https://doi.org/10.52973/rcfcv-e34351
Received: 14/11/2023 Accepted: 05/01/2024 Published: 11/03/2024
1 of 9
Revista Científica, FCV-LUZ / Vol. XXXIV, rcfcv-e34351
ABSTRACT
This study investigated the histopathological and
immunohistochemical effect on the intestine and liver tissues with
addition of the soybean meal (SBM), wheat Gluten meal (WGM) and
Corn gluten meal (CGM) to rat diet. A total of 24 average twenty–
day–old male rats (Wistar albino) were used in the study. The rats
were randomly divided into 3 groups with 8 animals in each group
(Control, Wheat and Corn groups). The diet provided to all three groups
contained proteins, which were SBM, WGM and CGM in the Control,
Wheat and Corn groups, respectively. In the study, the group fed with
SBM was used as the Control group. Rats were fed a diet containing
22% crude protein and 2,598 kcal·kg
-1
metabolic energy throughout
the experimental period. The feeding trial was continued for a period
of 50 days. Degenerative changes of varying severity in intestinal
epithelial cells and atrophy in villi were observed. Similarly, the
degenerative changes, especially vacuolar or hydropic degeneration
were determined in hepatocytes. It was determined that the CD4 level
compared to the Control group (P<0.01) on intestine tissue. Also, it was
of the Wheat and Corn groups in liver tissue. (P<0.05). As a result, it
was observed that the histopathological and immunohistochemical
parameters of the intestine and liver tissues of the rats fed with diets
containing highly WGM and CGM were limitedly affected.
Key words: Autoimmune; gluten; histopathology; intestine; liver
RESUMEN
Este estudio investigó el efecto histopatológico e inmunohistoquímico
en los tejidos del intestino y el hígado con la adición de harina de soja
(SBM), harina de gluten de trigo (WGM) y harina de gluten de maíz (CGM)
a la dieta de ratas. En el estudio se utilizaron un total de 24 ratas
macho (Wistar albino) de veinte días de edad promedio. Las ratas se
dividieron aleatoriamente en 3 grupos con 8 animales en cada grupo
(grupos Control, Trigo y Maíz). La dieta proporcionada a los tres grupos
contenía proteínas, que eran SBM, WGM y CGM en los grupos Control,
Trigo y Maíz, respectivamente. En el estudio, el grupo alimentado con
SBM se utilizó como grupo Control. Las ratas fueron alimentadas
-1
de energía metabólica durante todo el período experimental. La
prueba de alimentación continuó durante un período de 50 días. Se
observaron cambios degenerativos de diversa gravedad en las células
en los hepatocitos se determinaron los cambios degenerativos,
especialmente la degeneración vacuolar o hidrópica. Se determinó
en los grupos de trigo y maíz en comparación con el grupo de control
(P<0,01) en el tejido intestinal. Además, se determinó que el nivel de
hepático de los grupos Trigo y Maíz. (P<0,05). Como resultado, se
observó que los parámetros histopatológico e inmunohistoquímico
de los tejidos del intestino y del hígado de las ratas alimentadas con
dietas que contenían un alto contenido de WGM y CGM se vieron
afectados de forma limitada.
Palabras clave: Autoinmune; gluten; histopatología; intestino;
hígado
The effect of adding wheat and corn gluten to the diet of rats on the
autoimmune and histopathological parameters in the intestine and liver
El efecto de la adición de gluten de trigo y maíz a la dieta de ratas sobre los
parámetros autoinmunes e histopatológicos en el intestino y el hígado
Recep Gümüş
1
* , Kübra Asena Terim Kapakin
2
, Esra Manavoğlu Kirman
2
, İsmail Bolat
2
, Aybuke İmik
3
, Nazlı Ercan
4
1
Sivas Cumhuriyet University, Faculty of Veterinary Medicine, Department of Animal Nutrition and Nutritional Diseases. Sivas, Türkiye.
2
Ataturk University, Faculty of Veterinary Medicine, Department of Veterinary Pathology. Erzurum, Türkiye.
3
Selçuk University, Faculty of Health Sciences, Department of Nutrition and Dietetics. Konya, Türkiye.
4
Sivas Cumhuriyet University, Faculty of Veterinary Medicine, Department of Biochemistry, Sivas, Türkiye.
*Corresponding author: rgumus@cumhuriyet.edu.tr
Dietary Wheat & Corn Gluten: Autoimmunity & Intestinal/Liver Pathology in Rats / Gümüş et al. ___________________________________
2 of 9
INTRODUCTION
Cereals are one of the main foods for both humans and animals.
Wheat (Triticum aestivum L.) and corn (Zea mays L.), which are the
main cereal products, are among the most important food products
in the World that are grown and consumed Worldwide [1]. Protein in
wheat consists of 10–15% of albumin/globulin and 85–90% of glüten
[2]. Gluten is a complex mixture of hundreds of different proteins,
primarily gliadin and glutenin. Gliadin and glutenin proteins are termed
prolamins, which represent seed proteins that are insoluble in water
but can be extracted in aqueous ethanol and are characterized by
high levels of glutamine (38%) and proline residues (20%) [2, 3]. Corn
is the most produced product among cereals after wheat, and corn
gluten meal obtained from corn is accepted as a high quality protein
source with desired functionality for food application [4]. Corn gluten
contains approximately 62–74% zein as a protein fraction [5].
Wheat gluten is the main factor that causes some diseases and
allergies in living beings with carrying the HLA–DQ2/8 genes [6].
Due to the harmful immune response to the gluten proteins found in
wheat, cases of gluten intolerance have been reported which people
cannot tolerate wheat consumption [7]. The most common disorders
associated with gluten intake are celiac disease, gluten intolerance,
non–celiac gluten sensitivity (NCGS), wheat allergy, and dermatitis
herpetiformis [3]. It has been reported that gluten causes intestine
and liver damage with an increase in the transglutaminase enzyme and
gliadin level due to liver dysfunctions plays a role in the pathogenesis
in celiac patients with an autoimmune disease [8, 9].
This study was aimed to determine the effects of glutens (WGM and
CGM), incorporated as protein sources into rats (Wistar albino) diet,
on histopathological and immunohistochemical effects on intestine
and liver tissues.
MATERIALS AND METHODS
Animals, experimental design and diets
The experimental protocol of the study was approved by the Sivas
Cumhuriyet University Animal Experiments Local Ethics Committee's
decision dated 2021 and numbered 462.
A total of 24 average twenty–day–old male rat (Wistar albino)
were used in the experiment. The rats were randomly divided into 3
groups with 8 animals in each group. The feed diets provided to all
three groups contained of proteins, which were SBM (24.85%), WGM
(24.85%) and CGM (16.80%) in the Control, Wheat and Corn groups,
respectively (TABLE I). The feeding trial was continued for a period
of 50 days. Feed and water were provided ad libitum. The animals
were housed at the comfort temperature (22°C) and were fed on a
diet containing 22% of crude protein and 2,598 kcal·kg
-1
of metabolic
energy throughout the experiment period.
Histopathological examination
At the end of the study eight animals from each group were
sacrificed under anesthesia. The tissue samples were fixed in
10% buffered formalin and routinely processed for histological
cut 4 μm in thickness (Leica RM2125 RTS microtome) and stained
by the Haematoxylin–Eosin for observation under a light microscope
(Olympus Bx51 with a DP72, Tokyo, Japan) [10].
TABLE I
Contents and nutrient composition of diets used in the study (%)
Composition (%)
Groups
Control Wheat Corn
Wheat bran 3.24 1.8 4.55
Oat, 11% CP
1
62.11 68 64.00
Sunower meal, 28% CP
1
6 13 13
Corn gluten meal, 62% CP
1
– – 16.80
Wheat gluten meal, 75% CP
1
– 24.85 –
Soybean meal, 51% CP
1
24.85 – –
Animal fat 2.8 2.2 0.65
Vitamin–mineral premix* 1 1 1
Nutrient composition (calculated)
Metabolisable energy, (kcal·kg
-1
) 2598 2598 2598
Crude protein (%) 22 22 22
*The vitamin–mineral premix provides the following (per kg): vitamin A: 6,000,000 IU,
vitamin D3: 800,000 IU, vitamin E: 8,000 mg, vitamin K3: 2,000 mg, vitamin B1: 1,200
mg, vitamin B2: 3,000 mg, vitamin B6: 2,000 mg, vitamin B12: 8 mg, niacin: 10,000 mg,
folic acid: 400 mg,; d–biotin: 20 mg, choline chloride: 160,000 mg, manganese: 32,000
mg, iron: 16,000 mg, zinc: 24,000 mg, copper: 2,000 mg, iodine: 800 mg, cobalt 200
mg, selenium: 60 mg, Cal–D–Pan: 4,000 mg, antioxidant: 4,000 mg.
1
CP: Crude protein.
Image analysis
Tissue sections were evaluated by high–power light microscopic
examination using an Olympus Bx51 with a DP72 (Tokyo, Japan) camera
system. Each specimens were examined in 10 randomly selected areas
with an 40× objective. The scores were derived semi–quantitatively
using light microscopy on the preparations from each rat and were
reported as follows: Grade 0 = - (negative); Grade 1 = +1 (mild); Grade 2
= +2 (moderate); Grade 3 = +3 (severe); Grade 4 = +4 (most severe) [11].
Immunohistochemical examinations
Four μm sections from all of the tissue samples were cut and
processed for immunohistochemical examination by a standard
avidin–biotin–peroxidase method that the producer described.
Rabit policlonal antibodies that react with rat transglutaminase 2
(TG2) (Catalog No:NB600–547), gliadin (Catalog No: BS–13374–R),
IgA (Catalog No: BS–0648–R10491–R), IgG (Catalog No: BS– 0392–R),
CD4 (Catalog No: BS–0647R, ThermoFisher), and CD8 antibodies
(Catalog No: BS–0648–R) were used for 60 min. A secondary antibody
was used according to the manufacturer’s protocol (expose mouse
PBS, the sections were incubated with 3,3–diaminobenzidine (Dako
Cytomation, Glostrup, Denmark) and counterstained with Mayer’s
hematoxylin (Dako Cytomation) [12, 13].
Statistical analysis
For all analyses, SPSS
®
and P14
expressed as mean ± standard error of the mean (SEM).
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34351
3 of 9
RESULTS AND DISCUSSION
Histopathological ndings in intestine tissue
Degenerative changes of varying severity in intestinal epithelial
mostly accompanied by lymphocytes, plasma and eosinophils and a
small number of neutrophil leukocytes, was observed in the lamina
propria. In addition, hyperplasia in the crypts was among the observed
(FIG. 1).
results are presented in FIG. 2 and TABLE II. The study results
parameters (P>0.05) did not statistically affect with WGM and CGM
supplementation (TABLE II).
Histopathological ndings in liver tissue
While degenerative changes, especially vacuolar or hydropic
degeneration were observed in hepatocytes, necrosis in some
CONTROL WHEAT CORN
H&ETGM2GLIADINIgAIgGCD8
FIGURE 1. H&E: Hematoxylin–eosin staining of the intestine tissue of experimental groups. Apperance of degenerative changes and
necrosis in intestine. Bar: 20 μm. Immunohistochemistry of Transglutaminase 2/TG2, IgG, IgA and CD4 expressions in the intestine
tissue of experimental groups, Bar: 20 μm
FIGURE 2. Histological score of villous atrophy, inflammation and crypt
hyperplasia parameters in intestine tissue of experimental groups. The values
are given as mean ± SEM. (P>0.05) n=5
TABLE II
Values obtained with the hematoxylin–eosin and immunohistochemical
staining of the rats intestine tissue samples
Histopathological Parameters Immunohistochemical Parameters
n
Villous
atrophy
Inammation
Crypt
hyperplasia
TG2 Gliadin IgA IgG CD4
Control Group
1 +2 +2 +2 +1 +1 +1 +1 +1
2 +2 +2 +2 +1 +1 +2 +1 +1
3 +2 +2 +2 0 +1 +1 +1 +1
4 +2 +2 +2 0 0 0 0 0
5 +1 +1 +2 0 0 0 0 0
Wheat Group
1 +3 +4 +3 +2 +1 +2 +2 +3
2 +3 +4 +2 +1 +1 +2 +2 +3
3 +2 +2 +2 +1 +2 +3 +3 +2
4 +2 +3 +2 +1 +1 +1 +1 +2
5 +2 +2 +2 +1 0 +2 +1 +2
Corn Group
1 +2 +3 +2 +1 +1 +2 +2 +2
2 +2 +3 +2 +1 +1 +2 +2 +3
3 +2 +2 +2 +1 +2 +1 +1 +2
4 +2 +2 +1 0 +1 +1 +1 +2
5 +1 +2 +1 0 0 0 0 +1
TG2: Transglutaminase 2, IgA: Immunoglobulin A, IgG: Immunoglobulin G, n=5
Dietary Wheat & Corn Gluten: Autoimmunity & Intestinal/Liver Pathology in Rats / Gümüş et al. ___________________________________
4 of 9
results are presented in FIG. 4 and TABLE III. The study results showed
that WGM and CGM supplementation did not statistically affect
III). However, it was determined that these parameters increased
numerically in Wheat and Corn groups (FIG. 4).
TABLE III
Values obtained with the hematoxylin–eosin and
immunohistochemical staining of the rats liver tissue samples
Histopathological Parameters Immunohistochemical Parameters
n Degeneration Inammation
Biliary
hyperplasia
TG2 IgA IgG CD4 CD8
Control Group
1 +2 +1 +2 +1 +1 +1 +1 +1
2 +2 +1 +2 +2 +1 +1 +1 +1
3 +2 +2 +2 +1 +1 +1 +1 +1
4 +2 +1 +1 +1 +1 +1 +1 +1
5 0 0 0 +1 0 0 +1 +1
6 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0
8 +1 0 0 0 0 0 0 0
Wheat Group
1 +2 +2 +2 +3 +2 +2 +2 +2
2 +3 +1 +2 +3 +2 +2 +2 +3
3 +2 +1 +2 +2 +2 +2 +2 +2
4 +2 +1 +1 +2 +3 +1 +2 +2
5 +2 +2 0 +2 +3 +1 +1 +1
6 +2 0 +1 +1 +2 +1 +1 +1
7 +1 +1 0 +1 +2 +1 +1 +1
8 0 0 +1 0 0 0 0 0
Corn Group
1 +2 +2 +2 +2 +2 +1 +2 +2
2 +2 +1 +2 +2 +2 +1 +2 +2
3 +2 +2 +2 +1 +2 +1 +1 +2
4 +1 +1 +1 +1 +2 +1 +1 +1
5 +1 +1 +1 +1 +1 +1 +1 +1
6 +1 +1 +1 +1 +1 +1 +1 +1
7 +1 0 0 0 0 0 0 0
8 +1 0 0 0 0 0 0 0
TG2: Transglutaminase 2, IgA: Immunoglobulin A, IgG: Immunoglobulin G, n=8
hepatocytes were remarkable findings. Also, lymphocytes and
macrophage had infiltrated in intralobuler and portal areas and
hyperplasia of bile ducts (FIG. 3).
Immunohistochemical ndings in intestine tissue
Immunopositivity was observed in intestinal villi and crypt epithelial
experimental groups (FIG. 1).
The TG2, gliadin, IgG, IgA and CD4 parameters results are presented in
FIG. 5 and TABLE II. In the study, it was determined that CD4 parameter
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34351
5 of 9
CONTROL WHEAT CORN
H&ETGM2GLIADINIgAIgGCD8
FIGURE 3. Hematoxylin–eosin (H&E) staining of the liver tissue of experimental groups. Apperance of degenerative changes and necrosis
in hepatocytes. Bar: 20
μm. Immunohistochemistry of Transglutaminase 2/TG2, IgG, IgA, CD4, and, CD8 expressions in the liver tissue
of experimental groups, Bar: 20
μm
were statistically increased in Wheat and Corn groups compared to
the Control group (P<0.01) (TABLE II). The TG2, gliadin, IgA and IgG
parameters were statistically similar to all groups (P>0.05) (TABLE II).
Immunohistochemical ndings in liver tissue
The TG2, IgG, IgA, CD4 and CD8 parameters results are presented in
FIG. 6 and TABLE III. In the study, it was determined that IgA parameter
was statistically increased (P<0.05), TG2, IgG, CD4 and CD8 parameters
were numerically increased in Wheat and Corn groups compared to
the Control group (P>0.05) (TABLE III).
All groups showed immunopositivity for CD4 antibody, CD8 antibody,
IgA antibody, IgG antibody, and, TG2 antibody in the hepatocytes,
(FIG. 3).
3]. Celiac
FIGURE 4. Histological score of degeneration, inflammation and biliary
hyperplasia parameters in liver tissue of experimental groups. The values are
given as mean ± SEM. (P>0.05) n=8
FIGURE 5. Histological score of TG2, gliadin, IgA, IgG and CD4 parameters in
intestine tissue of experimental groups. TG2: transglutaminase 2. The values
are given as mean ± SEM. a, b: Means in the column with dierent superscripts
dier signicantly, (P<0.01). n=5
FIGURE 6. Histological score of TG2, IgA, IgG, CD4 and CD8 parameters in liver
tissue of experimental groups. TG2: transglutaminase 2. The values are given
as mean ± SEM. a, b, c: Means in the column with dierent superscripts dier
signicantly, (P<0.05). n=8
Dietary Wheat & Corn Gluten: Autoimmunity & Intestinal/Liver Pathology in Rats / Gümüş et al. ___________________________________
6 of 9
to cause gradual villous atrophy and crypt hyperplasia of the small
intestinal mucosa in celiac disease [19, 20]. It has been reported that
this damage changes depending on the dose and duration of gluten
ingested and causes an increase in exposure time and dose increase
[21]. In a study, it was reported that intragastric gliadin administration
to rats from birth to 63 days of age caused various morphological
changes resembling human celiac disease, such as shortening of
jejunal villi, crypt hyperplasia, and increased amount of mitosis in
the crypt epithelium [22]. In another study, it was reported that in
intestinal sections from duodenum and jejunum of rats were observed
neutrophils in the intestinal lumen [23]. In this study, although there
was no statistical difference between the values of villus atrophy,
that these values were numerically higher in the wheat group and
this effect would increase with the prolongation of gluten exposure.
Although liver damage occurs in many celiac patients, these
findings such as inflammatory reaction in the periportal areas,
24
have been reported in some cases [25]. It has been reported that
liver histology typically shows a preserved architecture with mild
and lobular tract, and intraepithelial lymphocytes are also seen in the
interlobular bile ducts as well as the small intestine in some studies
[9
26]. The term celiac hepatitis
disease that resolves after a gluten–free diet [27]. Degeneration,
degeneration parameter increased only in the Wheat group while
disease was thought to only affect the intestines in previous studies.
However, in recent studies, it has been reported that the disease also
affects organs such as the liver, skin, brain and ovarian [13, 15]. For
this reason, it is observed that celiac disease causes multiple organ
disorders [16]. The use of rats that do not carry the HLA–DQ2/8 genes,
terature.
The digestive system is one of the organs most affected by
gluten–containing foods [17]. It is known that these health problems
begin with the digestion and metabolism of gliadin and gluten in
the gastrointestinal tract [18]. Dietary gluten has been reported
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34351
7 of 9
the inflammation and biliary hyperplasia parameters increased
numerically in both the Wheat and Corn groups compared to the
examined.
Gluten–induced celiac disease may present with nonspecific
hepatitis symptoms such as liver dysfunction, weakness and fatigue.
However, patients are usually asymptomatic and may not have signs or
symptoms of celiac disease [26]. Tissue transglutaminase is an enzyme
that deamidates gliadin peptides and increases their immunogenicity
[28]. Studies have shown that hypertransaminases are formed in most
of the people with celiac disease [9, 29, 30] and their transglutaminase
level decreases when a gluten–free diet is applied to them [9]. It has
also been reported that intestinal permeability increases in patients
with high transglutaminase levels in celiac patients although the
liver tests are normal, but the gluten–free diet applied to the patients
normalizes both intestinal permeability and transglutaminase levels [9,
31, 32]. Transaminase antibody secretion was increased, especially in
endothelial cells and periportal hepatocytes, in immunohistochemical
staining of liver tissues in celiac patients was reported in a study [33]. It
was observed that liver tissue TG2 levels increased in the groups given
wheat and corn gluten, and immunopositivity for transglutaminase
cells of glands similarly to this study.
Gliadin is one of the main proteins in gluten. The gliadin antibody
test is used to determine the presence of celiac disease which an
autoimmune disease, and have been reported in higher–than–normal
levels of this antibody over 90% of untreated patients [8, 34]. Gliadin is
presented to gliadin–reactive CD4+ T cells via a T cell receptor which
resulting in the production of cytokines that cause tissue damage
[35]. CD4+ T cells increase the level of T Helper 1 and T Helper 2 as a
and the formation of plasma cells. On the other hand plasma cells
enable the release of gliadin and transglutaminase antibodies [36]. It
has been stated that those with high antigliadin IgG levels represent a
subgroup that may have gluten sensitivity [37]. In a study was reported
that those who consume cereal–containing processed foods have
higher IgG, IgA and IgM antibody responses [38]. TG2 is expressed in
many organs, including the small intestine. Celiac patients on a gluten–
20].
In this study, it was determined that TG2, IgA and IgG expressions
were high in intestinal tissue. Also, in this study was observed that
IgA and IgG levels increased numerically in liver tissue of Wheat and
Corn groups, and immunopositivity for these antibodies occurred in
results are similar to other studies in the literature [20, 38].
39
and mast cells as well as parenchymal cells [40
[41
(80–90%) [42]. It has been suggested that the mucosal changes
43]. It has been
44
45
[46]. Similar to this study, it was observed that CD4 and CD8 levels
in the liver tissue and CD4 levels in the intestines of the groups given
wheat and corn gluten were increased, and immunopositivity against
cells and epithelial cells of the glands. Also, similar to this study, it
was reported that intragastric gliadin administration to rats from
birth to 63 days of age caused an increase in the number of CD8 in the
intestine and this increase may be the result of antigenic stimulation
of lymphocytes in the intraepithelial compartment by gliadin [22].
CONCLUSIONS
In conclusion, it was observed that dietary supplementation
containing wheat Gluten meal and Corn gluten meal increased the
CD4 parameter in the intestine tissue and the IgA parameters in the
effect on other parameters. However, it was concluded that these
results may be related to feeding time and may show parallelism with
Gluten exposure time.
Conicts of interest
The authors have no declaration of competing interests.
BIBLIOGRAPHIC REFERENCES
[1] Biesiekierski JR. What is gluten? J. Gastroenterol. Hepatol.
[Internet]. 2017; 32(51):78–81. doi: https://doi.org/f9st3c
[2] Wieser H. Chemistry of gluten proteins. Food Microbiol.
[Internet]. 2007; 24(2):115–119. doi: https://doi.org/cb957r
Garg M. Pathogenesis of celiac disease and other gluten related
disorders in wheat and strategies for mitigating them. Front.
Nutr. [Internet]. 2020; 7(6):1–26. doi: https://doi.org/mjr2
different frequency modes of a low–power density ultrasound.
Food Chem. [Internet]. 2021; 344:128609. doi: https://doi.org/mjr4
[5] Fevzioglu M, Hamaker BR, Campanella OH. Gliadin and zein show
similar and improved rheological behavior when mixed with
high molecular weight glutenin. J. Cereal Sci. [Internet]. 2012;
55(3):265–271. doi: https://doi.org/fzvggr
Celiac disease and immunogenic wheat gluten peptides and the
association of gliadin peptides with HLA DQ2 and HLA DQ8. Food
Rev. Int. [Internet]. 2022; 38(7):1553–1576. doi: https://doi.org/mjr5
[7] Cabanillas B. Gluten–related disorders: Celiac disease, wheat
allergy, and nonceliac gluten sensitivity. Crit. Rev. Food Sci. Nutr.
[Internet]. 2020; 60(15):2606–2621. doi: https://doi.org/gh2dmv
[8] Freitag TL, Podojil JR, Pearson RM, Fokta FJ, Sahl C, Messing
M, Getts DR. Gliadin nanoparticles induce immune tolerance
to gliadin in mouse models of celiac disease. Gastroenterol.
[Internet]. 2020; 158(6):1667–1681. doi: https://doi.org/gg9g8r
Dietary Wheat & Corn Gluten: Autoimmunity & Intestinal/Liver Pathology in Rats / Gümüş et al. ___________________________________
8 of 9
[9] Novacek G, Miehsler W, Wrba F, Ferenci P, Penner E, Vogelsang
H. Prevalence and clinical importance of hypertransaminasaemia
in coeliac disease. Eur. J. Gastroenterol. Hepatol. [Internet].
1999; 11(3):283–288. doi: https://doi.org/cr8bsn
metabolism in diabetic rats. Biotech. Histochem. [Internet]. 2022;
97(4):269–276. doi: https://doi.org/mjr6
ascorbic and α–lipoic acid on secretion of HSP–70 and apoptosis
in liver and kidneys of broilers exposed to heat stress. Ankara
Univ. Vet. Fak. Derg. [Internet]. 2012; 59(4):279–287. doi: https://
doi.org/mjr8
YS. Respiratory tract infection induced experimentally by
Ornithobacterium rhinotracheale in quails: effects on heat shock
proteins and apoptosis. Revue Méd. Vét. 2013; 164(3):132–140.
Ozkaraca M. The effects of dietary wheat and corn glutens on
the histopathological and immunohistochemical structure of the
ovarian tissue and serum and ovarian tissue LH and FSH levels
2023; 66:e23210726. doi: https://doi.org/mjsc
[14] IBM Corp. Released 2011. IBM SPSS Statistics for Windows,
Version 20.0. Armonk, NY, USA: IBM Corp. 2011.
[15] Fasano A. Clinical presentation of celiac disease in the pediatric
population. Gastroenterol. [Internet]. 2005; 128:68–73. doi:
https://doi.org/bvs6x7
Mustonen J. Celiac disease and HLA DQ in patients with IgA
nephropathy. Am. J. Gastroenterol. [Internet]. 2002; 97(10):2572–
2576. doi: https://doi.org/bshvj7
[17] Sollid LM, Jabri B. Triggers and drivers of autoimmunity: lessons
from coeliac disease. Nat. Rev. Immunol. [Internet]. 2013;
13(4):294–302. https://doi.org/grhbfv
and tissue transglutaminase in dogs with chronic enteritis
and intestinal T–cell lymphoma. Vet. Pathol. [Internet]. 2018;
55(1):98–107. doi: https://doi.org/mjsx
[19] Marsh MN. Gluten, major histocompatibility complex, and the
small intestine. A molecular and immunobiologic approach to
the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterol.
[Internet]. 1992; 102:330–354. doi: https://doi.org/gpmqpv
disorder. Nat. Rev. Immunol. [Internet]. 2002; 2(9):647–655. doi:
https://doi.org/fwrjn8
mucosal changes and antibody responses after low–and moderate–
dose gluten challenge in celiac disease. BMC Gastroenterol.
[Internet]. 2011; 11(129):1–9. doi: https://doi.org/djd6hs
germfree rats with gluten. Scan. J. Gastroenterol. [Internet].
1996; 31(6):551–557. doi: https://doi.org/czb3ng
enteropathy rat model of non–celiac gluten sensitivity. J. Pharm.
Pharmacol. Res. [Internet]. 2021; 5(4):205–217. doi: https://doi.
org/mjs4
[Internet]. 2007;46(5):1650–1658. doi: https://doi.org/d8w88m
[Internet]. 2006; 21(1):332–334. doi: https://doi.org/c2m7nv
review. J. Clin. Transl. Hepatol. [Internet]. 2021; 9(1):116–124.
doi: https://doi.org/mjs5
Minerva Med. 2008; 99(6):595–604. Cited in: PubMed; PMID
19034257.
C, Madsen L, Sollid LM. Tissue transglutaminase selectively
T cells in celiac disease. Nat. Med. [Internet]. 1998; 4:713–717.
doi: https://doi.org/ftkqwt
[29] Bengi G, Duran Y. [Analysis of liver function tests in patients
newly diagnosed with celiac disease]. Turk J. Gastroenterol.
[Internet]. 2019; 18(3):95–100. Turkish. doi: https://doi.org/mjs6
[30] Zanini B, Baschè R, Ferraresi A, Pigozzi MG, Ricci C, Lanzarotto
F, Lanzini, A. Factors that contribute to hypertransaminasemia
in patients with celiac disease or functional gastrointestinal
syndromes. Clin. Gastroenterol. Hepatol. [Internet]. 2014;
12(5):804–810. doi: https://doi.org/f2rgg4
Hogenová H. Serological markers of enterocyte damage and
apoptosis in patients with celiac disease, autoimmune diabetes
mellitus and diabetes mellitus type 2. Physiol. Res. [Internet].
2015;64(4):537–546. doi: https://doi.org/mjs7
[32] Spadoni I, Zagato E, Bertocchi A, Paolinelli R, Hot E, Di Sabatino
A, Rescigno M. A gut–vascular barrier controls the systemic
dissemination of bacteria. Sci. [Internet]. 2015; 350(6262):830–
834. doi: https://doi.org/f3ptnf
[33] Drastich P, Honsová E, Lodererová A, Jarešová M, Pekáriková
A, Hoffmanová I, Sánchez D. Celiac disease markers in patients
with liver diseases: A single center large scale screening study.
World J. Gastroenterol. [Internet]. 2012; 18(43):6255–6262. doi:
https://doi.org/f4fn3h
but not gliadin antibodies predict coeliac disease in patients
with chronic liver disease. Scand. J. Gastroenterol. [Internet].
1997; 32(11):1162–1167. doi: https://doi.org/ff2gcc
[35] Green PHR, Cellier C. Celiac disease. N. Engl. J. Med. [Internet].
2007; 357(17):1731–1743. doi: https://doi.org/csbng2
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34351
9 of 9
pattern in young children with screening detected coeliac
disease. Clin. Exp. Immunol. [Internet]. 2015; 179(2):230–235.
doi: https://doi.org/f25bw8
MV, McMahon RP, Eaton WW. Randomized controlled trial
of a gluten–free diet in patients with schizophrenia positive
for antigliadin antibodies (AGA IgG): a pilot feasibility study.
J. Psychiatry Neurosci. [Internet]. 2019; 44(4):269–276. doi:
https://doi.org/gg892m
[38] Vojdani A. Detection of IgE, IgG, IgA and IgM antibodies against
raw and processed food antigens. Nutr. Metab. [Internet]. 2009;
6(1):1–17. doi: https://doi.org/b7cg6w
on renal NF–κ
experimental diabetic rats. Iran J. Basic Med. Sci. [Internet].
2023; 26(10):1–6. doi: https://doi.org/mjs8
[40] Himmerich H, Patsalos O, Lichtblau N, Ibrahim MA, Dalton B.
Cytokine research in depression: principles, challenges, and
open questions. Front. Psychiatry. [Internet]. 2019; 10(30):1–16.
doi: https://doi.org/ggxb38
[41] Halstensen TS, Brandtzaeg P. Activated T lymphocytes in the
α/β
α/β and
γ/δ cells in the epithelium. Eur. J. Immunol. [Internet]. 1993;
23(2):505–510. doi: https://doi.org/cksgvv
TO, Sollid LM. Immunobiology and immunopathology of human
gut mucosa: humoral immunity and intraepithelial lymphocytes.
Gastroenterol. [Internet]. 1989; 97:1562–1584. doi: https://doi.
org/mjs9
P. Gluten specific, HLA–DQ restricted T cells from coeliac
by interferon gamma. Gut. [Internet]. 1995; 37(6):766–776. doi:
https://doi.org/fpz6c8
[44] Risnes LF, Eggesbø LM, Christophersen A, Sollid LM. Response to:
“Some considerations about γδ and CD8+ T–cell responses in blood
after gluten challenge in treated celiac disease”. Mucosal Immunol.
[Internet]. 2021; 14(5):1216–1217. doi: https://doi.org/gkhf8s
a randomized, double–blind, 2–dose gluten challenge trial.
Gastroenterol. [Internet]. 2021; 160(3):720–733. doi: https://
doi.org/mjtb
of CD3 and CD8 receptors in the small intestine in male rats.
Braz. Arch. Biol. Technol. [Internet]. 2021; 64:e21210256. doi:
https://doi.org/mjtc
