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Biochimica Et Biophysica Acta. General... Sep 2023Increasing evidence suggests that glaucoma affects the ocular surface. We aimed to investigate the cellular mechanisms underlying the glaucoma-associated corneal...
BACKGROUND
Increasing evidence suggests that glaucoma affects the ocular surface. We aimed to investigate the cellular mechanisms underlying the glaucoma-associated corneal alterations in an animal model.
METHODS
Wistar rats underwent the cauterization of two episcleral veins of the left eye to elevate the intraocular pressure (ipsilateral, G-IL). Control animals received a sham procedure (C-IL). Contralateral eyes did not receive any procedure (G-CL or C-CL). Enzymes related to the redox status, oxidative damage to macromolecules, and inflammatory markers were assessed in corneal lysates.
RESULTS
Compared to C-IL, NOX4, NOX2, and iNOS expression was increased in G-IL (68%, p < 0.01; 247%, p < 0.01; and 200%, p < 0.001, respectively). We found an increase in SOD activity in G-IL (60%, p < 0.05). The GSH/GSSG ratio decreased in G-IL (80%, p < 0.05), with a decrease in GR activity (40%, p < 0.05). G-IL displayed oxidative (90%, p < 0.01) and nitrosative (40%, p < 0.05) protein damage, and enhanced lipid peroxidation (100%, p < 0.01). G-IL group showed an increased in CD45, CD68 and F4/80 expression (50%, p < 0.05; 190%, p < 0.001 and 110%, p < 0.05, respectively). G-CL displayed a higher expression of Nrf2 (60%, p < 0.001) and increased activity of SOD, CAT, and GPx (60%, p < 0.05; 90%, p < 0.01; and 50%, p < 0.05, respectively).
CONCLUSIONS
Glaucoma induces a redox imbalance in the ipsilateral cornea with an adaptive response of the contralateral one.
GENERAL SIGNIFICANCE
Our study provides a possible mechanism involving oxidative stress and inflammation that explains the corneal alterations observed in glaucoma. We demonstrate that these changes extend not only to the ipsilateral but also to the contralateral cornea.
Topics: Rats; Animals; Rats, Wistar; Glaucoma; Oxidative Stress; Oxidation-Reduction; Cornea; Superoxide Dismutase
PubMed: 37451477
DOI: 10.1016/j.bbagen.2023.130426 -
Journal of Aerosol Medicine and... Oct 2023Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of...
Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat induced ARDS. Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in . Purified proteins were evaluated in assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an -induced ARDS rat model. SOD proteins exhibited high SOD activity and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an -induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS.
Topics: Rats; Humans; Animals; Lung Injury; Escherichia coli; Reactive Oxygen Species; Oxidants; Administration, Inhalation; Respiratory Aerosols and Droplets; Superoxide Dismutase; Lung; Respiratory Distress Syndrome; Pneumonia, Bacterial; Cytokines
PubMed: 37638822
DOI: 10.1089/jamp.2022.0069 -
Journal of Chromatography. A Nov 2023In the present study, a comprehensive strategy integrating affinity ultrafiltration high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry...
Rapid screening and identification of superoxide dismutase activators from traditional Chinese medicines based on affinity ultrafiltration mass chromatography combined with molecular docking.
In the present study, a comprehensive strategy integrating affinity ultrafiltration high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UF-HPLC-Q-TOF-MS), in silico molecular docking and bioassays was established to rapidly screen natural SOD activators from traditional Chinese medicines. As illustrative case studies, Schisandra chinensis, Fructus cnidii and Radix ophiopogonis were chosen to develop and verify the strategy. The HPLC-Q-TOF-MS was used to identify the compounds in comparison with reference standards and literature data. A total of eight compounds, including four biphenyl-cyclooctene ligands from Schisandra chinensis and four coumarins from Fructus cnidii, were found to potentially increase SOD activities. No ligands were found in the extract of Radix ophiopogonis. Then, in silico molecular docking was performed to investigate the binding site and binding affinity of the candidates on SOD. Compared to the nonspecific ligands screened from the extract, the specific ligands presented stronger binding affinities. In addition, the activity and kinetic parameters of the SOD-ligand were investigated through an improved pyrogallol autoxidation method. Gomisin J and xanthotoxin showed a stronger ability to increase SOD activities. The present study indicated that combining UF-HPLC-Q-TOF-MS and in silico molecular docking offers a powerful and meaningful tool to rapidly screen SOD activators from traditional Chinese medicines.
Topics: Molecular Docking Simulation; Drugs, Chinese Herbal; Ultrafiltration; Chromatography, High Pressure Liquid; Superoxide Dismutase
PubMed: 37804579
DOI: 10.1016/j.chroma.2023.464408 -
Doklady. Biochemistry and Biophysics Jun 2024Oxidative stress plays a crucial role in the pathogenesis of peripheral artery disease (PAD). This study aimed to investigate the effect of clopidogrel on oxidative...
Oxidative stress plays a crucial role in the pathogenesis of peripheral artery disease (PAD). This study aimed to investigate the effect of clopidogrel on oxidative stress in PAD patients. Seventy subjects were divided into three groups: PAD patients before treatment (B-PAD), PAD patients after treatment with clopidogrel (A-PAD), and healthy controls. Serum levels of superoxide dismutase (SOD), copper (Cu), zinc (Zn), manganese (Mn), and oxidized protein were measured. SOD activities were also determined. The results showed that SOD activities, and SOD specific activities were significantly decreased in PAD patients compared to healthy individuals. After treatment with clopidogrel, SOD activities, and SOD specific activities were continuously decrease in PAD patients. The SOD and oxidized protein concentrations were significantly increased in PAD patients compared to healthy individuals. After treatment with clopidogrel, the oxidized protein concentration was significantly decreased, while SOD concentration was significantly increased in PAD patients. These findings suggest that the treatment by clopidogrel stimulated the production of the enzyme but the ratio of active enzyme remained low. The decrease in oxidized protein can be explained by the treatment having antioxidant efficacy that may have compensated for the deficiency in enzyme activity and led to a decrease in oxidized protein. Additionally, the results of this study provide promising evidence that oxidative stress biomarkers including SOD concentration, T-SOD activity, Mn-SOD activity, and oxidized protein levels have potential utility in the diagnosis and management of PAD.
Topics: Humans; Clopidogrel; Superoxide Dismutase; Peripheral Arterial Disease; Male; Female; Middle Aged; Oxidative Stress; Aged; Platelet Aggregation Inhibitors
PubMed: 38700818
DOI: 10.1134/S1607672924600088 -
Bulletin of Entomological Research Aug 2023(Germar) (Coleoptera: Chrysomelidae) is a major pest of common bean ( L.; Fabales: Fabaceae), and adults can defoliate plants during the whole crop cycle. This study...
(Germar) (Coleoptera: Chrysomelidae) is a major pest of common bean ( L.; Fabales: Fabaceae), and adults can defoliate plants during the whole crop cycle. This study was conducted to evaluate the resistance to in 16 common bean genotypes (14 landraces and 2 cultivars), through three different experiments. In the laboratory, choice and no-choice feeding tests were performed to evaluate the percentage of leaf consumption. In the greenhouse, plant height, numbers of leaves, percentage of injured leaves, percentage of injury per leaf, weight of seeds, and survival were evaluated. Furthermore, trichome density, levels of peroxidase (POD), superoxide dismutase (SOD), and protein content in common bean leaves were assessed. In the laboratory, the genotypes Chumbinho Branco, Dobalde, Manteigado, IPR Tuiuiú, and 90D Mouro were the least consumed by . In the greenhouse, the genotypes Dobalde, Manteigado, and IPR Tuiuiú expressed tolerance to the pest, which was associated with a higher plant height and/or unchanged POD and SOD levels and protein content following insect feeding, and no reduction in seed production. The landrace 90D Mouro exhibited antixenosis and tolerance to , observed as a lower leaf injury, higher trichome density, lower protein contents, higher SOD level and no reduction in seed weight. Overall, we have shown that antixenosis and tolerance can help overcome damages resulting from feeding, with emphasis on four common bean genotypes that may be useful in plant breeding programs aimed at controlling in common bean crops.
Topics: Animals; Coleoptera; Phaseolus; Genotype; Crops, Agricultural; Superoxide Dismutase
PubMed: 37334552
DOI: 10.1017/S0007485323000226 -
Molecular Therapy : the Journal of the... Apr 2024The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve...
The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.
Topics: Mice; Humans; Animals; Cell Differentiation; Superoxide Dismutase; Adipocytes; Mesenchymal Stem Cells
PubMed: 38310354
DOI: 10.1016/j.ymthe.2024.01.031 -
Biomolecules Jul 2023Superoxide dismutase (SOD) is an essential enzyme that eliminates harmful reactive oxygen species (ROS) generating inside living cells. Due to its efficacities, SOD is...
Superoxide dismutase (SOD) is an essential enzyme that eliminates harmful reactive oxygen species (ROS) generating inside living cells. Due to its efficacities, SOD is widely applied in many applications. In this study, the purification of SOD produced from TBRC657 was conducted to obtain the purified SOD that exhibited specific activity of 513.74 U/mg with a purification factor of 10.36-fold. The inhibitory test revealed that the purified SOD was classified as Mn-SOD with an estimated molecular weight of 25 kDa on SDS-PAGE. After investigating the biochemical characterization, the purified SOD exhibited optimal activity under conditions of pH 7.0 and 35 °C, which are suitable for various applications. The stability test showed that the purified SOD rapidly decreased in activity under high temperatures. To overcome this, SOD was successfully immobilized on bacterial cellulose (BC), resulting in enhanced stability under those conditions. The immobilized SOD was investigated for its ability to eliminate ROS in fibroblasts. The results indicated that the immobilized SOD released and retained its function to regulate the ROS level inside the cells. Thus, the immobilized SOD on BC could be a promising candidate for application in many industries that require antioxidant functionality under operating conditions.
Topics: Saccharomyces cerevisiae; Reactive Oxygen Species; Superoxide Dismutase; Oxidative Stress; Fibroblasts
PubMed: 37509191
DOI: 10.3390/biom13071156 -
Oral Diseases Nov 2023Enzymatic antioxidants are the primary line of defense against oxidative and nitrosative stress. However, their involvement in the progression of periodontitis is still...
AIM
Enzymatic antioxidants are the primary line of defense against oxidative and nitrosative stress. However, their involvement in the progression of periodontitis is still not well understood. The study aimed to determine the activity of enzymatic antioxidants in the gingival crevicular fluid (GCF) and saliva of patients with periodontitis.
MATERIALS AND METHODS
The study group of 56 patients with periodontitis (stage III and IV) and 28 healthy controls were involved. The modified plaque index, probing depth, the clinical attachment level, the percentage of sites with bleeding on probing, papilla bleeding index, and maximum value of tooth mobility (Periotest®) were tested. Saliva (stimulated and non-stimulated) and GCF were collected from the participants, and activity of peroxidase, catalase, superoxide dismutase, and glutathione reductase were determined colorimetrically.
RESULTS
Lower activity of peroxidase (p < 0.0001), catalase (p < 0.0001), superoxide dismutase (p = 0.0188), and glutathione reductase (p < 0.0001) was noted in non-stimulated saliva of patients with periodontitis compared to healthy subjects. Peroxidase (p < 0.0001), catalase (p < 0.0001) and superoxide dismutase (p < 0.0001) showed lower activity in stimulated saliva of patients with periodontitis compared to healthy subjects. The peroxidase (p < 0.0029), catalase (p < 0.0001), and glutathione reductase (p = 0.0028) activity in GCF of stage III + IV were significantly higher compared to healthy controls. Superoxide dismutase (p < 0.0001) showed lower activity in GCF of patients with periodontitis.
CONCLUSIONS
The demonstrated decrease in activity of all analyzed enzymatic antioxidants in non-stimulated saliva may result from long-lasting periodontitis and exhaustion of the safeguard mechanism against reactive oxygen species.
Topics: Humans; Antioxidants; Catalase; Gingival Crevicular Fluid; Saliva; Glutathione Reductase; Periodontitis; Superoxide Dismutase
PubMed: 35726388
DOI: 10.1111/odi.14287 -
Genetics Oct 2023Oxidative stress can damage DNA and thereby contribute to genome instability. To avoid an imbalance or overaccumulation of reactive oxygen species (ROS), cells are...
Oxidative stress can damage DNA and thereby contribute to genome instability. To avoid an imbalance or overaccumulation of reactive oxygen species (ROS), cells are equipped with antioxidant enzymes that scavenge excess ROS. Cells lacking the RecQ-family DNA helicase Sgs1, which contributes to homology-dependent DNA break repair and chromosome stability, are known to accumulate ROS, but the origin and consequences of this oxidative stress phenotype are not fully understood. Here, we show that the sgs1 mutant exhibits elevated mitochondrial superoxide, increased mitochondrial mass, and accumulation of recombinogenic DNA lesions that can be suppressed by antioxidants. Increased mitochondrial mass in the sgs1Δ mutant is accompanied by increased mitochondrial branching, which was also inducible in wildtype cells by replication stress. Superoxide dismutase Sod2 genetically interacts with Sgs1 in the suppression of nuclear chromosomal rearrangements under paraquat (PQ)-induced oxidative stress. PQ-induced chromosome rearrangements in the absence of Sod2 are promoted by Rad51 recombinase and the polymerase subunit Pol32. Finally, the dependence of chromosomal rearrangements on the Rev1/Pol ζ mutasome suggests that under oxidative stress successful DNA synthesis during DNA break repair depends on translesion DNA synthesis.
Topics: Antioxidants; DNA; Genomic Instability; Oxidative Stress; Reactive Oxygen Species; RecQ Helicases; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Superoxide Dismutase
PubMed: 37638880
DOI: 10.1093/genetics/iyad147 -
Dalton Transactions (Cambridge, England... Aug 2023Manganese (Mn) is one of the most significant bio-metals that helps the body to form connective tissue, bones, blood clotting factors, and sex hormones. It is necessary... (Review)
Review
Manganese (Mn) is one of the most significant bio-metals that helps the body to form connective tissue, bones, blood clotting factors, and sex hormones. It is necessary for fat and carbohydrate metabolism, calcium absorption, blood sugar regulation, and normal brain and nerve functions. It accelerates the synthesis of proteins, vitamin C, and vitamin B. It is also involved in the catalysis of hematopoiesis, regulation of the endocrine level, and improvement of immune function. Again, Mn metalloenzymes like arginase, glutamine synthetase, phosphoenolpyruvate decarboxylase, and Mn superoxide dismutase (MnSOD) contribute to the metabolism processes and reduce oxidative stress against free radicals. Recent investigations have revealed that synthetic Mn-complexes act as antibacterial and antifungal agents. As a result, chemists and biologists have been actively involved in developing Mn-based drugs for the treatment of various diseases including cancer. Therefore, any therapeutic drugs based on manganese complexes would be invaluable for the treatment of cancer/infectious diseases and could be a better substitute for cisplatin and other related platinum based chemotherapeutic drugs. From this perspective, attempts have been made to discuss the interactions and nuclease activities of Mn(II/III/IV) complexes with DNA through which one can evaluate their therapeutic applications.
Topics: Manganese; Superoxide Dismutase; DNA; Neoplasms
PubMed: 37475585
DOI: 10.1039/d3dt00659j