scholarly journals Superoxide Dismutase 1 Nanoparticles (Nano-SOD1) as a Potential Drug for the Treatment of Inflammatory Eye Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 396
Author(s):  
Alexander N. Vaneev ◽  
Olga A. Kost ◽  
Nikolay L. Eremeev ◽  
Olga V. Beznos ◽  
Anna V. Alova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Reproductive Toxicity ◽  
Clinical Problem ◽  
Eye Diseases ◽  
Therapeutic Modality ◽  
Side Reactions ◽  
Copper Zinc Superoxide Dismutase ◽  
Tissue Degeneration ◽  
Endogenous Antioxidant

Inflammatory eye diseases remain the most common clinical problem in ophthalmology. The secondary processes associated with inflammation, such as overproduction of reactive oxygen species (ROS) and exhaustion of the endogenous antioxidant system, frequently lead to tissue degeneration, vision blurring, and even blindness. Antioxidant enzymes, such as copper–zinc superoxide dismutase (SOD1), could serve as potent scavengers of ROS. However, their delivery into the eye compartments represents a major challenge due to the limited ocular penetration. This work presents a new therapeutic modality specifically formulated for the eye on the basis of multilayer polyion complex nanoparticles of SOD1 (Nano-SOD1), which is characterized by appropriate storage stability and pronounced therapeutic effect without side reactions such as eye irritation; acute, chronic, and reproductive toxicity; allergenicity; immunogenicity; mutagenicity even at high doses. The ability of Nano-SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with a model immunogenic uveitis—the inflammation of the inner vascular tract of the eye. It was shown during preclinical studies that topical instillations of Nano-SOD1 were much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as corneal and conjunctival edema, iris hyperemia, and fibrin clots. Moreover, Nano-SOD1 penetrates into interior eye structures more effectively than SOD itself and retains enzyme activity in the eye for a much longer period of time, decreasing inflammation and restoring antioxidant activity in the eye. Thus, the presented Nano-SOD1 can be considered as a potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.

scholarly journals Induction of Copper-Zinc Superoxide Dismutase in Gerbil Hippocampus after Ischemia

1993 ◽  
Vol 13 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Tomohiro Matsuyama ◽  
Hisamasa Michishita ◽  
Hitoshi Nakamura ◽  
Masato Tsuchiyama ◽  
Souichiro Shimizu ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
In Situ Hybridization ◽  
Control Level ◽  
Antioxidant Defenses ◽  
Hybridization Technique ◽  
Copper Zinc Superoxide Dismutase ◽  
Pyramidal Layer ◽  
Endogenous Antioxidant

To assess the role of Cu-Zn superoxide dismutase (CuZnSOD) in regulating cellular antioxidant defenses, we studied the induction of CuZnSOD mRNA by an in situ hybridization technique and of CuZnSOD protein by an immunocytochemical method in the gerbil hippocampus following 5 min of transient global ischemia. For hybridization, we synthesized 48-mer oligonucleotide (base 465–512) complementary to rat CuZnSOD mRNA. Northern blot analysis showed hybridization to a single band of molecular weight 0.65 kb. After 5 min of ischemia, the signal became stronger at 3 and 24 h and returned to the control level 3 days later. In situ hybridization histochemistry revealed an increase in labeling throughout the hippocampus, especially in the granular layer 3 h following ischemia. The increase was prolonged only in the CA1 pyramidal layer after 24 h and was eliminated within 3 days or later. Conversely, analysis by Western blotting revealed that the insult produced few effects on the induction of CuZnSOD protein. Immunocytochemistry for CuZnSOD revealed a reduced immunostaining in the CA1 pyramidal layer at 24 h of recirculation when the persistent expression of CuZnSOD mRNA was shown in the same area. Our findings suggest that the expression of endogenous CuZnSOD is temporarily stimulated by an ischemic insult without increasing the protein level. The prolonged increase in mRNA and the decrease in the protein of CuZnSOD in the CA, neurons seem to imply an important role of the endogenous antioxidant enzyme that protects against the detrimental effects of superoxide radicals on delayed neuronal death.

scholarly journals A Superoxide Dismutase C Mutant of Haemophilus ducreyi Is Virulent in Human Volunteers

2002 ◽  
Vol 70 (3) ◽  
pp. 1367-1371 ◽  
Author(s):  
Cliffton T. H. Bong ◽  
Kate R. Fortney ◽  
Barry P. Katz ◽  
Antoinette F. Hood ◽  
Lani R. San Mateo ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Haemophilus Ducreyi ◽  
Swine Model ◽  
Bacterial Survival ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Human Volunteers ◽  
Significant Difference ◽  
Copper Zinc

ABSTRACT Haemophilus ducreyi produces a periplasmic copper-zinc superoxide dismutase (Cu-Zn SOD), which is thought to protect the organism from exogenous reactive oxygen species generated by neutrophils during an inflammatory response. We had previously identified the gene, sodC, responsible for the production and secretion of Cu-Zn SOD and constructed an isogenic H. ducreyi strain with a mutation in the sodC gene (35000HP-sodC-cat). Compared to the parent, the mutant does not survive in the presence of exogenous superoxide (L. R. San Mateo, M. Hobbs, and T. H. Kawula, Mol. Microbiol. 27:391-404, 1998) and is impaired in the swine model of H. ducreyi infection (L. R. San Mateo, K. L. Toffer, P. E. Orndorff, and T. H. Kawula, Infect. Immun. 67:5345-5351, 1999). To test whether Cu-Zn SOD is important for bacterial survival in vivo, six human volunteers were experimentally infected with 35000HP and 35000HP-sodC-cat and observed for papule and pustule formation. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule formation rates were 75% (95% confidence intervals [CI], 43 to 95%) at 12 parent-inoculated sites and 67% (95% CI, 41 to 88%) at 18 mutant-inoculated sites (P = 0.47). There was no significant difference in levels of H. ducreyi recovery from mutant- and parent-inoculated biopsy sites. These results suggest that expression of Cu-Zn SOD does not play a major role in the survival of this pathogen in the initial stages of experimental infection of humans.

scholarly journals Superoxide Dismutase 1 Loss Disturbs Intracellular Redox Signaling, Resulting in Global Age-Related Pathological Changes

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kenji Watanabe ◽  
Shuichi Shibuya ◽  
Yusuke Ozawa ◽  
Hidetoshi Nojiri ◽  
Naotaka Izuo ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Damage ◽  
Molecular Mechanisms ◽  
The Body ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Age Related ◽  
Tissue Changes ◽  
Copper Zinc

Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD) serves as a major antioxidant and neutralizes superoxide radicals throughout the body.In vivostudies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/−) mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation inSod1−/−mice. This review will focus on various age-related pathologies caused by the loss ofSod1and will discuss the molecular mechanisms underlying the pathogenesis inSod1−/−mice.

scholarly journals Superoxide Dismutase 1 Nanozyme for Treatment of Eye Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Olga A. Kost ◽  
Olga V. Beznos ◽  
Nina G. Davydova ◽  
Devika S. Manickam ◽  
Irina I. Nikolskaya ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Clinical Findings ◽  
Therapeutic Modality ◽  
Superoxide Dismutase 1 ◽  
Histological Data ◽  
Copolymer Poly ◽  
Electrostatic Coupling

Use of antioxidants to mitigate oxidative stress during ocular inflammatory diseases has shown therapeutic potential. This work examines a nanoscale therapeutic modality for the eye on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1), termed “nanozyme.” The nanozyme is produced by electrostatic coupling of the SOD1 with a cationic block copolymer, poly(L-lysine)-poly(ethyleneglycol), followed by covalent cross-linking of the complexes with 3,3′-dithiobis(sulfosuccinimidylpropionate) sodium salt. The ability of SOD1 nanozyme as well as the native SOD1 to reduce inflammatory processes in the eye was examinedin vivoin rabbits with immunogenic uveitis. Results suggested that topical instillations of both enzyme forms demonstrated anti-inflammatory activity; however, the nanozyme was much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as the intensities of corneal and iris edema, hyperemia of conjunctiva, lens opacity, fibrin clots, and the protein content in aqueous humor. Clinical findings were confirmed by histological data. Thus, SOD1-containing nanozyme is potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.

scholarly journals Copper-zinc superoxide dismutase deficiency impairs sperm motility and in vivo fertility

Reproduction ◽  
2013 ◽  
Vol 146 (4) ◽  
pp. 297-304 ◽  
Author(s):  
Michael Garratt ◽  
Roslyn Bathgate ◽  
Simon P de Graaf ◽  
Robert C Brooks
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Sperm Motility ◽  
Physiological Role ◽  
Enzymatic Antioxidants ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc ◽  
And Function

Oxidative stress, overproduction of reactive oxygen species (ROS) in relation to defence mechanisms, is considered to be a major cause of male infertility. For protection against the deleterious effects of ROS, animals have a variety of enzymatic antioxidants that reduce these molecules to less reactive forms. The physiological role of these antioxidantsin vivohas been explored extensively through genetic inhibition of gene expression; surprisingly, many of these animals remain fertile in spite of increased oxidative stress. Copper-zinc superoxide dismutase-deficient (Sod1−/−) male mice are one such example for whichin vivofertility has been repeatedly reported as normal, although examination of fertility has consisted of simply pairing animals of the same strain and checking for litters. This is a fairly low criterion by which to assess fertility. Herein, we show thatSod1-deficient males have zero fertilisation success in sperm competition trials that pit them against wild-type males of an otherwise identical genetic background and are almost completely infertile when mated singly with females of a different genotype. We also show that various aspects of sperm motility and function are impaired inSod1-deficient mice. Testing the breeding capabilities of mice under more ecologically relevant conditions and with females of different genotypes may help reveal additional physiological causes of infertility.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Superoxide, Xanthine Oxidase and Platelet Reactions: Further Studies on Mechanisms by which Oxidants Influence Platelets

1981 ◽  
Vol 45 (03) ◽  
pp. 290-293 ◽  
Author(s):  
Peter H Levine ◽  
Danielle G Sladdin ◽  
Norman I Krinsky
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome C ◽  
Xanthine Oxidase ◽  
Direct Effect ◽  
Platelet Function ◽  
Experimental Conditions ◽  
Release Reaction

SummaryIn the course of studying the effects on platelets of the oxidant species superoxide (O- 2), Of was generated by the interaction of xanthine oxidase plus xanthine. Surprisingly, gel-filtered platelets, when exposed to xanthine oxidase in the absence of xanthine substrate, were found to generate superoxide (O- 2), as determined by the reduction of added cytochrome c and by the inhibition of this reduction in the presence of superoxide dismutase.In addition to generating Of, the xanthine oxidase-treated platelets display both aggregation and evidence of the release reaction. This xanthine oxidase induced aggreagtion is not inhibited by the addition of either superoxide dismutase or cytochrome c, suggesting that it is due to either a further metabolite of O- 2, or that O- 2 itself exerts no important direct effect on platelet function under these experimental conditions. The ability of Of to modulate platelet reactions in vivo or in vitro remains in doubt, and xanthine oxidase is an unsuitable source of O- 2 in platelet studies because of its own effects on platelets.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Effect of Copper-Zinc Superoxide Dismutase on Endothelium-Dependent Vasodilation in Patients With Essential Hypertension

Hypertension ◽  
1995 ◽  
Vol 26 (6) ◽  
pp. 863-868 ◽  
Author(s):  
Carlos E. García ◽  
Crescence M. Kilcoyne ◽  
Carmine Cardillo ◽  
Richard O. Cannon ◽  
Arshed A. Quyyumi ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Essential Hypertension ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc ◽  
Effect Of Copper

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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