Rat Duodenum Research Articles

Subacute and subchronic methomyl exposure induced toxic effects on intestines via oxidative stress in male albino rats: biochemical and histopathological study

The aim of the present study was to estimate the potential toxic effects of a subacute and a subchronic exposure to methomyl (MET) on some parts of the digestive system in male albino rats. Wistar rats were exposed daily by oral gavage to 4 mg/kg body weight (b.w.) of MET over 28 days in subacute experiments and to 1 mg/kg b.w. of MET for 90 consecutive days in subchronic exposure. Plasma levels of liver function indicators (ALT, AST, ALP and LDH) were significantly elevated after administration of MET to rats. MET had significant pro-oxidative effects on the intestines, as indicated by decreases in nonenzymatic (GSH) and enzymatic antioxidant (GPx, GST and CAT) parameters and significant increases in TBARS levels in both the duodenum and colon of rats. Microscopically, the duodenum and colon of rats exposed to MET showed severe pathological changes. It could be concluded that MET profoundly altered the structure and antioxidant status of intestinal rat tissue, which might lead to intestinal and digestive dysfunctions.

A Novel Biodegradable Tubular Stent Prevents Pancreaticojejunal Anastomotic Stricture

Stricture of pancreatic-enteric anastomoses is a major late complication of a pancreaticoduodenectomy for the treatment of a periampullary tumor and can lead to exocrine and endocrine insufficiency such as malnutrition and diabetes mellitus. We investigated the safety and efficacy of a biodegradable tubular stent (BTS) for preventing a pancreaticojejunostomy (PJ) anastomotic stricture in both a rat and porcine model. The BTS was manufactured using a terpolymer comprising poly p-dioxanone, trimethylene carbonate, and glycolide. A cohort of 42 rats was randomized into 7 groups of 6 animals each after BTS placement into the duodenum for the biodegradation assay. A total of 12 pigs were randomized equally into a control and BTS placement group. The effectiveness of the BTS was assessed by comparing radiologic images with histologic results. Surgical procedures and/or BTS placements were technically successful in all animals. The median mass losses of the removed BTS samples from the rat duodenum were 2.1, 6.8, 11.2, 19.4, 26.1, and 56.8% at 1, 2, 3, 4, 6, and 8 weeks, respectively. The BTS had completely degraded at 12 weeks in the rats. In the porcine PJ model, the mean luminal diameter and area of the pancreatic duct in the control group was significantly larger than in the BTS group (all p < 0.05). BTS placement thus appears to be safe and effective procedure for the prevention of PJ anastomotic stricture. These devices have the potential to be used as a temporary stent placement to treat pancreatic-enteric anastomoses, but further investigations are required for optimization in human.

Biodegradable polymer-nanoclay composites as intestinal sleeve implants installed in digestive tract for obesity and type 2 diabetes treatment.

Obesity and type 2 diabetes have become serious health problems in 21st century. Development of non-invasive treatment to treat obesity and type-2 diabetes is still unmet needs. For targeting on this, one of the promising treatments is to implant an intestine sleeve in the gastrointestinal tract for limitation of food absorption. In this context, biodegradable polymer intestine sleeve was composed of polycaprolactone (PCL), poly-DL-lactic acid (PDLLA) and disk-shape nano-clay (Laponite®), and fabricated as an implantable device. Here, Laponite® as a rheological additive to improve the compatibility of PCL and PDLLA, and the polymers/clay composites were also evaluated by scanning electron microscopy SEM analysis and mechanical measurements. The mass ratio 90/10/1 of PCL/PDLLA/Laponite® composite was selected for fabrication of intestine sleeve, because of the highest toughness and flexibility, which are tensile strength of 91.9N/mm2 and tensile strain of 448% at the failure point. The prepared intestine sleeve was implanted and deployed at the duodenum in type2 diabetic rats, providing significant benefits in control of the body weight and blood glucose, while compared with the non-implanted type 2 diabetic rats. More importantly, the food intake records and histopathological section reports presented that the implanted rats still have normal appetites and no noticeable acute symptoms of inflammation in the end of the test. These appreciable performances suggested the implantation of biocompatible polymer composites has a highly potential treatment for obesity and type 2 diabetes.

Исследование иннервации двенадцатиперстной кишки крысы с использованием нейральных иммуногистохимических маркеров

The purpose of the work is to study the topography, morphology, and mediator status of the nerve apparatus of the rat duodenum using immunohistochemical methods. The use of markers selective for the peripheral nervous system (PGP 9.5, synaptophysin (Syn), serotonin (5HT) and tyrosine hydroxylase (TH) made it possible to reveal in the tissues of the intestinal wall, in addition to the two main submucosal and myienteral ganglionic nerve plexuses), the third plexus is the mucous epithelium villous. Using comparative immunohistochemical analysis, it was found that most of the nerve structures (neurons, nerve fibers, interneuronal and neuromuscular synapses in the ganglion plexuses) are PGP 9.5-immunopositive and cholinergic. There are no catecholaminergic and serotonergic (5HT +) neurons in the studied ganglion plexuses. It is assumed that postganglionic sympathetic fibers enter the duodenum from the outside. They participate in the innervation of the muscle layers of the intestinal wall and arterial vessels, form pericellular synapses on the bodies and dendrites of parasympathetic neurons. A large number of terminal varicose axons were found in the connective tissue of the villi using PGP 9.5, and single bipolar neuron-like cells were found in the epithelium. Sympathetic elements in the villi were not identified. A reaction to serotonin revealed a large number of serotonin-containing cells that were morphologically similar to enterochromaffinocytes.

Metabolic response to dietary supplementation with iron and folic acid in the rat

AbstractFolic acid (FA) and iron absorption is performed by transporters encoded by the Slc46a1 and Slc11a2 genes, respectively. The aim of this study was to determine how FA and iron deficiency in rats, and subsequent supplementation of the animals’ diet with these nutrients, affects Slc11a2 and Slc46a1 gene expression and the metabolic biomarkers of FA and iron status.150 female Wistar rats were assigned to a group fed a diet deficient in iron and FA (D, n = 120) or to a group fed a control diet (C, n = 30, AIN-93M) for 28 days. After this period, the rats were randomized to a group fed for 2, 10, or 21 days with a diet deficient in FA and supplemented with iron (DFE), a diet deficient in iron and supplemented with FA (DFOL), a diet supplemented with iron and FA (FEFOL), or a diet deficient in iron and folic (D).Transcript and protein levels were determined in the duodenum using the real-time PCR and western blot methods, respectively. FA concentrations in serum were assessed using the electrochemiluminescence method, and homocysteine concentrations were determined with an enzymatic assay. Iron metabolism was evaluated by measuring the total and unsaturated iron-binding capacity (TIBC and UIBC) in serum, and iron concentrations were determined using a photometric method. Hepcidin concentrations were measured in plasma with an immunoenzymatic method. Morphological parameters of the blood were determined with a Sysmex XT-4000 analyzer.The D group had higher Slc11a2 transcript levels than the DFE group at every time-point (p &lt; 0.01). There were higher Slc46a1 mRNA levels in the DFE group than in the FEFOL group at the third time-point (p &lt; 0.05). We did not observe any differences in PCFT or DMT1 protein abundance. The DFOL, FEFOL, and C groups had higher serum FA concentrations at the second and third time-points (p &lt; 0.001), as well as the lowest homocysteine concentrations (p &lt; 0.001). TIBC concentrations were lowest in the DFE and the FEFOL groups at the final time-point (p &lt; 0.001). We did not observe any differences in hepcidin concentrations. Simultaneous supplementation with FA and iron resulted in significantly higher hemoglobin concentrations at the third time-point (p &lt; 0.01).This study shows that dietary FA and iron deficiency, and subsequent supplementation with moderate amounts of these nutrients, may affect the transcription but not the protein abundance of FA and iron transporters in the rat duodenum.

Influence of magnesium hydroxide nanoparticles on the ultrastructural characteristics of the duodenum of Non-linear albino white rats

Influence of magnesium hydroxide nanoparticles on the ultrastructural characteristics of the duodenum of Non-linear albino white rats

Reactive Changes of Endocrine Cells of Intestinal Mucosal Epithelium with Administration of Melatonin or Doxylamine Succinate (Electron Microscopic Study)

Using an electron microscopy method, the structure of endocrinocytes of mucosal epithelium of duodenum, colon, and rectum in Wistar line rats was studied after daily administration of melatonin or doxylamine succinate for 1 month. It was demonstrated that morphological traits of increased functional activity (which is often accompanied by intracellular regeneration phenomena) are observed 1 day after the last administration of the studied substances. Mitochondria of endocrinocytes are primarily subject to changes. In addition, a large number of poorly differentiated endocrine cells were registered in the intestinal epithelium of rats subjected to experimental exposure, which indicates the activation of cambial elements of the epithelium. In all studied cases, D1 cells were more frequently found in the epithelium than other types of endocrinocytes.

Stimulation of gastroduodenal HCO3- secretion by lubiprostone mediated by different prostaglandin EP receptor subtypes

We examined the stimulatory effects of lubiprostone, a bicyclic fatty acid derived from prostaglandin E1 and a chloride channel type-2 opener (ClC-2), on HCO3- secretion in the rat stomach and duodenum, with a focus on the EP receptor subtypes involved in this action. Under urethane anesthesia, an ex-vivo chambered stomach or a duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH stat-method. Lubiprostone (0.1–30 μM) was perfused in the chamber or loop for 10 min. Indomethacin, ONO-8711 (an EP1 antagonist), or AE5-599 (an EP3 antagonist) was given s.c. 1 h before the lubiprostone treatment, while AE3-208 (an EP4 antagonist) or CFTRinh-172 (a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor) was given i.p. 30 min before. Lubiprostone dose-dependently and significantly increased HCO3- secretion in both the stomach (≥ 10 μM) and duodenum (≥ 1 μM). The stimulatory effect in the stomach was significantly abrogated by a pretreatment with the EP1 antagonist, but not the EP3/EP4 antagonists or CFTR inhibitor, while that in the duodenum was significantly attenuated by the EP3/EP4 antagonists as well as the CFTR inhibitor. Indomethacin had no effect on the response of either tissue to lubiprostone. These results suggest that lubiprostone stimulated HCO3- secretion in the stomach and duodenum in a manner that was mediated by different EP receptor subtypes; the former was mediated by EP1 receptors, while the latter was mediated by both EP3 and EP4 receptors. CFTR/ClC-2 may be involved in the response observed in the duodenum, but not in the stomach.

Antiulcerogenic Activity of Li-Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR-2/MyD88 Signaling Pathway.

Background Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) often causes small intestinal ulcers in patients, but few effective drugs are currently available to manage such serious adverse events of NSAIDs. Li-Zhong decoction (LZD), a well-known traditional Chinese medicine (TCM) formula, is commonly prescribed for treatment of gastrointestinal diseases. The present study aimed to investigate the anti-ulcerogenic activity of LZD on indomethacin- (IND-) induced duodenal ulcer in rats. Mechanistic studies of action of LZD were focused on involvement of TLR-2/MyD88 signaling pathway. Methods Fifty male Sprague-Dawley (SD) rats were randomly and evenly divided into five groups: normal control, ulcer control (IND, 25 mg/kg), IND + esomeprazole (ESO, 4.17 mg/kg), and IND + low and high doses of LZD (3.75 and 7.50 g/kg). Macroscopic and histopathological examinations were performed for evaluation of ulcer index (UI), curative index (CI), and microscopic score (MS). Levels of duodenal inflammatory biomarkers and cytoprotective mediators including interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α (TNF-Results Gross and microscopic examinations of the IND-treated rats revealed severe duodenal hemorrhagic necrosis, inflammatory infiltration, villus destruction, and crypt abscess, while LZD-treated rats manifested these pathological events to a markedly lesser degree. LZD significantly decreased UI and MS, increased CI, preserved the integrity of the villus and crypt, and normalized the tissue architecture of the duodenum of rats. The elevated TNF-α (TNF-Conclusions Our data demonstrate that LZD protects the duodenal mucosa from IND-caused lesions, which is at least partially attributable to the interaction of its potential cytoprotective and anti-inflammatory mechanisms together with enhancement of the mucosal immunity through TLR-2/MyD88 signaling pathway.

Histomorfometric Analysis of Duodenum of Rats Submitted to Food Stress

Histomorfometric Analysis of Duodenum of Rats Submitted to Food Stress

Modified Liu-Jun-Zi decoction alleviates visceral hypersensitivity in functional dyspepsia by regulating EC cell-5HT3r signaling in duodenum.

Modified Liu-Jun-Zi (MLJZ) is derived from one of the most famous traditional Chinese prescription Liu-Jun-Zi. It exhibits therapeutic effects in functional dyspepsia (FD), but the underlying mechanisms remain not well understood. Enterochromaffin (EC) cells contribute to the pathogeneses of visceral hypersensitivity in functional gastrointestinal disorders. But whether and how EC cells in duodenum participate in the mechanism of FD remain unsettled. To detect the crucial factors related to EC cells, and to evaluate the therapeutic effect of MLJZ and to determine whether MLJZ relieves visceral hypersensitivity in FD by regulating EC cell-5-hydroxytryptamine 3 receptor (5HT3r) signaling. FD rats were established by iodoacetamide gavage combined with tail clamping method. The verification of FD model and the evaluation of the therapeutic effect of MLJZ was taken place by hematoxylin-eosin (HE) staining and visceral sensitivity measurement. The expression of EC cells and 5-hydroxytryptamine (5HT) in duodenum was detected by Immunohistochemistry (IHC) staining and enzyme-linked immunosorbent assay (ELISA). IHC staining and quantitative polymerase chain reaction (qPCR) were applied to measure the expression of tryptophan hydroxylase-1 (TPH1), paired box gene 4 (PAX4), transient receptor potential A1 (TRPA1), transient receptor potential C4 (TRPC4) and 5HT3r. Duodenum sections were stained by double immunofluorescence (IF) to study the synthesis of 5HT in EC cells. The gastric sensitivity increased in FD rats while MLJZ decoction significantly attenuated visceral hypersensitivity. The duodenum of FD rats displayed increased expressions of EC cells, 5HT, TPH1, PAX4 and 5HT3r. And the overexpression was reduced in response to MLJZ decoction treatment. EC cell-5HT3r signaling pathway is abnormally active in FD with visceral hypersensitivity. And MLJZ decoction can alleviates visceral hypersensitivity in FD by regulating EC cell-5HT3r signaling in duodenum.

How motility can enhance mass transfer and absorption in the duodenum: Taking the structure of the villi into account

Given the complex motility of the intestinal wall featuring villous structure, the mechanisms by which the motility can enhance mass transfer and absorption in the small intestine have been a mystery. In this work, the challenging task to couple the intestinal lumen flow and the contraction movement of the villi is tackled by a multi-physics model. The effects of motility of an entire duodenum on the mass transfer and absorption under the influence of ambient flow can be systematically explored. It is revealed that the top of the villi plays a major role in mass absorption. For a rat duodenum, the pendular movement can enhance mass transfer and absorption by up to about 72%. With the introduction of ambient flow, although the absorption amount increases, the enhancement of mass transfer by pendular activity is inhibited. Specifically, the average enhancement factor decreases sharply from ~1.35 to ~1.05.

Age related changes of neuropeptide Y-ergic system in the rat duodenum

Neuropeptide Y (NPY) is widely distributed in the autonomic nervous system and acts as a neurotransmitter and a trophic factor. However, there is no report concerning the expression of NPY and its receptors in the intestine during postnatal ontogenesis. In the current study, immunohistochemistry and western blot analysis was used to label NPY, Y1R, Y2R and Y5R receptors in the duodenum from rats of different ages (1-, 10-, 20-, 30-, 60-day-old and 2-year-old).The obtained data suggest age-dependent changes of NPY-mediated gut innervation. NPY-immunoreactive (IR) neurons were observed in the myenteric (MP) and submucous (SP) plexus from the moment of birth. In the MP, the percentage of NPY-IR neurons was low and varied from 4.1 ± 0.32 in 1-day-old to 2.9 ± 0.62 in 2-year-old rats. The proportion of NPY-IR myenteric neurons did not change significantly through the senescence (p > .05). In the SP, the proportion of NPY-IR neurons significantly increased in the first month of life from 56.3 ± 2.4% in 1-day-old to 78.1 ± 5.18% in 20-day-old and significantly decreased from 75.6 ± 4.62% in 30-day-old rats to 59.8 ± 4.24% in 2-year-old rats.The expression of NPY in the duodenum did not change significantly during the development by western blot analysis. The expression of Y1R and Y2R was low in newborns and upregulated in the first ten days of life. The expression of Y5R was maximal in newborn pups and significantly decreased in in the first 20 days.Thus, there are some fluctuation of the percentage of NPY-IR neurons accompanies changes in relation of different subtypes of NPY receptors in the small intestine during postnatal ontogenesis.

Enterohepatic Circulation and Pharmacokinetics of Genistin and Genistein in Rats.

Genistin and its aglycone genistein of isoflavone are naturally occurring in plants. The aim of this study is to develop an experimental animal model of enterohepatic circulation to investigate the metabolic biotransformation of genistin and genistein in rats. A paired-rat model was developed in which the drug was administered intravenously to the donor rat whose bile duct was cannulated into the duodenum of the untreated recipient rat. The blood sample was collected from the jugular vein of the donor and recipient rats after genistin administration. The results demonstrate that genistein was detected in both the donor and recipient rats after genistein administration (50 mg/kg, iv) in the donor rat, which suggested that the enterohepatic circulation of genistein occurred. The same phenomenon happened again in the biotransformation after genistin administration (50 mg/kg, iv) in the donor rat. Genistein was detected in the recipient rat’s blood sample after treatment with β-glucuronidase, which suggested that enzymatic hydrolysis occurred in the transformation of genistin into genistein. In conclusion, the research revealed the metabolic pathway of the glucuronidation of genistin into genistein.

Gastrointestinal effects of standardized Brazilian phytomedicine (Arthur de Carvalho Drops®) containing Matricaria recutita, Gentiana lutea and Foeniculum vulgare

Arthur de Carvalho Drops® (ACD) is a traditional Brazilian herbal medicine used to treat functional gastrointestinal disorders (FGIDs). ACD is a formulation of herbal extracts from Matricaria recutita (chamomile), Foeniculum vulgare (fennel) and Gentiana lutea L. (gentian). Considering the popular use for FGIDs, the aim of this work was to investigate the ACD effect on gastric and intestinal parameters with emphasis in a mechanistic approach using isolated duodenal preparations of rodents. Analytical method was developed and validated for quantify three actives principles/markers (Apigenin-7-glucoside, gentiopicroside and anethole) in ACD. The treatment with ACD significantly reduced the emetogenic stimuli induced by cisplatin in rats, showed a laxative effect, reduced the bethanechol-enhanced gastrointestinal transit and completely reversed the contraction induced by carbachol in rat duodenum. However, ACD did not alter the secretory gastric volume or total gastric acidity. The ACD affect the contractions of duodenal smooth muscle mediated by Ca2+ channels and it is also able to inhibit the contractile response mediated by the release from its intracellular store. Furthermore, the relaxant effects of ACD appear independent of the nitric oxide pathway in rat duodenum. These results suggest that ACD could be beneficial for the treatment of disorders of the gastrointestinal tract.

Effect of processing on the in vitro digestion characteristics of oat products by using a dynamic rat stomach-duodenum model

This study investigated the in vitro digestive behavior of different processed oat products using a dynamic rat stomach and duodenum model. The changes in gastric emptying with respect to digestion time, glucose concentration, estimated glycemic index (GI), rheological and microstructural properties of the gastric and duodenal digests were determined. The results showed that the digesta viscosity of oatmeal (OM), oat wowo (OW), oat paste (OP) and oat rice (OR) decreased faster than unprocessed oat (UO) during digestion. Glucose concentration and gastric emptying increased with decreasing viscosity of oat products digesta at each digestion time. OR and OP had a higher gastric emptying rates and glucose concentration as compared to UO, OM and OW. The estimated GI of UO, OM and OW were lower than 55 and belonged to low GI food. The porous structures of oat products observed indicated that thermal treatments can change the digestion characteristics of oat products.

Structural changes of the intestinal epithelial barrier of the duodenum of rats in burn injury of skin under experimental streptozotocin-induced diabetes mellitus

The aim of the study was to study the structural changes of the intestinal epithelial barrier in the duodenum in burn injury of skin in rat under experimental streptozotocin-induced diabetes mellitus. The study was carried out on laboratory white adult rats-males weighing 180-210 g. The control group consisted of 21 animals without somatic pathology, the first experimental group was 21 rats with burn skin injury, the second experimental group was 21 rats with burn skin and experimental streptozotocin-induced diabetes mellitus. The experimental diabetes model was reproduced by administering streptozotocin to the rats intraperitoneally at a single dose of 50 mg/kg. Thermal burn skin damage in rats corresponded to II – A-B degrees of dermal surface burn (according to the old classification III – A degree) with a total area of 21-23 % of the body surface with the development of burn shock. Duodenum was selected for morphological studies, fragments of which were processed by conventional methods of light and electron microscopy. The main criteria for assessing damage to the duodenal mucosa enterocytes were the results of a study comparing histological and ultrastructural data in dynamics at 7, 14, and 21 days after skin burns. The results of the studies showed that the base of damage to the intestinal epithelial barrier of the duodenum are deep destructive changes, which after 21 days (in the stage of septicotoxemia), as a rule, are not reverse and develop on the background of significant intoxication of the body. There was a decrease in the number of tight junctions in the intestinal epithelial barrier of the duodenum of rats of the first and second experimental groups and a loss of ordering (acquisition of some chaotic nature) of their localization as the time after burn injury increased. For the most part, the intestinal epithelial barrier loses the integrity of the cellular component with partial preservation of the basement membrane (the first occurs both due to necrosis of the enterocytes with a brush border and due to complete destruction of goblet cells). In all cases, defects exist in the intestinal epithelial barrier, which are potential pathways for paracellular translocation of the pathogenic contents of the duodenum. It is not inconceivable that part of this intestinal pathogenic content can be translocated also by partially damaged cells. Evidence of the latter is the presence of microbial bodies in the cytoplasm of cells with partially destroyed plasmalemma (but preserved organelles and nucleus). An adaptive mechanism for ensuring the repair of damaged enterocytes is selective autophagy, which acts as a factor in the recycling of destroyed organelles and the cytoplasmic matrix, aimed primarily at maintaining cell viability.

Spasmolytic Effects of Salvia triloba Leaf Extract on Smooth Muscles of the Duodenum in Rats

Spasmolytic Effects of Salvia triloba Leaf Extract on Smooth Muscles of the Duodenum in Rats

Intestinal Inflammation Differentially Influences Iron Homeostasis in WT versus Hepcidin KO Rats

IntroductionThe chronic anemia associated with IBD in humans may result from trans‐activation of the the iron‐regulatory hormone (Hamp) by pro‐inflammatory cytokines in hepatocytes. High hepcidin decreases serum iron by blunting intestinal iron absorption and impairing release of storage iron, thus decreasing iron delivery to the erythroid marrow and causing anemia. Pharmacological targeting of hepcidin offers an attractive therapeutic approach to mitigate IBD‐associated anemia. Testing of such interventions has mainly utilized mouse models of hereditary hemochromatosis (HH). Collectively, these mice have inappropriately low (or absent) hepcidin expression, and concomitant increases in intestinal iron absorption leading to iron overload. However, since iron metabolism in mice and humans varies notably, development of complementary experimental models is imperative.ObjectiveWe created a novel model of HH, the Hamp KO rat, and utilized the DSS model of colitis for this investigation. We hypothesized that Hamp levels would increase in rats with colitis (due to pro‐inflammatory cytokine signaling), which would then blunt intestinal iron absorption and cause anemia (thus modeling human IBD). We further postulated that iron absorption would be unaffected by inflammation in Hamp KO rats, thus preventing the development of anemia.MethodsIntestinal inflammation was induced by providing DSS (4% w/v) in drinking water for 7 days. Standard bioassays were utilized to track iron loading. Iron absorption was assessed by oral‐intragastric gavage of an 59Fe transport solution.ResultsHamp−/− rats displayed multi‐visceral iron overload, and intestinal iron absorption was increased (≈2.5 fold). DSS treatment caused similar pathological changes in the duodenum and colon of Hamp KO rats and WT littermates. Systemic inflammation was not observed in any experimental animals. DSS exposure decreased TSAT, and serum and splenic nonheme iron in both genotypes. In WT animals, DSS exposure: 1) decreased blood hemoglobin levels by ≈15%; 2) reduced liver hepcidin expression by ≈60%; 3) and increased intestinal iron absorption by &gt;2‐fold. Conversely, in Hamp−/− rats, DSS treatment increased blood hemoglobin levels and decreased iron absorption by ≈2.5‐fold. Moreover, the distribution of absorbed 59Fe in blood and many tissues was different between genotypes after DSS txt.ConclusionsDespite the lack of systemic inflammation, iron homeostasis was perturbed in WT rats by DSS‐induced enteritis. Reduced hepcidin expression likely resulted from anemia and/or iron depletion of serum and spleen. This may explain why iron absorption increased, since a relative state of iron deficiency may have existed after DSS exposure. In the KOs, intestinal inflammation altered iron homeostasis in distinct ways. This differential response to DSS may relate to the iron‐overload phenotype of the KO rats, or alternatively, it could reflect a role for hepcidin in mediating the pathophysiologic response to intestinal inflammation. Future studies in iron‐depleted Hamp KO rats may allow for a better understanding of the role of hepcidin in regulating iron homeostasis in IBD.Support or Funding InformationNIH Grant R01 DK074867 and R01 DK109717 (to JFC)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

СТРУКТУРНІ ОСОБЛИВОСТІ СЛИЗОВОЇ ОБОЛОНКИ ДВАНАДЦЯТИПАЛОЇ КИШКИ ЩУРІВ ПРИ ОПІКОВІЙ ТРАВМІ ШКІРИ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО СТРЕПТОЗОТОЦИНІНДУКОВАНОГО ЦУКРОВОГО ДІАБЕТУ

Робота присвячена вивченню структурних особливостей слизової оболонкидванадцятипалої кишки при опіковій травмі шкіри за умов експериментальногострептозотоциніндукованого цукрового діабету. Дослідження здійснене на лабораторнихбілих статевозрілих щурах-самцях масою 180-210 г. Групу контролю склали 21 інтактнатварина, І експериментальну групу склали 21 щур з експериментальною опіковою травмоюшкіри, ІІ експериментальну групу склали 21 щур без опіку шкіри з експериментальнимстрептозотоциніндукованим діабетом, ІІІ експериментальну групу склали 21 щур з опікомшкіри та експериментальним стрептозотоциніндукованим діабетом. Модельекспериментального цукрового діабету відтворювали шляхом введення щурамстрептозотоцину внутрішньоочеревенно одноразово в дозі 50 мг/кг. Термічне опіковепошкодження шкіри у щурів відповідало II – А-Б ступеню – дермального поверхневого опіку (застарою класифікацією III – А ступінь) загальною площею 21-23% поверхні тіла з розвиткомопікового шоку. Для морфологічних досліджень було забрано відділ дванадцятипалої кишки,фрагменти якого обробляли загальноприйнятими методами світлової та електронноїмікроскопії. Основними критеріями оцінки пошкодження слизової оболонки дванадцятипалоїкишки стали результати дослідження щодо порівняння гістологічних та ультраструктурнихданих в динамиці через 7, 14, та 21 добу після опіку шкіри. Результати проведених дослідженьпоказали зменшення кількості щільних контактів в інтестінальному епітеліальному бар’єріслизової оболонки дванадцятипалої кишки щурів першої та третьої експериментальних групта втрату упорядкованості (набуття певної хаотичності) їхньої локалізації у міру збільшеннячасу після опікової травми. В інтестінальному епітеліальному бар’єрі з’являються дефекти,які є потенційними шляхами парацелюлярної транслокації патогенного вмістудванадцятипалої кишки. Не виключно, що частина цього інтестінального патогенного вмістуможе бути транслокована і через частково пошкоджені клітин. Свідченням останнього євиявлена наявність мікробних тіл в цитоплазмі клітин з частково зруйнованою плазмолемою(але збереженими органелами та ядром). Адаптивним механізмом щодо забезпечення репараціїушкоджених ентероцитів є селективна автофагія, яка виступає чинником рециклізаціїматеріалу зруйнованих органел і цитоплазматичного матриксу, спрямованого, в першу чергу,на підтримку життєздатності клітин. Ініціація автофагії асоційована з розвитком вентероцитах стресу ендоплазматичного ретикулуму (ER-стресу). В ентероцитахдванадцятипалої кишки щурів третьої експериментальної групи ER-стрес відбуваєтьсянастільки стрімко і супроводжується неухильним поширенням процесів деструкції в клітині,що механізми автофагії не встигають спрацьовувати і більшість клітин гине. Таким чином,відсутність автофагійної реакції є маркером несприятливого спрямування перебігупісляопікових структурних змін в ентероцитах.