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Cultured mouse neuroblastoma cells exhibit a striking increase in antioxidative capacity during the transition from logarithmically dividing cells to nondividing, neurite-bearing cells. Two physically separable phenomena are involved: (a) the membrane pellet of neurite-bearing cells is highly resistant to lipid peroxidation, and (b) the postmicrosomal supernatant of these cells inhibits peroxidation in rat liver mitochondria and other biological membranes. A precise, single-phase assay has been developed for assessing antioxidant levels in lipid extracts. By means of this assay, the increase in membrane resistance to lipid peroxidation has been correlated with a threefold increase in the antioxidant activity of the neuroblastoma neutral lipid fraction. This finding implies that generations of a neutral lipid antioxidant (or antioxidants) is involved in the profound increase in antioxidative capacity which occurs in differentiating neuroblastoma cells.
The content of 5'-methylcytosine in total DNA of mouse liver increases 2--2,5-fold 3 hrs after a single intraperitoneal injection of antioxidant (4-methyl-2,6-ditretbutylphenol) (20 or 60 mg per 1 kg of body weight) and makes up to 2--2.4 mol.%. The methylation of liver DNA is also increased more than 2-fold in Ehrlich ascite carcinoma. The DNA isolated from mouse liver after administration of antioxidant or during cancer growth markedly differs from liver DNA of intact animals in its CH3-accepting ability under in vitro methylation by the methylase complex from Enterobacter cloacea. The changes in DNA methylation in mouse liver under the effects of antioxidant and in Ehrlich ascite carcinoma are correlated with the changes in the antioxidant activity of liver nuclear lipids.
The generation of an antioxidant has been shown to be associated with the dramatic increase in resistance to lipid peroxidation which occurs during the differentiation of mouse neuroblastoma cells in culture. The antioxidant has been isolated from the neuroblastoma neutral lipid fraction and partially characterized by means of low-resolution and high-resolution mass spectrometry and other lines of evidence. All presently available information suggests that this antioxidant is a highly aromatic, monosubstituted phenol having the molecular formula C19H14O2.
Changes in the antioxidative activity (AOA) of the liver were studied during natural aging in noninbred and C3HA mice and during administration of the synthetic anti-oxidant 2-ethyl-6-methyl-3-hydroxypyridine hydroxypyridine hydrochloride to the animals, and the effect of the doses of this compound on the level of AOA in the liver of animals aged 2 months also was investigated. Liver AOA in mice was found to decrease during aging; the decreae in animals with tumors was found to be two or three times slower than in animals without tumors. Administration of the compound after the age of 8 months led to a considerable increase in liver AOA, and this may evidently account for the considerable lengthening of the life of the experimental animals.
Increasing concentrations of malonaldehyde and beta-propiolactone were increasingly mutagenic with 7 mutants of Salmonella typhimurium, 5 of which mutated bya frameshift mechanism and 2 of which mutated through base-pair substitution. The antioxidants vitamin C, vitamin E, selenium and butylated hydroxytoluene (BHT) at 3 logarithmic concentrations markedly reduced mutagenesis in those strains which mutated by frameshift mechanism.
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BACKGROUND: The antioxidant potential of citrus plants is closely related to their geographical origin, making it crucial to evaluate the natural antioxidant properties of Citrus medica L. (C. medica) from Medog County, Tibet. METHODS: This study systematically investigates the antioxidant mechanisms of C. medica using network pharmacology, molecular docking, and experimental assays. RESULTS: The antioxidant activity experiments showed that C. medica exhibits good bioactivity, and the fruit has better antioxidant activity than the leaves. Network pharmacology revealed 11 active components of C. medica with 1547 antioxidant-related targets. Key targets include TP53, IL6, AKT1, STAT3, and TNF. Gene ontology (GO) analysis identified 1419 biological process entries, 147 cellular component entries, and 306 molecular function entries. Kyoto Encyclopedia of Genes and Genomes analysis identified 212 antioxidant-related signaling pathways. The GO and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the targets are involved in cancer pathways, protein binding, enzyme binding, lipid metabolism, and atherosclerosis. Molecular docking demonstrated that the 11 active components of Medog C. medica exhibit binding energies with core targets TP53, IL6, AKT1, STAT3, and TNF generally less than -5 kcal·mol-1, indicating good affinity. CONCLUSION: This study identifies the excellent antioxidant activity of C. medica from multiple aspects and elucidates its potential antioxidant mechanisms, providing a theoretical basis for the development and application of C. medica as an antioxidant functional additive.
AIMS: The antioxidant defense system of Mycobacterium tuberculosis is critical for pathogenicity and persistence within macrophages, yet the regulatory networks remain poorly understood. This study aims to elucidate the molecular mechanism by which the transcription factor CasR regulates antioxidant defense in mycobacteria through delineation of the regulatory axis linking CasR activity, target gene expression, and the antioxidant phenotype. METHODS AND RESULTS: Using Mycobacterium smegmatis as a model organism, we demonstrate that overexpression of CasR renders the bacteria significantly susceptible to hydrogen peroxide. Electrophoretic mobility shift assay (EMSA) and β-galactosidase reporter analyses reveal that CasR directly binds and represses the promoter of cyp144, an uncharacterized cytochrome P450-encoding gene. Deletion of casRMsmreduces biofilm formation, consistent with the expected derepression of cyp144Msm, a gene that negatively regulates both biofilm and oxidative stress tolerance. EMSA and β-galactosidase activity assays also demonstrate that CasR negatively regulates antioxidant gene katGI, suggesting that CasR exerts a broader, global regulatory role within the mycobacterial antioxidant defense network. Furthermore, we identify isoleucine 18 as a critical residue for the DNA-binding and regulatory function of CasR. CONCLUSION: This study establishes CasR as a pleiotropic transcriptional regulator that directly controls multiple antioxidant genes, including cyp144 and katGI, in mycobacteria. We report a previously unrecognized role for a cytochrome P450 family member in suppressing bacterial antioxidant capacity, as cyp144 overexpression reduces biofilm formation. These findings provide a valuable reference for further investigation into mycobacterial antioxidant mechanisms and identify CasR and Cyp144 as potential targets for the development of anti-tuberculosis drugs.
Alterations of lipid antioxidative activity in liver and tumor as well as change in weight of spleen and tumor were studied in mice with hepatoma-22 after administration of synthetic antioxidant 4-methyl-2,6-ditertbutylphenol (ionol) at doses 30 mg/kg and 100 mg/kg during the 6th day of growth of the tumor. Lipid antioxidative activity was shown to respond similarly to administration of ionol in liver tissue of both the intact and tumor-bearing animals. The antioxidative activity was increased after administration of these doses of the antioxidant, then the antioxidative activity was decreased down to the initial level when the dose 30 mg/kg was used and below this level--at the dose 100 mg/kg. Both doses of the drug increased the lipid antioxidative activity in tumor. The dose 30 mg/kg of ionol stimulated the growth of the tumor and increased the weight of spleen in tumor-bearing animals and the dose 100 mg/kg--inhibited these parameters. Regulation of oxidation of the lipids in tumor appears to be impaired or altered to another level as compared with the oxidation of lipids in normal tissues or in the tissues of tumor-bearing animals.
Antioxidants increase the number of mitoses in epithelial cell populations being on differentiation, examined from various parts of small intestinal crypts of mice. 2 hours after antioxidant injection a considerable increase in mitotic index (MI) is found, with maximal value (by 3 times) seen for cells from higher crypt region where more differentiated cells occur. The increase of MI is observed also in later period, 14, 21--24 hours after antioxidant administration. The observed effect may be explained by the influence of antioxidants on the reserve pool of cells. However, it does not seem unlikely that the increase of MI after antioxidant injection may be due to the influence of antioxidants on the longevity of individual stages of mitotic cycle. Similar evidence was provided earlier by the authors for the effect of antioxidants on the mitotic division of liver cells of normal mice.
Leaves of Paeonia lactiflora are underutilized by-products with potential as natural antioxidant sources. In this study, 18 cultivars were evaluated for phytochemical composition and in vitro antioxidant capacity. Total phenolic content correlated strongly with DPPH and ABTS activities, and the comprehensive antioxidant index identified 'Coral Charm' and 'Hangshao' as representative high- and low-antioxidant cultivars, respectively. Untargeted metabolomics detected 2677 metabolites and identified 908 differential metabolites between the two cultivars. Targeted phenolic profiling quantified 27 compounds, among which 11 differed significantly between the two cultivars. Catechin and epicatechin were enriched in 'Coral Charm', with contents of 6.62 and 0.397 ng/mg, respectively, compared with 0.012 and 0.002 ng/mg in 'Hangshao'. (+)-Dihydroquercetin was also more abundant in 'Coral Charm', while caffeic acid showed an upward trend. Proteomic analysis identified 423 differentially expressed proteins, mainly associated with secondary metabolite biosynthesis, redox homeostasis, and central carbon metabolism. Integrated analysis identified pyruvate metabolism as the only pathway significantly enriched in both metabolomic and proteomic datasets. Molecular docking predicted favorable binding between representative phenolics and selected proteins. These findings link cultivar-dependent antioxidant variation in peony leaves with free-phenolic accumulation and pathway-level metabolic differences, supporting the selection and utilization of antioxidant-rich peony leaf resources.
A yellow autofluorescent pigment, generally thought to be indicative of membrane autoxidation, was found to accumulate in the retinal pigment epithelium (RPE) of rats maintained for 32 weeks on diets producing physiological antioxidant deficiency. The largest build-up of fluorescent pigment occurred in rats fed a diet high in polyunsaturated fatty acids (PUFAs) and deficient in alpha-tocopherol (vitamin E), selenium, sulfur-containing amino acids, and chromium. These latter four nutrients have all been implicated in maintaining the antioxidant status of tissues, whereas PUFAs are pro-oxidants. Dietary supplementation with methionine and chromium significantly reduced the amount of fluorescent pigment accumulated in the RPE. Supplementation with all four nutrients further reduced the amount of fluorescent pigment to a very low level. Rats maintained on a normal laboratory diet, relatively low in PUFAs and presumably adequate in other nutrients, accumulated relatively small amounts of fluorescent pigment in the RPE. Of all tissues in the retina and choroid, the autofluorescent pigment was found to be almost entirely restricted to the RPE. The autofluorescence produced in the RPE by antioxidant deficiency was more concentrated than that produced in the testes, kidney, intestine, and heart. This suggests that the RPE is particularly sensitive to physiological antioxidant deficiencies. The increased fluorescent pigment build-up in the RPE of antioxidant-deficient rats appears to correlate with a decreased RPE melanin content. Similar changes in pigmentation have been reported to occur in human RPE with age and in dominantly inherited retinitis pigmentosa. Thus, with respect to its effect on RPE pigmentation, antioxidant deficiency appears to mimic aging and possibly some aspects of one type of retinitis pigmentosa.
The argan tree (Argania spinosa) is an endemic Moroccan species known for its primary product, argan oil, which possesses exceptional nutritional and medicinal properties. The current study aimed to evaluate and compare the antidiabetic and antioxidant activities of argan oil obtained from the introduced and native argan tree in eastern Morocco, to analyze its chemical composition using HPLC-DAD and GC-MS, and to investigate the molecular mechanisms behind the obtained pharmacological activities through an in silico pharmacological networking and molecular docking study. The results revealed that argan oil from all three regions of Morocco (Oujda, Agadir, and Chouihya) is rich in oleic and linoleic acids as major constituents, along with the presence of significant tocopherols. Regarding the antioxidant assays, including DPPH radical scavenging and iron-reducing power tests, argan oil from Oujda exhibited the highest activity, with the lowest IC50 values of 15.25 ± 0.022 mg/mL and 28.5 ± 1.7 mg/mL, respectively. Concerning the antidiabetic activity, we found that oil from Chaouihya showed the strongest α-amylase inhibition, while Oujda oil had the highest antiglycation activity, indicating that even introduced argan trees retain potent bioactivity. The results of the in silico investigation suggested that tocopherols may contribute to the antioxidant and antidiabetic potential of argan oil, showing predicted antioxidant activity (Pa = 0.843-0.967) and favorable binding affinities toward iNOS (ΔG = -9.3 kcal mol-1) and α-glucosidase (ΔG = -8.2 kcal mol-1). The identified fatty acids also showed predicted insulin-promoting activity (Pa = 0.59-0.75) and moderate enzyme-binding potential. Pharmacological network analysis identified 51 shared genes associated with antioxidant, antidiabetic, and argan-related targets, with enrichment of the AGE-RAGE signaling pathway. These computational findings provide possible molecular associations that may help explain the observed biological activities, although they remain predictive and require experimental validation. Overall, the in silico analysis suggests that tocopherols could be among the contributors to the multi-target profile of Argania spinosa oil, while fatty acids may provide complementary effects related to glycemic regulation.
Ability of tocoferols to react with free radicals (constant K7) is determined by means of chemoluminescent method. A succession of activities is obtained for tocoferol homologues; this succession coincides with that of their biological activity. The products of oxidative transformations of tocoferols are shown to posess an inhibiting activity. Formation of sufficiently active free radicals is a characteristic feature of the antioxidative action of tocoferols. The extremal dependence of the antioxidative activity of tocoferols on their concentration is explained by the participation of these radicals in the reactions of the continuation of the oxidation chain. According to their kinetic characteristics tocoferols fall into the category of weak antioxidants. Peculiarities of the antioxidative effect of tocoferols help to explain their high biological activity. Since tocoferols have high enough values of the constants K7, even slight changes in their concentration in lipids will essentially affect the rate of oxidative processes. This peculiarity makes them rather unique, since they are first spent in the oxidation reactions proceeding in lipids, and they can be substituted only by the substances which have the constants K7 of the same order. The specificity of antioxidative properties of tocoferols enables their efficient control over peroxide oxidation of lipids.
High-fat diets (HFDs) are widely used in aquaculture to improve growth and feed efficiency; however, prolonged feeding can disrupt lipid metabolism, induce oxidative stress, and impair physiological homeostasis. This study evaluated the protective effects of dietary naringenin against HFD-induced physiological alterations in the marine medaka Oryzias dancena. Fish were randomly assigned to one of four dietary treatments and fed the respective experimental diets for 45 days: a normal-fat diet (NFD, 8% crude lipid), a high-fat diet (HFD, 15% crude lipid), or an HFD supplemented with either 0.075% or 0.15% naringenin. Compared with the NFD group, HFD feeding impaired antioxidant status, altered the expression of genes associated with antioxidant defence and lipid metabolism, and promoted hepatic lipid accumulation. Dietary naringenin, particularly at 0.15%, mitigated these adverse effects by restoring muscle superoxide dismutase activity, enhancing total antioxidant capacity, reducing lipid peroxidation, partially normalizing the expression of lipid metabolism-related genes, and alleviating hepatic lipid vacuolation. These findings indicate that dietary naringenin improves antioxidant defence and helps maintain lipid metabolic homeostasis under high-fat feeding conditions, highlighting its potential as a functional dietary additive for aquaculture.
Flavonoids are key bioactive compounds in plants with significant health benefits. This study employs an integrated multi-omics approach to investigate flavonoid diversity and antioxidant capacity across three Isatis species: I. oblongata, I. tinctoria, and I. indigotica. Metabolomic profiling identified 200 flavonoids, with glycosides being the most abundant class. I. tinctoria exhibited the highest total flavonoid content and antioxidant activity, strongly correlated with the accumulation of 53 core differential flavonoid metabolites, most of which were glycosylated derivatives. Transcriptomic analysis revealed coordinated upregulation of phenylpropanoid pathway genes and specific UDP-glycosyltransferases (UGTs) in I. tinctoria, providing a genetic basis for its enhanced glycoside production. The study establishes a clear genotype-metabolite-phenotype linkage, highlighting glycosylation as a key mechanism underlying flavonoid-driven antioxidant superiority in Isatis. Although the current evidence is primarily correlative, the consistent and strong associations across independent transcriptomic, metabolomic, and antioxidant datasets provide a robust foundation for this conclusion. These findings offer new insights into the metabolic evolution and regulatory networks of flavonoids, with implications for breeding and metabolic engineering of high-value medicinal plants.