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Journal of Orthopaedic Science :... Sep 2022We aimed to compare biochemical and histopathological findings of astaxanthin's potential effects on oxidative stress in ischemia/reperfusion damage (I/R).
BACKGROUND
We aimed to compare biochemical and histopathological findings of astaxanthin's potential effects on oxidative stress in ischemia/reperfusion damage (I/R).
METHODS
Thirty-two rats were randomly divided into four groups: control group; I/R group; I/R + treatment group; drug group. Astaxanthin was orally administered to groups C and D for 14 days. In groups B and C, the femoral artery was clamped for 2 h to form ischemia. The clamp was opened, and reperfusion was performed for 1 h. In all groups, 4 ml of blood sample through intracardiac puncture and gastrocnemius muscle tissue samples were collected. Serum and tissue samples were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), and total oxidative level (TOL). Necrosis, inflammation, and caspase-3 in muscle tissue collected for histopathological examination were evaluated.
RESULTS
Tissue MDA, SOD and TOL values significantly differed between groups. Serum MDA, SOD, TOL and TAC values significantly differed between groups. On necrosis examination, there was a significant difference between groups B and C. Although signs of inflammation significantly differed between groups, there was no significant difference between groups A and C and groups A and D. Although there was a significant difference in caspase-3 results between groups, there was no significant difference between groups A and C.
CONCLUSIONS
The use of astaxanthin before and after surgery showed preventive or therapeutic effects against I/R damage.
Topics: Animals; Antioxidants; Caspase 3; Inflammation; Necrosis; Oxidative Stress; Rats; Reperfusion Injury; Superoxide Dismutase; Xanthophylls
PubMed: 34384658
DOI: 10.1016/j.jos.2021.05.014 -
The Journal of Biological Chemistry Mar 2018This 11th Thematic Metals in Biology Thematic Series deals with copper, a transition metal with a prominent role in biochemistry. Copper is a very versatile element, and... (Review)
Review
This 11th Thematic Metals in Biology Thematic Series deals with copper, a transition metal with a prominent role in biochemistry. Copper is a very versatile element, and both deficiencies and excesses can be problematic. The five Minireviews in this series deal with several aspects of copper homeostasis in microorganisms and mammals and the role of this metal in two enzymes, copper-only superoxide dismutase and cytochrome oxidase.
Topics: Animals; Copper; Electron Transport Complex IV; Humans; Superoxide Dismutase
PubMed: 29425098
DOI: 10.1074/jbc.TM118.002255 -
Biological Trace Element Research May 2023The study was conducted to assess nano zinc (ZnN) as a feed supplement with an aim to compare the supplemental dose of inorganic zinc (ZnI). ZnN was synthesized from...
The study was conducted to assess nano zinc (ZnN) as a feed supplement with an aim to compare the supplemental dose of inorganic zinc (ZnI). ZnN was synthesized from 0.45 molar (M) zinc nitrate [Zn(NO).6HO] and 0.9 M sodium hydroxide (NaOH) and was confirmed to be of ZnN by TEM-EDAX measurements. Wister albino rats (rats; 84, 53.6 ± 0.65 g) were divided into seven groups (4 replicate with 3 rats each) and given feed supplemented with zinc for 60 days with either of the following diets: (1) normal control (NC): basal diet (BD) + no supplemental Zn; (2) ZnI-25: BD + 25 mg/kg Zn from inorganic ZnO; (3) ZnN-25: BD + 25 mg/kg of ZnN; (4) ZnN-12.5: BD + 12.5 mg/kg of ZnN; (5) ZnN-6.25: BD + 6.25 mg/kg of ZnN; (6) ZnN-3.125: BD + 3.125 mg/kg of ZnN; (7) ZnN-50: BD + 50 mg/kg of ZnN. T and insulin-like growth factor-1 (IGF-1) hormone levels were similar among groups (P > 0.05), whereas T and testosterone were significantly affected, based on supplemented dose. Zn supplementation improved both cell-mediated and humoral immunity. However, both cell-mediated immunity at 24 h and humoral immunity were statistically similar in ZnI-25 and ZnN-6.25 groups. Superoxide dismutase 1 gene expression was found to be similar in all experimental groups. The vascular degeneration were found in liver tissues moderately in NC, mildly in ZnN-6.25 and ZnN-3.125 groups, and no observable changes were noticed in kidney and spleen tissues. However, there was a mild damage in intestinal epithelium of ZnN-25 group rats, hyperplasia of goblet cells, and moderate damage in intestinal villi were observed in ZnN-50 group rats. From the study, it can be concluded that ZnN at half the dose of ZnI showed similar or better responses in terms of immunity, SOD-1 expression, hormonal profiles, and the tissue architecture of vital organs in rats, i.e., 25 mg/kg of Zn from ZnI and 12.5 mg/kg of ZnN impacted similar biological responses like immunity, SOD-1 expression, hormonal profiles, and the tissue architecture of vital organs in rats.
Topics: Animals; Rats; Zinc; Superoxide Dismutase-1; Rats, Wistar; Dietary Supplements; Gene Expression; Liver; Superoxide Dismutase; Diet
PubMed: 35876946
DOI: 10.1007/s12011-022-03355-8 -
Bioorganic Chemistry May 2019A novel copper, zinc superoxide dismutase (CuZnSOD) was purified to homogeneity from the liver of an animal well adapted to the stressful living conditions of the...
Purification and biochemical characterization of a novel copper, zinc superoxide dismutase from liver of camel (Camelus dromedarius): An antioxidant enzyme with unique properties.
A novel copper, zinc superoxide dismutase (CuZnSOD) was purified to homogeneity from the liver of an animal well adapted to the stressful living conditions of the desert, the camel (Camelus dromedarius). The biochemical properties of camel liver CuZnSOD were examined. The purified enzyme had a native molecular weight of 28 kDa, as judged by gel filtration chromatography, and showed a single band at 27 kDa on SDS-PAGE, indicating that it is a monomeric protein. Optimal activity of the purified enzyme occurred at 43 °C and pH 6.0, and the activation energy was 1.42 kJ/mol. CuZnSOD activity was strongly inhibited by β-ME, DTT, HO and SDS and slightly inhibited by EDTA, NaN and PMSF. Al, Ca, Cd, Mg and Zn stimulated CuZnSOD activity, whereas Ba, Co, Fe and Ni inhibited it. The purified enzyme contained 0.010 µg of Cu and 0.69 µg of Zn per mg of protein. K, V, k and k/K values for NBT and riboflavin were 16.27 and 0.16 µM, 20.85 and 21.54 U/mg, 9.65 and 9.97 s, and 0.59 and 62.33 s µM, respectively. Camel liver CuZnSOD exhibited unique biochemical properties compared to those of other CuZnSODs, including lower molecular weight with a monomeric structure, higher optimum temperature, very low E, very low optimum pH, very low contents of Cu and Zn, and higher affinity, turnover number and catalytic efficiency for riboflavin. These unique properties of camel liver CuZnSOD might be related to the ability of this animal to inhabit stressful desert conditions.
Topics: Animals; Antioxidants; Camelus; Copper; Dose-Response Relationship, Drug; Kinetics; Liver; Molecular Structure; Structure-Activity Relationship; Superoxide Dismutase; Zinc
PubMed: 30771689
DOI: 10.1016/j.bioorg.2019.02.024 -
International Journal of Biological... Nov 2020Superoxide dismutases (SODs) are the first line of defense against oxidative damage caused by reactive oxygen species and are associated with stress tolerance....
Superoxide dismutases (SODs) are the first line of defense against oxidative damage caused by reactive oxygen species and are associated with stress tolerance. Accordingly, many studies have focused on SODs, especially those from extreme habitats. In this study, we reported a novel Cu,Zn-SOD from the new species Benthodytes marianensis sp. nov (hereafter denoted as Bm-Cu,Zn-SOD) collected from the Mariana Trench. The purified recombinant enzyme with an approx. Mr. of 38 kDa was intracellular and dimeric, and it expressed activity at an optimal temperature of 30 °C and optimum pH of 7.4. The Km and Vmax values of Bm-Cu,Zn-SOD were 0.046 ± 0.004 mM and 1209.151 ± 24.057 U/mg, respectively. Under the tested conditions, Bm-Cu,Zn-SOD resisted interference from chemicals (β-mercaptoethanol and ethylenediaminetetraacetic acid), denaturants (urea and guanidine hydrochloride), and high salinity, showing high kinetic stability. Furthermore, Bm-Cu,Zn-SOD could be activated by high hydrostatic pressure. All these properties suggested adaptation to the deep-sea environment and thus indicated its potential future applications.
Topics: Animals; Cloning, Molecular; Kinetics; Phylogeny; Salinity; Sea Cucumbers; Sequence Alignment; Superoxide Dismutase; Temperature
PubMed: 32971171
DOI: 10.1016/j.ijbiomac.2020.09.135 -
Journal of Inorganic Biochemistry Jun 2020Encapsulation of three superoxide dismutase (SOD) functional mimics, [CuZn(dien)(μ-Im)(ClO)]ClO (1), [Cu(dien)(μ-Im)(ClO)]ClO (2) (Im = imidazolate,...
Encapsulation of three superoxide dismutase (SOD) functional mimics, [CuZn(dien)(μ-Im)(ClO)]ClO (1), [Cu(dien)(μ-Im)(ClO)]ClO (2) (Im = imidazolate, dien = diethylenetriamine), and [CuZn(salpn)Cl] (3) (Hsalpn = 1,3-bis(salicylideneamino)propane) in mesoporous MCM-41 silica afforded three hybrid catalysts 1@MCM-41, 2@MCM-41 and 3@MCM-41. Spectroscopic and magnetic analyses of these materials confirmed the metal centers of the complexes keep the coordination sphere after insertion into the MCM-41 silica matrix. For the imidazolate-bridged complexes the silica channels restraint the relative orientation of the two metal ions. While 3@MCM-41 shows SOD activity significantly lower than the host-free complex, insertion of the imidazolate-bridged CuZn or Cu complexes by ion exchange onto mesoporous MCM-41 silica affords durable and recoverable supported catalysts with much better SOD activity than the free complexes. For confined imidazolate-bridged complexes, 1@MCM-41 and 2@MCM-41, the small pore size of the silica matrix improves the SOD activity more than a host with larger pores. This high SOD activity is attributed to the close-fitting of the complexes into the nanochannels of MCM-41 silica that favors the Cu active site and HImZn(or Cu) group stay in close proximity during catalysis.
Topics: Catalysis; Copper; Electron Spin Resonance Spectroscopy; Imidazoles; Organometallic Compounds; Silicon Dioxide; Spectrophotometry, Ultraviolet; Superoxide Dismutase; Zinc
PubMed: 32163801
DOI: 10.1016/j.jinorgbio.2020.111050 -
Biochemistry. Biokhimiia May 2016Superoxide dismutases (SODs) are key enzymes functioning as the first line of antioxidant defense by virtue of the ability to convert highly reactive superoxide radicals... (Review)
Review
Superoxide dismutases (SODs) are key enzymes functioning as the first line of antioxidant defense by virtue of the ability to convert highly reactive superoxide radicals to hydrogen peroxide and molecular oxygen. SOD plays a central role in protecting plants against the toxic effects of reactive oxygen species generated during normal cellular metabolic activity or as a result of various environmental stresses. Our review focuses on the characteristics of expression of SOD genes, the mechanisms regulating expression of SOD genes at transcriptional, posttranscriptional, and translation levels, and their functional role(s) during development and in response to biotic or abiotic stresses. We propose two important research directions: studying SOD at the genome-wide or proteome-wide level, and improving plant stress tolerances by selecting varieties using transgenic technology.
Topics: Gene Expression Regulation, Plant; MicroRNAs; Plant Proteins; Plants; RNA Precursors; Reactive Oxygen Species; Stress, Physiological; Superoxide Dismutase; Temperature
PubMed: 27297897
DOI: 10.1134/S0006297916050047 -
Acta Neuropathologica Jan 2023Mutations in the gene encoding the ubiquitously expressed free radical scavenging enzyme superoxide dismutase-1 (SOD1) are found in 2-6% of amyotrophic lateral sclerosis...
Mutations in the gene encoding the ubiquitously expressed free radical scavenging enzyme superoxide dismutase-1 (SOD1) are found in 2-6% of amyotrophic lateral sclerosis patients. The most frequent SOD1 mutation worldwide is D90A. Amyotrophic lateral sclerosis caused by this mutation has some unusual features: the heredity is usually recessive, the phenotype is stereotypic with slowly evolving motor symptoms beginning in the legs and may also include sensory, autonomic, and urinary bladder involvement. Furthermore, the mutant protein resembles the wild type, with normal content and enzymatic activity in the central nervous system. Here, we report neuropathological findings in nine patients homozygous for the D90A mutation. All nine had numerous small granular inclusions immunoreactive for misfolded SOD1 in motor neurons and glial nuclei in the spinal cord and brainstem. In addition to degeneration of the corticospinal tracts, all patients had degeneration of the dorsal columns. We also found intense gliosis in circumscribed cortical areas of the frontal and temporal lobes and in the insula. In these areas and in adjacent white matter, there were SOD1 staining neuropil threads. A few SOD1-immunopositive cytoplasmic neuronal inclusions were observed in cortical areas, as were glial nuclear inclusions. As suggested by the symptoms and signs and earlier neurophysiological and imaging investigations, the histopathology in patients homozygous for the D90A SOD1 extends beyond the motor system to include cognitive and sensory cortical areas. However, even in the patients that had a symptomatic disease duration of more than 2 or 3 decades and lived into their 70s or 80s, there were no SOD1-inclusion pathology and no typical dysfunction (apart from the musculature) in non-nervous organs. Thus, only specific parts of the CNS seem to be vulnerable to toxicity provoked by homozygously expressed mutant SOD1.
Topics: Humans; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Superoxide Dismutase; Central Nervous System; Motor Neurons; Mutation; Pyramidal Tracts
PubMed: 36385230
DOI: 10.1007/s00401-022-02519-z -
Journal of Proteomics Feb 2023Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease, and the pathogenic mechanism that underlies ALS is still unclear. We analyzed the...
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease, and the pathogenic mechanism that underlies ALS is still unclear. We analyzed the differentially expressed proteins (DEPs) in the spinal cord between SOD1-G93A transgenic mice at the onset stage and non-transgenic (NTG) littermates based on 4D label-free quantitative proteomics (4D-LFQ) with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, 189 DEPs were screened, of which 166 were up-regulated and 23 down-regulated. Clusters of Orthologous Groups (COG)/ EuKaryotic Orthologous Groups (KOG) classification, subcellular localization annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, clustering analysis and protein-protein interaction (PPI) network analyses were performed. Parallel reaction monitoring (PRM) analysis validated 48 proteins from immunity and inflammation-related pathways of KEGG. We described the function and distribution of DEPs, most of which were involved in the following pathways: complement and coagulation cascades, antigen processing and presentation, NF-kappa B signaling pathway, Retinoic acid-inducible gene I (RIG) -I-like receptor signaling pathway, the extracellular matrix-receptor (ECM-receptor) interaction, focal adhesion, phagosome and lysosome. PPI network analysis identified Fn1, Fga, Serpina1e and Serpina3n as potential biomarkers. Our discoveries broaden the view and expand our understanding of immunity and inflammation in ALS. SIGNIFICANCE: This study gives a comprehensive description of DEPs in the spinal cord proteomics of SOD1-G93A mice at the onset period. Compared with a previous study focusing on progressive stage, we showed that immunity and inflammation play an important role at the onset stage of ALS. Several pathways validated by PRM bring new insight to the pathological mechanisms of ALS. The participation of RIG-I-like signaling pathway in ALS and potential biomarkers Fga, Fn1, Serpina1e and Serpina3n are supplements to existing knowledge.
Topics: Mice; Animals; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Proteomics; Chromatography, Liquid; Tandem Mass Spectrometry; Mice, Transgenic; Spinal Cord; Inflammation; Disease Models, Animal; Superoxide Dismutase
PubMed: 36423857
DOI: 10.1016/j.jprot.2022.104776 -
ACS Chemical Neuroscience Jul 2023Amyotrophic lateral sclerosis (ALS) is believed to be caused by the aggregation of misfolded or mutated superoxide dismutase 1 (SOD1). As there is currently no...
Amyotrophic lateral sclerosis (ALS) is believed to be caused by the aggregation of misfolded or mutated superoxide dismutase 1 (SOD1). As there is currently no treatment, research into aggregation inhibitors continues. Based on docking, molecular dynamics (MD) simulations, and experimental observations, we propose that myricetin, a plant flavonoid, can act as a potent anti-amyloidogenic polyphenol against SOD1 aggregation. Our MD simulation results showed that myricetin stabilizes the protein interface, destabilizes the preformed fibril, and decreases the rate of fibril elongation. Myricetin inhibits the aggregation of SOD1 in a dose-dependent manner as shown by the ThT aggregation kinetics curves. Our transmission electron microscopy, dynamic light scattering, and circular dichroism experiments indicate that fewer shorter fibrils have formed. Fluorescence spectroscopy results predict the involvement of a static quenching mechanism characterized by a strong binding between protein and myricetin. Importantly, size exclusion chromatography revealed the potential of myricetin for fibril destabilization and depolymerization. These experimental observations complement the MD results. Thus, myricetin is a potent SOD1 aggregation inhibitor that can reduce the fibril load. Using the structure of myricetin as a reference, it is possible to design more effective therapeutic inhibitors against ALS that prevent the disease and reverse its effects.
Topics: Humans; Superoxide Dismutase-1; Amyotrophic Lateral Sclerosis; Polyphenols; Flavonoids; Superoxide Dismutase; Mutation
PubMed: 37314311
DOI: 10.1021/acschemneuro.3c00276