCl, and in old animals this was more pronounced; when the HOCl concentration decreased to 2.0 mg/m³, this indicator increased slightly in old rats and remained virtually unchanged in young ones. The glutathione reductase activity when exposed to 2.0 mg/m³ HOCl did not change for both age groups, and with increasing HOCl concentration it increased by 1.5-2.0 times in all animals.

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.

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, in vivo 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 in vivo 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, in silico 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.

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 (^•OH) were (1.6 ± 0.3) × 10¹⁰, (9.0 ± 0.9) × 10⁹, (1.4 ± 0.3) × 10⁹, (1.8 ± 0.1) × 10¹⁰, and (1.0 ± 0.1) × 10¹⁰ M^-1s^-1, respectively, indicating that formation of peptide bond can affect the reaction of amino acids with ^•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) × 10⁸, (2.3 ± 0.1) × 10⁸, and (3.3 ± 0.4) × 10⁸ M^-1s^-1, respectively, implying that the presence of a positive charge may enhance the chemical repair process.

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.

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.

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.

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.