Biological Activity of Mammalian Metabolites of Antioxidants

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 11281

Special Issue Editor


E-Mail Website
Guest Editor
Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic
Interests: polyphenols; flavonolignans; Silybum marianum; flavonols; quercetin; rutin; isoquercitrin; metabolites; gut microbiota; biotransformation by enzymes and whole cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Exogenous antioxidants, such as polyphenols, often suffer from low bioavailability due to their extensive metabolism in the human body. This leads, among other things, to considerable discrepancies between the results of in vitro antioxidant assays and in vivo biological activity. The metabolites of antioxidants present in blood plasma of humans, after their consumption, often have different biological properties compared with the parent compounds. Inactivation or modulation of their activities, as well as toxication, can occur. Metabolites of bioactive antioxidants are usually not commercially available and, therefore, their preparation is crucial to detailed studies of their properties. They are also required as authentic standards for metabolic studies both ex vivo and in vivo. Due to the complexity of antioxidant molecules, both chemical and enzymatic methods might be useful in the preparation of their (tentative) metabolites in amounts allowing for the determination of their biophysical and biological properties.

This Special Issue focuses on this aspect of antioxidants, which to date has been neglected. Potential topics for this Special Issue include the preparation of metabolites of antioxidants using both chemical and enzymatic methods, the identification and isolation of metabolites from biological material, advanced analytical methods for the characterization of metabolites of antioxidants, and studies of the biological activity of these metabolites in vitro and in cellulo. Comparisons with parent compounds are highly recommended. In case the metabolites are not available, their probable formation should be at least discussed. Studies determining the metabolic profile of natural or synthetic antioxidants in the human or animal body together with e.g. plasma antioxidant capacity are also welcome.

We welcome original research articles or reviews dealing with the biological activity of mammalian metabolites of natural and synthetic antioxidants. The major requirements are: (i) clear novelty; (ii) reproducibility; and (iii) defined structures. Papers dealing with poorly defined mixtures, extracts, or “principles” will be returned without further review.

Dr. Kateřina Valentová
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolites
  • antioxidants
  • enzymatic synthesis
  • bioavailability
  • biological activity
  • toxicity
  • metabolic studies

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

10 pages, 1330 KiB  
Article
Metabolism of 2,3-Dehydrosilybin A and 2,3-Dehydrosilybin B: A Study with Human Hepatocytes and Recombinant UDP-Glucuronosyltransferases and Sulfotransferases
by Jiří Vrba, Barbora Papoušková, Kateřina Lněničková, Pavel Kosina, Vladimír Křen and Jitka Ulrichová
Antioxidants 2021, 10(6), 954; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10060954 - 14 Jun 2021
Cited by 3 | Viewed by 1999
Abstract
2,3-Dehydrosilybin A and 2,3-dehydrosilybin B are a pair of enantiomers formed by the oxidation of the natural flavonolignans silybin A and silybin B, respectively. However, the antioxidant activity of 2,3-dehydrosilybin molecules is much stronger than that of their precursors. Here, we investigated the [...] Read more.
2,3-Dehydrosilybin A and 2,3-dehydrosilybin B are a pair of enantiomers formed by the oxidation of the natural flavonolignans silybin A and silybin B, respectively. However, the antioxidant activity of 2,3-dehydrosilybin molecules is much stronger than that of their precursors. Here, we investigated the biotransformation of pure 2,3-dehydrosilybin A and 2,3-dehydrosilybin B in isolated human hepatocytes, and we also aimed to identify human UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) with activity toward their respective enantiomers. After incubation with hepatocytes, both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B were converted to hydroxyl derivatives, methylated hydroxyl derivatives, methyl derivatives, sulfates, and glucuronides. The products of direct conjugations predominated over those of oxidative metabolism, and glucuronides were the most abundant metabolites. Furthermore, we found that recombinant human UGTs 1A1, 1A3, 1A7, 1A8, 1A9, and 1A10 were capable of catalyzing the glucuronidation of both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B. UGTs 1A1 and 1A7 showed the highest activity toward 2,3-dehydrosilybin A, and UGT1A9 showed the highest activity toward 2,3-dehydrosilybin B. The sulfation of 2,3-dehydrosilybin A and B was catalyzed by SULTs 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C2, 1C4, and 1E1, of which SULT1A3 exhibited the highest activity toward both enantiomers. We conclude that 2,3-dehydrosilybin A and B are preferentially metabolized by conjugation reactions, and that several human UGT and SULT enzymes may play a role in these conjugations. Full article
(This article belongs to the Special Issue Biological Activity of Mammalian Metabolites of Antioxidants)
Show Figures

Graphical abstract

17 pages, 4040 KiB  
Article
Dehydroflavonolignans from Silymarin Potentiate Transition Metal Toxicity In Vitro but Are Protective for Isolated Erythrocytes Ex Vivo
by Zuzana Lomozová, Václav Tvrdý, Marcel Hrubša, Maria Carmen Catapano, Kateřina Macáková, David Biedermann, Radim Kučera, Vladimír Křen, Přemysl Mladěnka and Kateřina Valentová
Antioxidants 2021, 10(5), 679; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10050679 - 27 Apr 2021
Cited by 1 | Viewed by 2173
Abstract
2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: [...] Read more.
2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: in general, DHS appeared to be a more potent iron and copper chelator, and a copper reducing agent under acidic conditions, while DHSCH was a more potent copper reducing agent under neutral conditions. In the next step, both DHS and DHSCH were tested for metal-based Fenton chemistry in vitro using HPLC with coulometric detection. Neither of these compounds were able to block the iron-based Fenton reaction and, in addition, they mostly intensified hydroxyl radical production. In the copper-based Fenton reaction, the effect of DHSCH was again prooxidant or neutral, while the effect of DHS was profoundly condition-dependent. DHS was even able to attenuate the reaction under some conditions. Interestingly, both compounds were strongly protective against the copper-triggered lysis of red blood cells, with DHSCH being more potent. The results from this study indicated that, notwithstanding the prooxidative effects of both dehydroflavonolignans, their in vivo effect could be protective. Full article
(This article belongs to the Special Issue Biological Activity of Mammalian Metabolites of Antioxidants)
Show Figures

Graphical abstract

Review

Jump to: Research

29 pages, 1408 KiB  
Review
The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis
by Nicoleta Bianca Tudorachi, Eugenia Eftimie Totu, Adrian Fifere, Valeriu Ardeleanu, Veronica Mocanu, Cornelia Mircea, Ibrahim Isildak, Katarina Smilkov and Elena Mihaela Cărăuşu
Antioxidants 2021, 10(6), 985; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10060985 - 21 Jun 2021
Cited by 52 | Viewed by 6029
Abstract
Knee osteoarthritis (KOA) is a chronic multifactorial pathology and a current and essential challenge for public health, with a negative impact on the geriatric patient’s quality of life. The pathophysiology is not fully known; therefore, no specific treatment has been found to date. [...] Read more.
Knee osteoarthritis (KOA) is a chronic multifactorial pathology and a current and essential challenge for public health, with a negative impact on the geriatric patient’s quality of life. The pathophysiology is not fully known; therefore, no specific treatment has been found to date. The increase in the number of newly diagnosed cases of KOA is worrying, and it is essential to reduce the risk factors and detect those with a protective role in this context. The destructive effects of free radicals consist of the acceleration of chondrosenescence and apoptosis. Among other risk factors, the influence of redox imbalance on the homeostasis of the osteoarticular system is highlighted. The evolution of KOA can be correlated with oxidative stress markers or antioxidant status. These factors reveal the importance of maintaining a redox balance for the joints and the whole body’s health, emphasizing the importance of an individualized therapeutic approach based on antioxidant effects. This paper aims to present an updated picture of the implications of reactive oxygen species (ROS) in KOA from pathophysiological and biochemical perspectives, focusing on antioxidant systems that could establish the premises for appropriate treatment to restore the redox balance and improve the condition of patients with KOA. Full article
(This article belongs to the Special Issue Biological Activity of Mammalian Metabolites of Antioxidants)
Show Figures

Figure 1

Back to TopTop