The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile in Vitro and in Vivo

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 48289

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Co-Guest Editor
Department of Nutrition and Dietetics, School of Physical Education, Sport Science and Dietetics, University of Thessaly, Argonafton 1, 42132 Trikala, Greece
Interests: oxidative stress; free radicals; redox biomarkers; redox nutrition; antioxidant supplementation; polyphenols; exercise; redox toxicology; redox biology
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Special Issue Information

Dear Colleagues,

The approach of using redox biomarkers in the evaluation of the antioxidant profile both in vitro and in vivo has come to the surface again lately. Although usually overlooked, recent scientific evidence indicates that redox biomarkers can become a useful tool with great translational potency in the field of redox biology. As they have been defined by Veskoukis et al. 2019 (10.1016/j.cotox.2018.10.001), a redox biomarker might be an antioxidant molecule modified following interaction with reactive species, the products of the detrimental impact of reactive species on biomolecules and the reactive species per se. Furthermore, terms such as “oxidant” and “pro-oxidant” seem today rather vague, as they have not been fully elucidated. On the same basis, the characterization of a compound as “antioxidant” is not sufficient, since this term does not denote exactly the biological role of a given substance. Indeed, it is not clear whether the molecule in question prevents oxidation of biomolecules or repairs the oxidative modifications they have already undergone. Towards this end, redox biomarkers can putatively offer a valuable service in this area since, when functionally clustered, they might give the appropriate information for the actual role of an antioxidant.      

In this Special Issue, we invite the researchers to contribute both review papers and original research articles that will approach the issue of using biomarkers in order to evaluate on the one hand the antioxidant status of nutritional agents and plant extracts in vitro and on the other hand the redox status of a wide range of organisms in vivo.

Potential topics include but are not limited to the following:

  • Biomarkers used for the evaluation of in vivo antioxidant mechanisms;
  • Biomarkers for assessing the antioxidant activity of plant compounds in vitro;
  • Estimation of redox status in exercise context;
  • Antioxidant status in disease using redox biomarkers;
  • Estimation of redox status in aging;
  • Assessment of the antioxidant status of the host after insulted by pathogenic microorganisms;
  • The role of redox biomarkers evaluating antioxidant status of a great variety of organisms in the past, present, and future;
  • Redox biomarkers assessing antioxidant activity: the field of redox biology under a philosophical and historical aspect.

Prof. Dimitrios Kouretas
Guest Editor

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Published Papers (11 papers)

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Editorial

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3 pages, 158 KiB  
Editorial
The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo
by Aristidis S. Veskoukis, Periklis Vardakas and Dimitrios Kouretas
Antioxidants 2021, 10(5), 805; https://doi.org/10.3390/antiox10050805 - 19 May 2021
Viewed by 1698
Abstract
The present Special Issue of Antioxidants, entitled The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo, ten research articles emphasize the significance of adopting reliable redox biomarkers to determine the antioxidant activities of [...] Read more.
The present Special Issue of Antioxidants, entitled The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo, ten research articles emphasize the significance of adopting reliable redox biomarkers to determine the antioxidant activities of bioactive compounds in vitro and to assess blood and tissue redox status in vivo [...] Full article

Research

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16 pages, 845 KiB  
Article
Biological Effects of Scattered Versus Scanned Proton Beams on Normal Tissues in Total Body Irradiated Mice: Survival, Genotoxicity, Oxidative Stress and Inflammation
by Samia Chaouni, Alexandre Leduc, Frédéric Pouzoulet, Ludovic De Marzi, Frédérique Megnin-Chanet, Dinu Stefan, Jean-Louis Habrand, François Sichel and Carine Laurent
Antioxidants 2020, 9(12), 1170; https://doi.org/10.3390/antiox9121170 - 24 Nov 2020
Cited by 5 | Viewed by 2327
Abstract
Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both [...] Read more.
Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects. Full article
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15 pages, 2059 KiB  
Article
Influence of Long-Term Fasting on Blood Redox Status in Humans
by Françoise Wilhelmi de Toledo, Franziska Grundler, Nikolaos Goutzourelas, Fotios Tekos, Eleni Vassi, Robin Mesnage and Demetrios Kouretas
Antioxidants 2020, 9(6), 496; https://doi.org/10.3390/antiox9060496 - 06 Jun 2020
Cited by 28 | Viewed by 9365
Abstract
Fasting is increasingly practiced to improve health and general well-being, as well as for its cytoprotective effects. Changes in blood redox status, linked to the development of a variety of metabolic diseases, have been recently documented during calorie restriction and intermittent fasting, but [...] Read more.
Fasting is increasingly practiced to improve health and general well-being, as well as for its cytoprotective effects. Changes in blood redox status, linked to the development of a variety of metabolic diseases, have been recently documented during calorie restriction and intermittent fasting, but not with long-term fasting (LF). We investigated some parameters of the blood redox profile in 109 subjects before and after a 10-day fasting period. Fasting resulted in a significant reduction in body weight, improved well-being and had a beneficial modulating effect on blood lipids and glucose regulation. We observed that fasting decreased lipid peroxidation (TBARS) and increased total antioxidant capacity (TAC) in plasma, concomitant with a uric acid elevation, known to be associated with fasting and did not cause gout attacks. Reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase in erythrocytes did not show significant changes. In addition, reduction in body weight, waist circumference, and glucose levels were associated to a reduced lipid peroxidation. Similar results were obtained by grouping subjects on the basis of the changes in their GSH levels, showing that a period of 10 days fasting improves blood redox status regardless of GSH status in the blood. Full article
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16 pages, 1531 KiB  
Article
Total Oxidant and Antioxidant Capacity of Gingival Crevicular Fluid and Saliva in Patients with Periodontitis: Review and Clinical Study
by Joanna Toczewska, Mateusz Maciejczyk, Tomasz Konopka and Anna Zalewska
Antioxidants 2020, 9(5), 450; https://doi.org/10.3390/antiox9050450 - 23 May 2020
Cited by 49 | Viewed by 4018
Abstract
Periodontitis is inextricably linked to oxidative-reductive (redox) imbalance. However, little is still known about the resultant ability to scavenge oxygen free radicals in saliva and gingival crevicular fluid in patients with periodontitis. The multitude of enzymatic and non-enzymatic antioxidants and their synergistic effects [...] Read more.
Periodontitis is inextricably linked to oxidative-reductive (redox) imbalance. However, little is still known about the resultant ability to scavenge oxygen free radicals in saliva and gingival crevicular fluid in patients with periodontitis. The multitude of enzymatic and non-enzymatic antioxidants and their synergistic effects cause an interest in the evaluation of the total antioxidative capacity. Thus, our study aimed to evaluate the total oxidative and antioxidative activity of gingival crevicular fluid and saliva in the periodontitis, as well as to relate these biomarkers to clinical indices of periodontopathy. Additionally, by calculating the oxidative stress index (OSI), the intensity of redox disturbances was also evaluated. Fifty-eight periodontitis patients were included in the study and divided into two subgroups depending on the severity of the disease. In the non-stimulated/stimulated saliva as well as a gingival crevicular fluid of the study group, we found significantly higher OSI and total oxidant status (TOS) as well as lower total antioxidant capacity (TAC). However, the ability to reduce iron ions (FRAP) was significantly lower only in stimulated and non-stimulated saliva of patients with periodontitis. The examined parameters correlated with the periodontium’s clinical condition, which indicates the exacerbation of the inflammatory process. However, TAC, TOS, OSI, and FRAP did not differentiate individual stages of periodontitis. Full article
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18 pages, 1297 KiB  
Article
Effects of Melatonin Administration to Pregnant Ewes under Heat-Stress Conditions, in Redox Status and Reproductive Outcome
by Efterpi Bouroutzika, Dimitrios Kouretas, Serafeim Papadopoulos, Aristidis S. Veskoukis, Ekaterini Theodosiadou, Sotiria Makri, Charilaos Paliouras, Marios-Lazaros Michailidis, Mariangela Caroprese and Irene Valasi
Antioxidants 2020, 9(3), 266; https://doi.org/10.3390/antiox9030266 - 23 Mar 2020
Cited by 21 | Viewed by 3635
Abstract
Heat stress is a known promoter of reactive oxygen species generation, which may compromise pregnancy and foetal development. Melatonin is a pleiotropic molecule that regulates various processes including pregnancy. Thus, it could be used to ameliorate the redox status of pregnant heat-stressed ewes [...] Read more.
Heat stress is a known promoter of reactive oxygen species generation, which may compromise pregnancy and foetal development. Melatonin is a pleiotropic molecule that regulates various processes including pregnancy. Thus, it could be used to ameliorate the redox status of pregnant heat-stressed ewes and the outcome of their pregnancy. Sixty-eight ewes participated in the study, which were allocated into two equal groups, i.e., Melatonin (M) and Control (C) group. All ewes were exposed to heat stress from D0 to D120. In both groups, after oestrus synchronization of ewes, rams were introduced to them for mating (D16). In M group, starting with sponges’ insertion (D0), melatonin implants were administered four-fold every 40 days. Pregnancy diagnosis was performed by means of ultrasonography. Daily evaluation of temperature humidity index (THI), rectal temperature, and breathing rate were performed throughout the study. Blood samples were collected repeatedly from D0 until weaning for assaying redox biomarkers. Milk yield was measured thrice during puerperium. The results showed that melatonin administration throughout pregnancy improved the redox status of heat-stressed ewes and increased the mean number and bodyweight of lambs born per ewe, as well as the milk production. Therefore, melatonin may be used as antioxidant regimen in heat-stressed ewes for improving their reproductive traits. Full article
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14 pages, 1403 KiB  
Article
Nitrosative Stress Biomarkers in the Non-Stimulated and Stimulated Saliva, as well as Gingival Crevicular Fluid of Patients with Periodontitis: Review and Clinical Study
by Joanna Toczewska, Tomasz Konopka, Anna Zalewska and Mateusz Maciejczyk
Antioxidants 2020, 9(3), 259; https://doi.org/10.3390/antiox9030259 - 21 Mar 2020
Cited by 22 | Viewed by 3018
Abstract
Diagnosis of periodontopathy is complex and includes defining the cause, type, stage, and grade of periodontitis. Therefore, alternative diagnostic methods are sought to indicate the progression of inflammation or to determine the effectiveness of therapy. Gingival crevicular fluid (GCF) biomarkers can be particularly [...] Read more.
Diagnosis of periodontopathy is complex and includes defining the cause, type, stage, and grade of periodontitis. Therefore, alternative diagnostic methods are sought to indicate the progression of inflammation or to determine the effectiveness of therapy. Gingival crevicular fluid (GCF) biomarkers can be particularly useful because they most likely reflect the disease process of the periodontal tissues. However, the difficulty of collecting GCF for testing is the reason for the limited use in diagnostics. Because periodontitis is the primary source of nitrogen free radicals in the oral cavity, the aim of the study was to evaluate the biomarkers of nitrosative stress (nitric oxide, peroxynitrite, and S-nitrosothiols) in GCF, non-stimulated and stimulated saliva of 90 patients with periodontitis. The study group was divided into two subgroups, depending on the stage of the disease severity. We showed a significantly higher concentration of all assessed biomarkers in the non-stimulated and stimulated saliva of patients with periodontitis. However, significant changes in GCF has been shown only for peroxynitrite. The studied biomarkers did not correlate with clinical periodontal status, which probably results from their short-duration activity and the impact on a few factors in the oral cavity. Saliva and gingival fluid are not very useful in the differential diagnosis of periodontitis. Full article
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25 pages, 6227 KiB  
Article
Prediction of Antioxidant Activity of Cherry Fruits from UAS Multispectral Imagery Using Machine Learning
by Christos Karydas, Miltiadis Iatrou, Dimitrios Kouretas, Anastasia Patouna, George Iatrou, Nikolaos Lazos, Sandra Gewehr, Xanthi Tseni, Fotis Tekos, Zois Zartaloudis, Evangelos Mainos and Spiros Mourelatos
Antioxidants 2020, 9(2), 156; https://doi.org/10.3390/antiox9020156 - 14 Feb 2020
Cited by 18 | Viewed by 6059
Abstract
In this research, a model for the estimation of antioxidant content in cherry fruits from multispectral imagery acquired from drones was developed, based on machine learning methods. For two consecutive cultivation years, the trees were sampled on different dates and then analysed for [...] Read more.
In this research, a model for the estimation of antioxidant content in cherry fruits from multispectral imagery acquired from drones was developed, based on machine learning methods. For two consecutive cultivation years, the trees were sampled on different dates and then analysed for their fruits’ radical scavenging activity (DPPH) and Folin–Ciocalteu (FCR) reducing capacity. Multispectral images from unmanned aerial vehicles were acquired on the same dates with fruit sampling. Soil samples were collected throughout the study fields at the end of the season. Topographic, hydrographic and weather data also were included in modelling. First-year data were used for model-fitting, whereas second-year data for testing. Spatial autocorrelation tests indicated unbiased sampling and, moreover, allowed restriction of modelling input parameters to a smaller group. The optimum model employs 24 input variables resulting in a 6.74 root mean square error. Provided that soil profiles and other ancillary data are known in advance of the cultivation season, capturing drone images in critical growth phases, together with contemporary weather data, can support site- and time-specific harvesting. It could also support site-specific treatments (precision farming) for improving fruit quality in the long-term, with analogous marketing perspectives. Full article
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18 pages, 1069 KiB  
Article
Compared Phenolic Compound Contents of 22 Commercial Fruit and Vegetable Juices: Relationship to Ex-Vivo Vascular Reactivity and Potential In Vivo Projection
by Alexis Matute, Jessica Tabart, Jean-Paul Cheramy-Bien, Bernard Pirotte, Claire Kevers, Cyril Auger, Valérie Schini-Kerth, Jacques Dommes, Jean-Olivier Defraigne and Joël Pincemail
Antioxidants 2020, 9(2), 92; https://doi.org/10.3390/antiox9020092 - 22 Jan 2020
Cited by 12 | Viewed by 3365
Abstract
The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were used to explore whether the total polyphenol content and/or individual phenolic [...] Read more.
The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were used to explore whether the total polyphenol content and/or individual phenolic compound contents of 22 commercial vegetable (n = 3) and fruit juices [(citrus (n = 5), berries (n = 10), apple (n = 2), pineapple (n = 2)] might be associated with vascular tone. Red juices (particularly blackcurrant) and lemon juice caused the most marked vasorelaxation, its amplitude being endothelium dependent or not according to the volume ratio of juice to initial OB solution Vjuice/VOBS). At volume ratios 5% and 10%, both the juice and OB total polyphenol for all juices and total anthocyanin contents for berry juices significantly correlated with aorta vasorelaxation intensity. This was not the case for total or individual flavonols (except kaempferol) or for total or individual flavanols (except epigallocatechin gallate). If one relates our measured concentrations of individual phenolic compounds in OB to what is known about their physiological concentrations, and given our evidenced correlations between compound concentrations and vasorelaxation intensity, kaempferol, epigallocatechin gallate and peonidin-3-O-glucoside seem to emerge as the interesting phenolic compounds likely to be responsible for the potent vasorelaxation observed with fruit juices, and more particularly blackcurrant ones. Clinical investigation is required, however, to confirm our observations. Full article
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21 pages, 7671 KiB  
Article
Hepatoprotective Effect of the Ethanol Extract of Illicium henryi against Acute Liver Injury in Mice Induced by Lipopolysaccharide
by Md Sodrul Islam, Hui Yu, Lingyan Miao, Zhaoying Liu, Yanfei He and Hongxiang Sun
Antioxidants 2019, 8(10), 446; https://doi.org/10.3390/antiox8100446 - 01 Oct 2019
Cited by 18 | Viewed by 5133
Abstract
The root bark of Illicium henryi has been used in traditional Chinese medicine to treat lumbar muscle strain and rheumatic pain. Its ethanol extract (EEIH) has been previously reported to attenuate lipopolysaccharide (LPS)-induced acute kidney injury in mice. The present study aimed to [...] Read more.
The root bark of Illicium henryi has been used in traditional Chinese medicine to treat lumbar muscle strain and rheumatic pain. Its ethanol extract (EEIH) has been previously reported to attenuate lipopolysaccharide (LPS)-induced acute kidney injury in mice. The present study aimed to evaluate the in vitro antioxidant activities and in vivo protective effects of EEIH against LPS-induced acute liver injury (ALI) in mice as well as explore its molecular mechanisms. The mice were injected intraperitoneally (i.p.) with EEIH at the doses of 1.25, 2.5, and 5.0 mg/kg every day for 5 days. One hour after the last administration, the mice were administered i.p. with LPS (8 mg/kg). After fasting for 12 h, blood and liver tissues were collected to histopathological observation, biochemical assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analyses. EEIH possessed 2,2-diphenyl-1-picrylhydrazil (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiozoline-6-sulfonic acid) disodium salt (ABTS) radical scavenging activities and ferric-reducing antioxidant capacity in vitro. The histopathological examination, serum biochemical analysis, and liver myeloperoxidase (MPO) activity showed that EEIH pretreatment alleviated LPS-induced liver injury in mice. EEIH significantly dose-dependently decreased the mRNA and protein expression levels of inflammatory factors TNF-α, IL-1β, IL-6, and COX-2 in liver tissue of LPS-induced ALI mice via downregulating the mRNA and protein expressions of toll-like receptor 4 (TLR4) and inhibiting the phosphorylation of nuclear factor-κB (NF-κB) p65. Furthermore, EEIH markedly ameliorated liver oxidative and nitrosative stress burden in LPS-treated mice through reducing the content of thiobarbituric acid reactive substances (TBARS), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) levels, restoring the decreased superoxide dismutase (SOD) and reduced glutathione (GSH) levels, and up-regulating nuclear factor erythroid 2 related factor 2 (Nrf2). These results demonstrate that EEIH has protective effects against ALI in mice via alleviating inflammatory response, oxidative and nitrosative stress burden through activating the Nrf2 and suppressing the TLR4/NF-κB signaling pathways. The hepatoprotective activity of EEIH might be attributed to the flavonoid compounds such as catechin (1), 3′,4′,7-trihydroxyflavone (2), and taxifolin (7) that most possibly act synergistically. Full article
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18 pages, 1114 KiB  
Article
Salivary FRAP as A Marker of Chronic Kidney Disease Progression in Children
by Mateusz Maciejczyk, Julita Szulimowska, Katarzyna Taranta-Janusz, Katarzyna Werbel, Anna Wasilewska and Anna Zalewska
Antioxidants 2019, 8(9), 409; https://doi.org/10.3390/antiox8090409 - 18 Sep 2019
Cited by 35 | Viewed by 3764
Abstract
Chronic kidney disease (CKD) is one of the most common modern-age diseases in children. Kidney failure does not reveal any symptoms for a long time; therefore, new biomarkers are sought, preferably those reflecting an early stage of CKD. The aim of our study [...] Read more.
Chronic kidney disease (CKD) is one of the most common modern-age diseases in children. Kidney failure does not reveal any symptoms for a long time; therefore, new biomarkers are sought, preferably those reflecting an early stage of CKD. The aim of our study was to evaluate total antioxidant potential as a biomarker differentiating the degree of CKD advancement. The study included 30 children with CKD and a control group matched by age and gender. Non-stimulated saliva (NWS), stimulated saliva (SWS), plasma and urine were used as study material. Total antioxidant potential was determined spectrophotometrically using the FRAP method (ferric ion reducing antioxidant parameter) by measuring total FRAP and uric acid (UA)-independent FRAP (FRAP-UA). We demonstrated that total FRAP, FRAP-UA and UA were significantly higher in stimulated saliva, as well as urine of CKD patients compared to the controls. These biomarkers increase with the progression of chronic kidney disease and their concentration in SWS reflects their content in urine. Interestingly, salivary FRAP and uric acid clearly differentiate between various stages of CKD as well as between healthy and ill children. Special attention should be paid to total FRAP which—measured in SWS—distinguishes patients with mildly to moderately decreased kidney function from those with severe renal impairment (AUC = 1, sensitivity = 100%, specificity = 100%). Although salivary FRAP may be a potential CKD biomarker in children, further studies are needed in a larger group of patients. Full article
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15 pages, 1286 KiB  
Article
Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease
by Arno R. Bourgonje, Ruben Y. Gabriëls, Martin H. de Borst, Marian L. C. Bulthuis, Klaas Nico Faber, Harry van Goor and Gerard Dijkstra
Antioxidants 2019, 8(9), 351; https://doi.org/10.3390/antiox8090351 - 01 Sep 2019
Cited by 30 | Viewed by 4788
Abstract
Oxidative stress plays a pivotal role in the pathogenesis of inflammatory bowel diseases (IBD). Serum free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Here, we aimed to establish concentrations of serum free thiols in IBD [...] Read more.
Oxidative stress plays a pivotal role in the pathogenesis of inflammatory bowel diseases (IBD). Serum free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Here, we aimed to establish concentrations of serum free thiols in IBD and assessed their discriminating capacity regarding endoscopic disease activity. Albumin-adjusted serum free thiol concentrations were measured in 78 IBD patients (31 Crohn’s disease (CD) and 47 ulcerative colitis (UC) patients) and 50 healthy controls and analyzed for associations with disease parameters and their discriminative value regarding endoscopic disease activity (n = 54) or fecal calprotectin (n = 36) in patients for which those data were available. Mean serum free thiol concentrations were significantly lower in both CD and UC as compared to healthy controls (19.4 ± 3.1 and 17.8 ± 3.4 vs. 21.1 ± 1.9 µmol/g albumin, P < 0.001). Free thiols highly accurately discriminated between mild and moderate-to-severe disease activity, better than fecal calprotectin (FC) levels (AUC = 0.87, P < 0.001 vs. AUC = 0.76, P < 0.05, respectively) and this was maintained after cross-validation (AUC = 0.89, P < 0.001). Serum free thiols are reduced in IBD as compared to healthy controls and strongly correlate with the degree of endoscopic disease activity. Quantifying systemic redox status in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Full article
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