scholarly journals Treatment of Acute Kidney Injury Using a Dual Enzyme Embedded Zeolitic Imidazolate Frameworks Cascade That Catalyzes In Vivo Reactive Oxygen Species Scavenging

Author(s):  
Xinyue Hou ◽  
Jianxiang Shi ◽  
Jie Zhang ◽  
Zhigang Wang ◽  
Sen Zhang ◽  
...  

Significant advances have been made in recent years for the utilization of natural enzymes with antioxidant properties to treat acute kidney injury (AKI). However, these enzymes have been of limited clinical utility because of their limited cellular uptake, poor pharmacokinetic properties, and suboptimal stability. We employed a novel biomimetic mineralization approach to encapsulate catalase (CAT) and superoxide dismutase (SOD) in a zeolitic imidazolate framework-8 (ZIF-8). Next, this SOD@CAT@ZIF-8 complex was anchored with MPEG2000-COOH to yield an MPEG2000-SOD@CAT@ZIF-8 (PSCZ) composite. The composite was then used as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI, remarkably improved intracellular enzyme delivery. This dual-enzyme-embedded metal-organic framework could effectively scavenge reactive oxygen species. In conclusion, the ZIF-8-based “armor plating” represents an effective means of shielding enzymes with improved therapeutic utility to guide the precision medicine-based treatment of AKI.

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Peter Mittwede ◽  
Lusha Xiang ◽  
Silu Lu ◽  
John Clemmer ◽  
Robert Hester

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0195758 ◽  
Author(s):  
Hyung Ho Lee ◽  
Sook Young Kim ◽  
Joon Chae Na ◽  
Young Eun Yoon ◽  
Woong Kyu Han

2020 ◽  
Author(s):  
Liang Sun ◽  
Anuj K. Sharma ◽  
Byung-Hee Han ◽  
Liviu M. Mirica

<p>Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the cause and progression of this disorder are not completely understood. While the main hallmark of AD is the deposition of amyloid plaques consisting of the β-amyloid (Aβ) peptide, transition metal ions are also known to play a significant role in disease pathology by expediting the formation of neurotoxic soluble β-amyloid (Aβ) oligomers, reactive oxygen species (ROS), and oxidative stress. Thus, bifunctional metal chelators that can control these deleterious properties are highly desirable. Herein, we show that amentoflavone (AMF) – a natural biflavonoid compound, exhibits good metal-chelating properties, especially for chelating Cu<sup>2+</sup> with very high affinity (pCu<sub>7.4</sub> = 10.44). In addition, AMF binds to Aβ fibrils with a high affinity (<i>K<sub>i</sub></i> = 287 ± 20 nM) – as revealed by a competition thioflavin T (ThT) assay, and specifically labels the amyloid plaques <i>ex vivo</i> in the brain sections of transgenic AD mice – as confirmed via immunostaining with an Ab antibody. The effect of AMF on Aβ<sub>42</sub> aggregation and disaggregation of Aβ<sub>42</sub> fibrils was also investigated, to reveal that AMF can control the formation of neurotoxic soluble Aβ<sub>42</sub> oligomers, both in absence and presence of metal ions, and as confirmed via cell toxicity studies. Furthermore, an ascorbate consumption assay shows that AMF exhibits potent antioxidant properties and can chelate Cu<sup>2+</sup> and significantly diminish the Cu<sup>2+</sup>-ascorbate redox cycling and reactive oxygen species (ROS) formation. Overall, these studies strongly suggest that AMF acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity, can also bind Cu<sup>2+</sup> and mediate its deleterious redox properties, and thus AMF has the potential to be a lead compound for further therapeutic agent development for AD. </p>


2021 ◽  
Author(s):  
Małgorzata Olszowy-Tomczyk

AbstractOxidative stress, associated with an imbalance between the oxidants (reactive oxygen species) and the antioxidants in the body, contributes to the development of many diseases. The body’s fight against reactive oxygen species is supported by antioxidants. Nowadays, there are too many analytical methods, but there is no one universal technique for assessing antioxidant properties. Moreover, the applied different ways of expressing the results lead to their incompatibility and unreasonable interpretation. The paper is a literature review concerning the most frequent ways of antioxidant activities expression and for an easy and universal method of the obtained results discussion. This paper is an attempt to point out their disadvantages and advantages. The manuscript can support the searching interpretation of the obtained results which will be a good tool for the development of a number of fields, especially medicine what can help in the future detection and treatment of many serious diseases. Graphic abstract


2018 ◽  
Vol 19 (12) ◽  
pp. 4078 ◽  
Author(s):  
Dahn Clemens ◽  
Michael Duryee ◽  
Cleofes Sarmiento ◽  
Andrew Chiou ◽  
Jacob McGowan ◽  
...  

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.


2017 ◽  
Vol 165 (4) ◽  
pp. 213-222 ◽  
Author(s):  
Kelvin Kiran Anthony ◽  
Dominic Soloman George ◽  
Hasvinder Kaur Baldev Singh ◽  
Shi Ming Fung ◽  
Vicknesha Santhirasegaram ◽  
...  

Author(s):  
Marta Goschorska ◽  
Izabela Gutowska ◽  
Irena Baranowska-Bosiacka ◽  
Katarzyna Piotrowska ◽  
Emilia Metryka ◽  
...  

It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.


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