scholarly journals Effects of Dietary Oat Beta-Glucans on Colon Apoptosis and Autophagy through TLRs and Dectin-1 Signaling Pathways—Crohn’s Disease Model Study

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 321
Author(s):  
Łukasz Kopiasz ◽  
Katarzyna Dziendzikowska ◽  
Małgorzata Gajewska ◽  
Michał Oczkowski ◽  
Kinga Majchrzak-Kuligowska ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Caspase 3 ◽  
Disease Model ◽  
Time Dependent ◽  
Sprague Dawley ◽  
Beta Glucan ◽  
High Molar Mass ◽  
Beta Glucans

Background: Crohn’s disease (CD) is characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission. The aim of this study was to determine the time-dependent effects of dietary oat beta-glucans on colon apoptosis and autophagy in the CD rat model. Methods: A total of 150 Sprague–Dawley rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed with feed without beta-glucans (βG−) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. The expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors, in the colon epithelial cells, was determined using immunohistochemistry and Western blot. Results: The results showed that in rats with colitis, after 3 days of induction of inflammation, the expression of Caspase-3 and LC3B in intestinal epithelial cells did not change, while that of TLR 4 and Dectin-1 decreased. Beta-glucan supplementation caused an increase in the expression of TLR 5 and Dectin-1 with no changes in the expression of Caspase-3 and LC3B. After 7 days, a high expression of Caspase-3 was observed in the colitis-induced animals without any changes in the expression of LC3B and TLRs, and simultaneously, a decrease in Dectin-1 expression was observed. The consumption of feed with βGl or βGh resulted in a decrease in Caspase-3 expression and an increase in TLR 5 expression in the CβGl group, with no change in the expression of LC3B and TLR 4. After 21 days, the expression of Caspase-3 and TLRs was not changed by colitis, while that of LC3B and Dectin-1 was decreased. Feed supplementation with βGh resulted in an increase in the expression of both Caspase-3 and LC3B, while the consumption of feed with βGh and βGl increased Dectin-1 expression. However, regardless of the type of nutritional intervention, the expression of TLRs did not change after 21 days. Conclusions: Dietary intake of βGl and βGh significantly reduced colitis by time-dependent modification of autophagy and apoptosis, with βGI exhibiting a stronger effect on apoptosis and βGh on autophagy. The mechanism of this action may be based on the activation of TLRs and Dectin-1 receptor and depends on the period of exacerbation or remission of CD.

scholarly journals P066 Azathioprine linked with impaired intestinal epithelial regeneration in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S167-S168
Author(s):  
K Borycka-Kiciak ◽  
A Pietrzak ◽  
K Ferenc ◽  
P Pietrzak ◽  
L Janaszek ◽  
...  
Keyword(s):  
Dna Damage ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Caspase 3 ◽  
Surrogate Marker ◽  
Preoperative Treatment ◽  
Intestinal Epithelial ◽  
Epithelial Regeneration ◽  
E Cadherin

Abstract Background In patients operated due to active Crohn’s disease (CD), the negative effect of steroids and biologics on septic complications is known. Until now, azathioprine (AZA) is considered to be safe. The aim of our study was to assess the impact of AZA on intestinal epithelial cells damage in patients with active CD as a surrogate marker of healing. Methods Intestinal specimens taken from macroscopically healthy surgical margins of all consecutive CD patients operated due to active isolated ileocecal disease during the study period (2014–2016) were evaluated. Expression of caspase-3, p-53 and Ki-67 as markers of cell apoptosis, DNA damage and proliferation were immunohistochemically tested and assessed using a confocal microscope and microimage for in-tissue-cytometry analysis. Western-blot analysis was performed for the evaluation of cellular integrity using ZO-1 and E-cadherin as a markers. 30-day clinical outcomes were assessed. The study was approved by the institutional Ethics Committee. Results From 61 operated due to active CD patients, 35 met the inclusion criteria. Patients were divided accordingly to preoperative treatment: treated with no immunomodulators (N-9 patients), on steroids (S-14 patients), on AZA (A-6 patients), and on combination therapy, AZA + steroids (AS-6 patients). There were no substantial differences between groups. We found statistically significant increase of apoptosis in A group compared with N (5.33 ± 1.05 vs. 1.29 ± 0.51, p = 0.011), but also S group (1.58 ± 0.68, p = 0.014) and increase of DNA damage in A, AS and S groups compared with N group (p =0.01; p = 0.032; p = 0.035, respectively) (Figure 1a–c). P53-mediated cell cycle arrest and apoptosis through a caspase-3-dependent pathway in response to DNA damage was the most intensive in A group (Figure 2a). Reduction of cell proliferative activity in group A did not reach statistical significance (p = 0,057). A reduction of ZO-1 in A group and increased level of E-cadherin in S group were found. The effect of the decreased number of tight junctions and disintegration of the mucosa layer was observed in A group (Figure 2b). Clinically, in 30-day postoperative follow-up, six wound healing complications and one anastomotic leak were found, all in patients treated with immunomodulators. Conclusion We found that in epithelial cells of the small and large intestine of patients treated with AZA, apoptotic activity and DNA damage processes are increased when regeneration processes and mucosal integrity are significantly disturbed. These abnormalities of intestinal epithelial regeneration may be a surrogate marker of impaired mucosal healing.

scholarly journals Time-Dependent Indirect Antioxidative Effects of Oat Beta-Glucans on Peripheral Blood Parameters in the Animal Model of Colon Inflammation

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 375 ◽  
Author(s):  
Łukasz Kopiasz ◽  
Katarzyna Dziendzikowska ◽  
Małgorzata Gajewska ◽  
Jacek Wilczak ◽  
Joanna Harasym ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Peripheral Blood ◽  
Molar Mass ◽  
Time Dependent ◽  
Mean Corpuscular Hemoglobin ◽  
Beta Glucan ◽  
High Molar Mass ◽  
Colon Inflammation ◽  
Beta Glucans

Background: Oat beta-glucans are polysaccharides, belonging to soluble fiber fraction, that show a wide spectrum of biological activity. The aim of this study was to evaluate the time-dependent antioxidative effect of chemically pure oat beta-glucan fractions, characterized by different molar mass, which were fed to animals with early stage of 2,4,6-trinitrobenzene sulfonic acid (TNBS) - induced colitis. Methods: The study was conducted on 150 adult male Sprague Dawley rats assigned to two groups—healthy control (H) and colitis (C) with colon inflammation induced by per rectum administration of TNBS. The animals from both groups were divided into 3 nutritional subgroups, receiving for 3, 7 or 21 days AIN-93M feed without beta-glucan (βG−) or with 1% (w/w) low molar mass oat beta-glucan (βGl+) or 1% (w/w) high molar mass oat beta-glucan (βGh+). After 3, 7 and 21 days, the animals were euthanized, peripheral blood was collected from the heart for further analysis. Results: The results of analyses performed on blood samples showed small changes in lymphocytes count and red blood cell parameters such as the number of red blood cell, mean corpuscular hemoglobin concentration and mean corpuscular volume (RBC, MCHC, MCV respectively) as well as normalization of antioxidant potential accompanying moderate inflammatory state of colon mucosa and submucosa. Conclusion: Oat beta-glucans exert an indirect antioxidant effect in animals with TNBS-induced colitis, with greater effectiveness in removing systemic effects of colon inflammation found for low molar mass oat beta-glucan.

scholarly journals Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn’s Disease Model: Time- and Molar Mass-Dependent Effects

2021 ◽  
Vol 22 (9) ◽  
pp. 4485
Author(s):  
Ewa Żyła ◽  
Katarzyna Dziendzikowska ◽  
Dariusz Kamola ◽  
Jacek Wilczak ◽  
Rafał Sapierzyński ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Signaling Pathways ◽  
Inflammatory Markers ◽  
Acute Inflammation ◽  
Molar Mass ◽  
Cytokine Signaling ◽  
Trinitrobenzene Sulfonic Acid ◽  
Beta Glucan ◽  
Beta Glucans

Background: The incidence of Crohn’s disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient’s lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (colitis) in the early stages of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD in an animal model. Methods: Sprague–Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively. Results: Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of colitis. Conclusions: Dietary oat beta-glucans can reduce colitis at the molecular and organ level and accelerate CD remission.

Mycobacterial infection influences bone biomarker levels in patients with Crohn’s disease

2018 ◽  
Vol 96 (7) ◽  
pp. 662-667 ◽  
Author(s):  
Amna Naser ◽  
Ahmad Qasem ◽  
Saleh A. Naser
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mycobacterium Avium ◽  
Disease Model ◽  
Mycobacterial Infection ◽  
Undercarboxylated Osteocalcin ◽  
Healthy Cattle ◽  
The Mean ◽  
Mycobacterium Avium Subsp Paratuberculosis ◽  
Active Inflammation

Patients with Crohn’s disease (CD) have higher risk for osteoporosis following decreased level of osteocalcin. We hypothesize that active inflammation following Mycobacterium avium subsp. paratuberculosis (MAP) infection results in elevation of undercarboxylated osteocalcin (ucOC) and downregulation of active osteocalcin in CD patients and cow-disease model (Johne’s disease). In this study, we measured ucOC, active osteocalcin, and calcium levels in sera from 42 cattle (21 infected with MAP and 21 healthy cattle), 18 CD patients, and 20 controls. The level of ucOC in MAP+ bovine samples was higher than that in MAP− controls (318 ± 57.2 nmol/mL vs. 289 ± 95.8 nmol/mL, P > 0.05). Consequently, mean calcium level in bovine MAP+ was significantly higher than that in bovine-MAP− samples (9.98 ± 0.998 mg/dL vs. 7.65 ± 2.12 mg/dL, P < 0.05). Also, the level of ucOC was higher in CD-MAP+ than in CD-MAP− (561 ± 23.7 nmol/mL vs. 285 ± 19.6 nmol/mL, P < 0.05). Interestingly, the mean osteocalcin level in MAP+ bovine was lower than that in MAP− bovine (797 ± 162 pg/mL vs. 1190 ± 43 pg/mL) and it was lower in CD-MAP+ than in CD-MAP− infection (1.89 ± 0.184 ng/mL vs. 2.19 ± 0.763 ng/mL) (P < 0.05). The correlation between MAP infection and elevation of sera ucOC, reduction of active osteocalcin and increased calcium supports MAP infection role in CD and complications with osteoporosis.

scholarly journals Emu oil offers protection in Crohn’s disease model in rats

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Bhaskar Vemu ◽  
S. Selvasubramanian ◽  
V. Pandiyan
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Model ◽  
Emu Oil
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