scholarly journals Pro-Aging Effects of Xanthine Oxidoreductase Products

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 839
Author(s):  
Maria Giulia Battelli ◽  
Massimo Bortolotti ◽  
Andrea Bolognesi ◽  
Letizia Polito

The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 227 ◽  
Author(s):  
Miguel Mateu-Sanz ◽  
Juan Tornín ◽  
Bénédicte Brulin ◽  
Anna Khlyustova ◽  
Maria-Pau Ginebra ◽  
...  

Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer’s saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.


2008 ◽  
Vol 410 (2) ◽  
pp. 359-368 ◽  
Author(s):  
Lucía Piacenza ◽  
Gonzalo Peluffo ◽  
María Noel Alvarez ◽  
John M. Kelly ◽  
Shane R. Wilkinson ◽  
...  

There is increasing evidence that Trypanosoma cruzi antioxidant enzymes play a key immune evasion role by protecting the parasite against macrophage-derived reactive oxygen and nitrogen species. Using T. cruzi transformed to overexpress the peroxiredoxins TcCPX (T. cruzi cytosolic tryparedoxin peroxidase) and TcMPX (T. cruzi mitochondrial tryparedoxin peroxidase), we found that both cell lines readily detoxify cytotoxic and diffusible reactive oxygen and nitrogen species generated in vitro or released by activated macrophages. Parasites transformed to overexpress TcAPX (T. cruzi ascorbate-dependent haemoperoxidase) were also more resistant to H2O2 challenge, but unlike TcMPX and TcCPX overexpressing lines, the TcAPX overexpressing parasites were not resistant to peroxynitrite. Whereas isolated tryparedoxin peroxidases react rapidly (k=7.2×105 M−1·s−1) and reduce peroxynitrite to nitrite, our results demonstrate that both TcMPX and TcCPX peroxiredoxins also efficiently decompose exogenous- and endogenously-generated peroxynitrite in intact cells. The degree of protection provided by TcCPX against peroxynitrite challenge results in higher parasite proliferation rates, and is demonstrated by inhibition of intracellular redox-sensitive fluorescence probe oxidation, protein 3-nitrotyrosine and protein–DMPO (5,5-dimethylpyrroline-N-oxide) adduct formation. Additionally, peroxynitrite-mediated over-oxidation of the peroxidatic cysteine residue of peroxiredoxins was greatly decreased in TcCPX overexpressing cells. The protective effects generated by TcCPX and TcMPX after oxidant challenge were lost by mutation of the peroxidatic cysteine residue in both enzymes. We also observed that there is less peroxynitrite-dependent 3-nitrotyrosine formation in infective metacyclic trypomastigotes than in non-infective epimastigotes. Together with recent reports of up-regulation of antioxidant enzymes during metacyclogenesis, our results identify components of the antioxidant enzyme network of T. cruzi as virulence factors of emerging importance.


Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 561 ◽  
Author(s):  
Jose Javier Garcia-Medina ◽  
Elena Rubio-Velazquez ◽  
Elisa Foulquie-Moreno ◽  
Ricardo P Casaroli-Marano ◽  
Maria Dolores Pinazo-Duran ◽  
...  

Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, animal studies and clinical trials dealing with the effect of the antioxidants on DR.


2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Branislav Tomasevic ◽  
Srdjan Glisovic ◽  
Ruzica Jankovic-Tomasevic

The structure and the features of a low-cost ultrasonic phacoemulsification prototype device are described in this paper. The phacoemulsifier was designed to comply with the techniques of modern cataract surgery. The functionality and reliability of the device were confirmed through in vitro experiments and animal studies. The device was designed to minimize surgical trauma: Reduced heat dissipation was achieved by specific power modulation, while the original design of aspiration control assured a reduced surge effect. In order to assess the suitability of the device, phacoemulsification was performed on rabbit eyes with nuclei of medium hardness. Their recovery was closely observed and only mild inflammation caused by surgical trauma was noticed. The device performed well in terms of reliability, ergonomics, and controllability throughout the experiments.


2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Michelle K. Paczosa ◽  
Rebecca J. Silver ◽  
Anne L. McCabe ◽  
Albert K. Tai ◽  
Colin H. McLeish ◽  
...  

ABSTRACT Klebsiella pneumoniae is a Gram-negative bacterial pathogen that causes a range of infections, including pneumonias, urinary tract infections, and septicemia, in otherwise healthy and immunocompromised patients. K. pneumoniae has become an increasing concern due to the rise and spread of antibiotic-resistant and hypervirulent strains. However, its virulence determinants remain understudied. To identify novel K. pneumoniae virulence factors needed to cause pneumonia, a high-throughput screen was performed with an arrayed library of over 13,000 K. pneumoniae transposon insertion mutants in the lungs of wild-type (WT) and neutropenic mice using transposon sequencing (Tn-seq). Insertions in 166 genes resulted in K. pneumoniae mutants that were significantly less fit in the lungs of WT mice than in those of neutropenic mice. Of these, mutants with insertions in 51 genes still had significant defects in neutropenic mice, while mutants with insertions in 52 genes recovered significantly. In vitro screens using a minilibrary of K. pneumoniae transposon mutants identified putative functions for a subset of these genes, including in capsule content and resistance to reactive oxygen and nitrogen species. Lung infections in mice confirmed roles in K. pneumoniae virulence for the ΔdedA, ΔdsbC, ΔgntR, Δwzm-wzt, ΔyaaA, and ΔycgE mutants, all of which were defective in either capsule content or growth in reactive oxygen or nitrogen species. The fitness of the ΔdedA, ΔdsbC, ΔgntR, ΔyaaA, and ΔycgE mutants was higher in neutropenic mouse lungs, indicating that these genes encode proteins that protect K. pneumoniae against neutrophil-related effector functions.


2011 ◽  
Vol 127 (2) ◽  
pp. 419-426 ◽  
Author(s):  
Renan Campos Chisté ◽  
Adriana Zerlotti Mercadante ◽  
Ana Gomes ◽  
Eduarda Fernandes ◽  
José Luís Fontes da Costa Lima ◽  
...  

2017 ◽  
Vol 4 (8) ◽  
pp. 1742-1749 ◽  
Author(s):  
A. Dhall ◽  
A. Burns ◽  
J. Dowding ◽  
S. Das ◽  
S. Seal ◽  
...  

Cerium oxide nanoparticles (CeNPs) are potent reactive oxygen and nitrogen species scavengers and demonstrate beneficial antioxidant properties in both cell culture and animal studies.


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