Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2017; 23(44): 7849-7862
Published online Nov 28, 2017. doi: 10.3748/wjg.v23.i44.7849
Intestinal parameters of oxidative imbalance in celiac adults with extraintestinal manifestations
Agnieszka Piatek-Guziewicz, Agata Ptak-Belowska, Magdalena Przybylska-Felus, Pawel Pasko, Pawel Zagrodzki, Tomasz Brzozowski, Tomasz Mach, Malgorzata Zwolinska-Wcislo
Agnieszka Piatek-Guziewicz, Department of Gastroenterology and Hepatology, University Hospital, Cracow 31531, Poland
Agata Ptak-Belowska, Tomasz Brzozowski, Department of Physiology, Jagiellonian University Medical College, Cracow 31531, Poland
Magdalena Przybylska-Felus, Tomasz Mach, Malgorzata Zwolinska-Wcislo, Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, Cracow 31531, Poland
Pawel Pasko, Pawel Zagrodzki, Department of Food Chemistry and Nutrition, Jagiellonian University Medical College, Cracow 30688, Poland
Pawel Zagrodzki, Henryk Niewodniczanski Institute of Nuclear Physics, Cracow 31342, Poland
Author contributions: Piatek-Guziewicz A, Zwolinska-Wcislo M and Ptak-Belowska A designed the research; Piatek-Guziewicz A, Ptak-Belowska A, Przybylska-Felus M, Pasko P and Zagrodzki P performed the research; Ptak-Belowska A analyzed the data; Piatek-Guziewicz A and Zwolinska-Wcislo M wrote the paper; Mach T and Brzozowski T revised and edited the manuscript for final submission.
Supported by Ministry of Science and Higher Education, No. K/ZDS/003811.
Institutional review board statement: The study was reviewed and approved by the Local Ethics Committee at Jagiellonian University Medical College in Cracow, Poland (No. KBET/174/B/2013).
Informed consent statement: All study participants, or their legal guardians, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tomasz Brzozowski, MD, PhD, Professor, Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, Cracow 31-531, Poland. mpbrzozo@cyf-kr.edu.pl
Telephone: +48-12-4211006 Fax:+48-12-4222014
Received: October 11, 2017
Peer-review started: October 11, 2017
First decision: October 18, 2017
Revised: November 3, 2017
Accepted: November 14, 2017
Article in press: November 14, 2017
Published online: November 28, 2017
Processing time: 47 Days and 16.3 Hours
Abstract
AIM

To evaluate selected intestinal parameters of oxidative stress, and antioxidant capacity in adult celiac disease patients with extraintestinal manifestations.

METHODS

The study involved 85 adult patients divided into the following subgroups: (1) patients with newly diagnosed celiac disease (CD) (n = 7); (2) celiac patients not adhering to a gluten-free diet (GFD) (n = 22); (3) patients with CD on the GFD (n = 31); and (4) patients with functional disorders of the gastrointestinal tract, serving as controls (n = 25). Celiac patients presented with non-classic symptoms or extraintestinal manifestations. Standard blood tests including serum antioxidant levels (uric acid, bilirubin, and vitamin D), celiac antibody levels, and histopathological status of duodenal biopsy specimens have been determined. The expression of mRNA for tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 10 (IL-10), superoxide dismutase (SOD), heat-shock protein 70 (HSP-70), hypoxia-inducible factor 1 (HIF-1α), and BAX in the duodenal mucosa of patients was analyzed by reverse transcriptase-polymerase chain reaction.

RESULTS

The mean plasma uric acid level in patients with active CD (newly diagnosed and nonadherent patients) and treated celiac patients was significantly higher than in controls (260.17 ± 53.65 vs 190.8 ± 22.98, P < 0.001, and 261.7 ± 51.79 vs 190.8 ± 22.98, P < 0.001, respectively). The mean bilirubin concentration in active and treated celiac patients was significantly lower than in controls (8.23 ± 5.04 vs 10.48 ± 4.08, P < 0.05 and 8.06 ± 3.31 vs 10.48 ± 4.08, P < 0.05, respectively). The mean plasma vitamin D level was significantly lower in active celiac patients than in treated celiac patients and controls (19.37 ± 9.03 vs 25.15 ± 11.2, P < 0.05 and 19.37 ± 9.03 vs 29.67 ± 5.12, P < 0.001, respectively). The expression of TNF-α, IL-10, and HSP-70 mRNAs was significantly elevated in the celiac groups regardless of the diet when compared with controls. Patients on the GFD presented a significantly lower mRNA expression of TNF-α and IL-10 than in newly diagnosed and nonadherent patients (P < 0.05). The expression of SOD mRNA was significantly elevated in celiac patients compared with controls (P < 0.05), with a significant difference between treated and untreated patients (P < 0.05). The expression of HIF-1α mRNA and BAX mRNA was significantly higher in patients with active CD compared with controls and patients on GFD, while no difference was observed between the latter two groups.

CONCLUSION

Increased intestinal expression of HSP-70 despite GFD indicates that GFD only partially reduced oxidative stress. CD patients exhibited an oxidative imbalance and inflammatory response despite GFD. Uric acid may act as an important antioxidant in CD.

Keywords: Celiac disease; Oxidative stress; Superoxide dismutase; Heat-shock protein 70; Apoptosis; Hypoxia-inducible factor; Uric acid; Vitamin D; Tumor necrosis factor alpha

Core tip: Oxidative stress has been implicated in gliadin toxicity. Additional measures aimed at reducing oxidative imbalance may prove to be effective supplementary therapy. We demonstrated increased duodenal expression of hypoxia-inducible factor 1 (HIF-1α), heat-shock protein 70 (HSP-70), and superoxide dismutase in adult celiac patients with extraintestinal manifestations as a defensive reaction to oxidative stress. Hence, HSP-70 and HIF-1α might be potential novel biomarkers of celiac disease (CD). Increased HSP-70 expression, both in treated and untreated celiac patients, suggests that oxidative stress as well as histopathological alterations in duodenal mucosa persist despite gluten-free diet. Our data confirm the increased serum levels of uric acid in patients with CD compared with controls as a result of oxidative stress.