Rat Small Intestine Research Articles

Antispasmodic, cardioprotective and blood-pressure lowering properties of Gomphrena perennis L. and its mechanisms of action

BackgroundGomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet. AimTo evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved. Experimental procedureThe chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats. ResultsFifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery. ConclusionsThis study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

1,2-bis(2,4,6-tribromophenoxy) ethane, a novel brominated flame retardant, disrupts intestinal barrier function via the IRX3/NOS2 axis in rat small intestine

Novel brominated flame retardants are widely used in electronics, textiles, furniture, and other products; they can enter the human body through ingestion and respiration and cause harm to the human body, and have been proven to have potential biological toxicity and accumulation effects. 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) is a widely used novel brominated flame retardant; however, there is a lack of research on its mechanism of toxicity, particularly that of intestinal toxicity. Currently, studies on the functionality of iroquois homeobox 3 (IRX3) are extremely limited. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat small intestinal crypt epithelial cells (IEC6 cells) in vivo and in vitro, respectively, and hematoxylin and eosin (HE), immunohistochemical, Alcian blue-periodic acid-Schiff (AB-PAS), CCK8, acridine orange/ethidium bromide (AO/EB), fluorescent probes, qPCR, western blotting, and immunofluorescence analyses were performed. To explore the damage mechanism of BTBPE, we used siRNA to silence IRX3 and iNOs-IN-1 (yeast extract-peptone-wheat; YPW) to inhibit nitric oxide synthase 2 (NOS2). The results showed that BTBPE exposure caused inflammation and necroptosis in the jejunum and ileum, as well as destruction of the tight junctions and mucus layer. Moreover, BTBPE activated the IRX3/NOS2 axis both in vivo and in vitro. Silencing IRX3 or inhibiting NOS2 inhibits necroptosis and restores tight junctions in IEC6 cells. In conclusion, our study found that in the jejunum, ileum, and IEC6 cells, BTBPE exposure caused necroptosis and tight junction destruction by activating the IRX3/NOS2 axis. Blocking the IRX3/NOS2 axis can effectively inhibit necroptosis and restore tight junction. In addition, BTBPE exposure caused inflammation and loss of the mucous layer in the jejunum and ileum. Our study is the first to explore the mechanism of intestinal damage caused by BTBPE exposure and to discover new biological functions regulated by the IRX3/NOS2 axis, providing new research directions for necroptosis and tight junctions.

Gastrointestinal metabolism characteristics and mechanism of a polysaccharide from Grifola frondosa

Grifola frondosa polysaccharide (GFP) is mainly composed of α-1,4 glycosidic bonds and possesses multiple pharmacological activities. However, the absence of pharmacokinetic studies has limited its further development and utilization. Herein, GFP was labeled with 5-DTAF (FGFP) and cyanine 5.5 amine (GFP-Cy5.5) to investigate its gastrointestinal metabolism characteristics and mechanism. Significant distributions of the polysaccharide in the liver and kidneys were observed by near infrared imaging. To investigate the specific distribution form of the polysaccharide, in vitro digestion models were constructed and revealed that FGFP was degraded in saliva and rat small intestine extract. The metabolites were detected in the stomach and small intestine, followed by further degradation in the distal intestine in the in vivo experiment. Subsequent investigations showed that α-amylase was involved in the gastrointestinal degradation of GFP, and its metabolite finally entered the kidneys, where it was excreted directly with urine.

Endotoxin induced acute kidney injury modulates expression of AQP1, P53 and P21 in rat kidney, heart, lung and small intestine.

This study was designed to explore whether aquaporin 1(AQP1), P53 and P21 can be used as diagnostic biomarkers of lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and potential indicators of sepsis-induced multiple organ injury. Bioinformatics results demonstrated that AQP1, P53, P21 was dramatically elevated 6h after Cecal ligation and puncture (CLP)-AKI in rat renal tissue. The expression of AQP1, P53, P21, NGAL and KIM-1 in kidney were increased significantly at first and then decreased gradually in LPS-induced AKI rats. Histopathological sections showed swelling of tubular epithelial cells and destruction of basic structures as well as infiltration of numerous inflammatory cells in LPS-induced AKI. Moreover, the expressions of AQP1, P53 and P21 in heart were significantly increased in LPS treatment rats, while the AQP1 expressions in lung and small intestine were significantly decreased. The level of NGAL mRNA in heart, lung and small intestine was firstly increased and then decreased during LPS treatment rats, but the expression of KIM-1 mRNA was not affected. Therefore, our results suggest that AQP1, P53 and P21 is remarkably upregulated in LPS-induced AKI, which may be considered as a potential novel diagnostic biomarker of Septic AKI. NGAL may serve as a biomarker of sepsis-induced multiple organ damage during the process of LPS-induced AKI.

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading.

During acute base excess, the renal collecting duct β -intercalated cells ( β -ICs) become activated to increase urine base excretion. This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFTR) expressed in the apical membrane of β -ICs. The signal that leads to activation of this process was unknown. Plasma secretin levels increase during acute alkalosis, and the secretin receptor (SCTR) is functionally expressed in β -ICs. We find that mice with global knockout for the SCTR lose their ability to acutely increase renal base excretion. This forces the mice to lower their ventilation to cope with this challenge. Our findings suggest that secretin is a systemic bicarbonate-regulating hormone, likely being released from the small intestine during alkalosis. The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β -intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β -intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid-base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.

GC-MS, alpha-amylase, and alpha-glucosidase inhibition and molecular docking analysis of selected phytoconstituents of small wild date palm fruit (Phoenix pusilla).

Phoenix pusilla (Arecaceae), commonly known as "small wild date palm", is regarded as one of the underutilized fruit crops in South India. Methanol extract of P. pusilla ripened fruits (PPRF) was analyzed for in vitro porcine pancreatic alpha-amylase (PPAA) and rat small intestine alpha-glucosidase (RIAG) inhibition activities, and through gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS analysis showed the presence of 25 phytoconstituents from PPRF which was further assessed on the docking behavior of five targeted enzymes diabetes mellitus (DM) namely (i) human aldose reductase, (ii) protein tyrosine phosphatase 1B, (iii) pancreatic alpha-amylase, (iv) peroxisome proliferator-activated receptor gamma, and (v) dipeptidyl peptidase IV by using the AutoDock Vina method. In addition to this physicochemical, bioactivity score, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was performed using the Molinspiration and pkCSM free online servers. Methanolic extract of PPRF showed 50% inhibition concentration (IC50) at 69.86 and 72.60 μg/mL levels against PPAA and RIAG enzymes activities, respectively. Interestingly in the present study, GC-MS analysis showed the presence of 25 phytoconstituents from PPRF. Physicochemical analysis of PPRF has exhibited that 13 ligands have complied well with Lipinski's Rule of Five (RoF). With regard to ADMET analysis, one ligand (9,12-octadecadienoic acid [Z,Z]) has predicated to possess both the hepatotoxicity (HT) and skin sensitization (SS) effect. The docking studies showed that 1-formyl-2,5-dimethoxy-6,9,10-trimethyl-anthracene exhibited the maximum atomic contact energy (ACE) for all the five target enzymes of DM. Thus, the current study suggested that the methanolic extract of PPRF and its phytoconstituents could be considered as potent antidiabetic agents.

Pharmacokinetics and tissue distribution of 12 major active components in normal and chronic gastritis rats after oral administration of Weikangling capsules

Ethnopharmacological relevanceWeikangling Capsules (WKLCs) have been used in the clinic for the treatment of gastrointestinal disorders for more than 30 years. However, the pharmacokinetic characteristics and tissue distribution of its major bioactive components in rats under different physiological and pathological conditions are unclear. Aim of the studyIn this study, we aimed to clarify the differences in pharmacokinetic parameters and tissue distribution of the major active components in WKLCs under physiological and pathological states. Materials and methodNormal and ethanol-induced chronic gastritis rats received 2.16 g/kg WKLCs by gavage, and urine, feces, plasma, and tissue (heart, liver, spleen, lung, kidney, stomach, and small intestine) samples were obtained. The active components in urine, feces and plasma were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). A rapid and sensitive analytical method, ultra-high-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP-MS/MS), was established and validated to clarify and compare the pharmacokinetics and tissue distribution of the major active components in normal and chronic gastritis rats. ResultsA total of 36 chemical components in the feces, urine, and plasma of chronic gastritis rats were identified by UHPLC-Q-TOF-MS/MS. Among them, 20 were the prototype components of WKLCs, and 16 were metabolites. The pharmacokinetic characteristics and tissue distribution of 12 prototype components were successfully analyzed by UHPLC-QTRAP-MS/MS. The pharmacokinetic results showed that the Cmax, AUC0-t, and AUC0-∞ of paeoniflorin, glycyrrhizic acid, and glycyrrhetinic acid were distinctly higher than those of the other components in normal and chronic gastritis rats. Compared to normal rats, the Cmax, AUC0-t, and AUC0-∞ of albiflorin, liquiritin apioside, liquiritin, isoliquiritin, ononin, isoliquiritigenin, dactylorhin A, and glycyrrhizic acid were significantly increased in chronic gastritis rats (P < 0.05), while the Cmax, AUC0-t and AUC0-∞ of militarine and liquiritigenin had significantly lower decreases in chronic gastritis rats (P < 0.05). The results of the tissue distribution showed that the 12 components were widely distributed in the heart, liver, spleen, lung, kidney, stomach, and small intestine of rats, of which the liver, kidney, stomach, and small intestine were the main accumulative organs. Compared with normal rats, the concentrations of 12 components in the liver, kidney, stomach, and small intestine of chronic gastritis rats were widely higher than those of normal rats at the same time points. ConclusionThe pharmacokinetic characteristics and tissue distribution of 12 active components of WKLCs were comprehensively characterized and elucidated in normal and chronic gastritis rats. These findings laid a solid foundation for revealing the pharmacodynamic material basis of WKLCs in treating gastrointestinal disorders.

ВЛИЯНИЕ МЕРОПЕНЕМА И ИМИЦЕНЕМА НА МИКРОБИОЦЕНОЗ И МОРФОЛОГИЮ ТОНКОГО КИШЕЧНИКА КРЫС

Background. Gut microbiota plays an important role in the human body, antimicrobial drugs intake being one of the main factors affecting microbiota composition. Antibiotics suppress normal intestinal microflora allowing for the growth and development of pathogenic flora. Objective. To study the effect of meropenem and imicenem on the microbiocenosis and morphology of the small intestine in rats. Material and methods. In an experiment on rats, we analysed the microbiocenosis of the large intestine after intraperitoneal administration of meropenem, imicinem and 0.9% NaCl, as well as examined samples of the small intestine. Results. In a comparative analysis of the control group with the meropenem and imicinem groups, there has been noted a decrease in the number of anaerobes in the meropenem group (8.6±0.14, p&lt;0.05) as compared with the control group (9.4±0.22, p&lt;0 .05) and the imicinem group (9.4±0.40, p&lt;0.05); the number of bifidobacteria decreased in the meropenem group (8.1±0.16, p&lt;0.05) in contrast to the control group (9.2±0.25, p&lt;0.05) and the imicinem group (9.2±0.41, p&lt;0.05). When compared with meropenem (3.8±0.44, p&lt;0.05), imicinem (4.9±0.20, p&lt;0.05) led to a greater growth of spore-forming anaerobes. In animals of the imicinem group, the histostructure of the jejunal mucosa was similar to the control group, while in the meropenem group, inflammatory changes in the stroma of the villi of the jejunal mucosa were observed. Conclusions. In a comparative analysis of carbapenem activity, it has been determined that these antibiotics both have a significant effect on the microbiocenosis of the large intestine and affect the mucous wall of the small intestine. These should be taken into account by clinicians in order to improve the effectiveness and safety of antibiotic therapy.

DSPE-PEG polymer enhanced berberine absorption specifically in the small intestine of rats through paracellular passway.

This study focuses on investigating the potential impact of DSPE-PEG polymers on intestinal absorption and related mechanism of berberine in rats. Effect of DSPE-PEG polymer on intestinal absorption of berberine was investigated with an in situ closed-loop method in rats. To confirm the safety of DSPE-PEG polymer, morphological observation of rat intestine and measurement of biological markers in the intestinal perfusion of rats was performed. Underling mechanism behind promoting action of DSPE-PEG polymer was explored from its impact on the P-gp function and tight junction using in vitro diffusion chamber system, Caco-2 monolayer cells and western blot. DSPE-PEG polymer demonstrated significant enhancement action on the berberine absorption in rats without any obvious membrane toxicity. DSPE-PEG polymer (1.0%, w/v) induced the most significant promoting effect on berberine absorption specifically in the small intestine of rats. Results of mechanistic studies revealed that DSPE-PEG polymer might not regulate intestinal P-gp function, but significantly down-regulated the expression of tight junction-related proteins, which accordingly led to loosening the tight junctions of intestinal epithelium cells, and consequently increased paracellular absorption of berberine in rats. DSPE-PEG polymer, as an excellent absorption enhancer, seems very promising in increasing oral bioavailability of berberine.

Essential oil of Sicilian Prangos ferulacea (L.) Lindl. and its major component, β−ocimen, affect contractility in rat small and large intestine

Ethnopharmacological relevancePrangos ferulacea (L.) Lindl is an Apiaceae plant, widely used in traditional medicine. Recently, chemical composition and biological activities of its essential oil (Prangroil) have been reported, but there are no studies on possible effects on intestinal contractility. Aims of the studyWe investigated the effects of essential oil Sicilian Prangoil on the contractility of rat small (duodenum) and large (colon) intestine and the related action mechanism. Materials and methodsResponses to Prangoil and to its major component β−ocimen in intestinal segments were assessed in vitro as changes in isometric tension. ResultsPrangoil, induced in duodenum, depending upon doses, contraction and/or muscular relaxation. Instead, in colon Prangoil only reduced the phasic contractions and induced muscular relaxation. β−ocimen, in both segments, produced only reduction of the spontaneous contractions without affecting basal tone. Prangoil contractile effects were abolished by ω-conotoxin, neural N-type Ca2+ channels blocker, atropine, muscarinic receptor antagonist, neostigmine, acetylcholinesterase (AChE) inhibitor, suggesting that Prangoil-induced contraction would be the result of an increase in neuronal cholinergic activity. Prangoil and β−ocimen inhibitory effects were unaffected by ω−conotoxin, L-NAME, blocker of the NO synthase, ODQ, soluble guanylate cyclase inhibitor, excluding involvement of neurotransmitter release or NO synthesis in the inhibitory effects. Potassium channel blocker did not affect Prangoil or β-ocimen inhibitory responses. Prangoil or β-ocimen inhibited the Ca2+ and high-KCl solution -induced contractions and the Carbachol-induced contractions in calcium free solution. ConclusionPrangoil affects the contractility of small and large intestine in rat, with regional differences, via potentiation of neural cholinergic activity, blockade of L-type voltage-gated calcium channel and reduction of Ca2+ release from the intracellular store. The Prangroil main components, β−ocimen, contributes to the inhibitory effects.

Intestinal absorption of D-fructose isomers, D-allulose, D-sorbose and D-tagatose, via glucose transporter type 5 (GLUT5) but not sodium-dependent glucose cotransporter 1 (SGLT1) in rats.

D-allulose, D-sorbose and D-tagatose are D-fructose isomers that are called rare sugars. These rare sugars have been studied intensively in terms of biological production and food application as well as physiological effects. There are limited papers with regard to the transporters mediating the intestinal absorption of these rare sugars. We examined whether these rare sugars are absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via GLUT type 5 (GLUT5) using rats. High-fructose diet fed rats, which express more intestinal GLUT5, exhibited significantly higher peripheral concentrations, Cmax and AUC0–180 min when D-allulose, D-sorbose and D-tagatose were orally administrated. KGA-2727, a selective SGLT1 inhibitor, did not affect the peripheral and portal vein concentrations and pharmacokinetic parameters of these rare sugars. The results suggest that D-allulose, D-sorbose and D-tagatose are likely transported via GLUT5 but not SGLT1 in rat small intestine.

Virome of wild rats (Rattus norvegicus) captured far from pig farms in Jiangsu province of China reveals novel porcine circovirus type 2d (PCV2d) sequences

BackgroundPorcine circovirus type 2 (PCV2) has caused great economic losses in the global pig industry. There have been published records of wild rats acting as the reservoirs of PCV2 (only PCV2a and PCV2b), but almost all of which were related to the PCV2-infected swine herds.ResultsIn this study, we carried out the detection, amplification, and characterization of novel PCV2 strains in wild rats that were captured far from pig farms. Nested PCR assay demonstrated that the kidney, heart, lung, liver, pancreas, and large and small intestines of rats were screened positive for PCV2. We subsequently sequenced two full genomes of PCV2 in positive sample pools, designated as js2021-Rt001 and js2021-Rt002. Genome sequence analysis indicated that they had the highest similarity to nucleotide sequences of porcine-origin PCV2 isolates in Vietnam. Phylogenetically, js2021-Rt001 and js2021-Rt002 were a part of the PCV2d genotype cluster, which is a predominant genotype circulating worldwide in recent years. The antibody recognition regions, immunodominant decoy epitope, and heparin sulfate binding motif of the two complete genome sequences coincided with those previously reported.ConclusionsOur research reported the genomic characterization of two novel PCV2 strains (js2021-Rt001 and js2021-Rt002) and provided the first supported evidence that PCV2d could naturally infect wild rats in China. However, whether the newly identified strains have potential for circulating in nature in vertical and horizontal transmission or inter-species jumping between rats and pigs needs further research.

Weight loss by calorie restriction does not alter appetite-regulating gut hormone responses from perfused rat small intestine.

Postprandial secretion of the appetite-inhibiting hormones, glucagon-like peptide-1 (GLP-1), and peptide YY are reduced with obesity. It is unclear if the reduced secretion persists following weight loss (WL), if other appetite-inhibiting hormones are also reduced, and if so whether reduced secretion results from intrinsic changes in the gut. To address whether WL may restore secretion of GLP-1 and other appetite-inhibiting hormones, we performed a gut perfusion study of the small intestine in diet-induced obese (DIO) rats after WL. A 20% weight loss (means ± SEM (g): 916 ± 53 vs. 703 ± 35, p < 0.01, n=7) was induced by calorie restriction, and maintained stable for ≥7 days prior to gut perfusion to allow for complete renewal of enteroendocrine cells. Age-matched DIO rats were used as comparator. Several gut hormones were analyzed from the venous effluent, and gene expression was performed on gut tissue along the entire length of the intestine. Secretion of cholecystokinin, gastrin, glucose-dependent insulinotropic peptide, GLP-1, neurotensin, and somatostatin was not affected by WL during basal conditions (p ≥ 0.25) or in response to macronutrients and bile acids (p ≥ 0.14). Glucose absorption was indistinguishable following WL. The expression of genes encoding the studied peptides, macronutrient transporters (glucose, fructose, and di-/tripeptides) and bile acid receptors did also not differ between DIO and WL groups. These data suggest that the attenuated postprandial responses of GLP-1, as well as reduced responses of other appetite-inhibiting gut hormones, in people living with obesity may persist after weight loss and may contribute to their susceptibility for weight regain.

Brush Border Membrane Vesicles from Rats and Gerbils Can Be Utilized to Evaluate the Intestinal Uptake of All-trans and 9-cis β-Carotene

Intestinal brush border membrane vesicles (BBMV) have previously been used to investigate the absorptive processes of a wide variety of nutrients. The first objective of this work was to develop a BBMV system to study carotenoid uptake using rat small intestine. The uptake of all-trans β-carotene by rat BBMV was linear up to 5.9 µmol/L, suggesting passive uptake at the concentrations used in this study. Both all-trans β-carotene and 9-cis β-carotene were taken up at a similar rate by the rat BBMV. The vesicle system was then utilized to investigate the uptake of retinol and β-carotene by BBMV isolated from Mongolian gerbils which had been subjected to three different vitamin A depletion and refeeding protocols. Three groups of gerbils (n = 10/group) were fed vitamin A-deficient diets for 8 wk. One group was killed at that point (marginally depleted), a second group was refed vitamin A for 5 d and a third group was further depleted of vitamin A for 5 d. Pooled BBMV from the marginally depleted group demonstrated greater uptake of all-trans β-carotene than pooled BBMV from the other two groups of gerbils while those from the group refed vitamin A for 5 d had greater uptake than the group that was depleted for 5 additional days (P < 0.01). In contrast, the uptake of retinol by BBMV was not significantly different among the three groups of gerbils. The results of the gerbil study suggest that as they become increasingly vitamin A deficient, impairment of all-trans β-carotene uptake by intestinal mucosal cells may be taking place. The BBMV system should prove valuable for the evaluation of the intestinal mucosal cell membrane uptake of carotenoids and retinoids under various nutritional conditions.

Digestion-Resistant Dextrin Derivatives Are Moderately Digested in the Small Intestine and Contribute More to Energy Production Than Predicted from Large-Bowel Fermentation in Rats

Background: Digestion-resistant dextrin derivatives (DRDDs), including resistant maltodextrin (RM), polydextrose, and resistant glucan (RG), have been developed as low-energy foods. However, data on the resistance of DRDDs to small-intestinal digestion are scarce.Objective: We sought to determine the site and extent of DRDD breakdown in the rat intestine and to predict its energy contributions.Methods: In vitro small-intestinal resistance of DRDDs was evaluated by the AOAC method for dietary fiber measurement and by artificial digestion with the use of pancreatic α-amylase and brush-boarder membrane vesicles. In vivo small-intestinal resistance of DRDDs was determined from the feces of male ileorectostomized Sprague-Dawley rats fed a control diet or a diet containing one of the DRDDs at 50 g/kg for 9 d (period 1) and then for 10 d (period 2), during which they received 1 g neomycin/L in their drinking water. Separately, male Sprague-Dawley rats were fed the same diets for 4 wk, and the whole-gut recoveries of DRDDs were determined from feces at days 8-10.Results: Small-intestinal resistances determined in vitro by artificial digestion (RM: 70%; polydextrose: 67%; RG: 69%) were lower than those measured by the AOAC method (RM: 92%; polydextrose: 80%; RG: 82%). In the ileorectostomized rats, fecal dry-matter excretions were consistently greater in the DRDDs than in the control. The small-intestinal resistances of the DRDDs were 68%, 58%, and 62% in period 1 and 66%, 61%, and 67% during period 2 for RM, polydextrose, and RG, respectively. The resistances did not differ among the DRDDs at either time. In the normal rats, food intakes and body weight gains did not differ among the groups. The whole-gut recovery of RM (13%) was lower than that of polydextrose (33%) and RG (29%), which did not differ.Conclusions: DRDDs were more digestible in the rat small intestine than the AOAC method. The energy contribution from small-intestine digestibility, not just large-bowel fermentability, must be considered in determining the energy contribution of DRDDs. Whether humans respond similarly needs to be tested.

Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause intestinal damage and ulcers and the incidence is increasing. Limonin plays an important role in the regulation of inflammatory diseases, but it has not been reported in the treatment of intestinal injury and ulcers. Indomethacin (INDO) induced intestinal injury and ulcer model in rats. The indexes related to intestinal injury were detected. Western blot and molecular docking techniques were used to detect the docking between Limonin and Nrf2. Next, ML385, an inhibitor of Nrf2/ARE signaling pathway, was applied to treat intestinal epithelial IEC-6 cells induced by INDO. And CCK8, Western blot, TUNEL, ELISA, DCFH-DA assay, kits, and immunofluorescence were conducted to detect cell activity, apoptosis, inflammatory response, oxidative stress, and tight junction again. INDO can significantly induce intestinal ulcerative lesions in rats. Limonin could improve intestinal ulcerative lesions induced by INDO in rats. Limonin could reduce INDO-induced inflammatory response and oxidative stress in the small intestine of rats, and improve the intestinal barrier dysfunction induced by INDO. Limonin could dock with Nrf2 structure and activate Nrf2/ARE signaling pathway. ML385 could reverse the protective effect of Limonin against INDO-induced cell damage. Limonin ameliorates INDO-induced intestinal damage and ulcers through Nrf2/ARE pathway.

Regional distributions of curcumin and tetrahydrocurcumin in the liver and small intestine of rats when orally co-administered with quercetin and paeoniflorin.

Curcumin (CUR), derived from the dietary spice turmeric, is a polyphenolic compound with various biological and pharmacological activities. Tetrahydrocurcumin (THC) is one of the major reductive metabolites of curcumin. A pharmacokinetic study using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of curcumin, THC, quercetin (QR), and paeoniflorin (PF) in rat plasma had been performed. In this study, the regional distributions of curcumin and tetrahydrocurcumin in the liver and the three segments of small intestine (duodenum, jejunum, and ileum) of rats when orally co-administered with quercetin and paeoniflorin were carried out. Drug concentrations were determined using UHPLC-MS/MS. The results showed that curcumin was well distributed in the small intestine, while the distributions of tetrahydrocurcumin in the liver, duodenum, jejunum were similar, but much more abundant in the ileum. When orally co-administered with quercetin and paeoniflorin, the tissue to plasma concentration ratios (Kp values) of curcumin in the three segments of the small intestine were increased, indicating that the presence of quercetin and paeoniflorin increases the distribution of curcumin in these regions. Moreover, the half-life (t1/2 ) of THC in the liver was significantly prolonged, and the Kp value of THC in the liver was increased and the Kp values in the small intestine were decreased, suggesting that the combination of quercetin and paeoniflorin might suppress the metabolism of curcumin in the small intestine. In brief, the combination had an effect on the distributions of curcumin and tetrahydrocurcumin in the liver and small intestine of rats.

The Impact of Long-Term Clinoptilolite Administration on the Concentration Profile of Metals in Rodent Organisms.

Heavy metals are dangerous systemic toxicants that can induce multiple organ damage, primarily by inducing oxidative stress and mitochondrial damage. Clinoptilolite is a highly porous natural mineral with a magnificent capacity to eliminate metals from living organisms, mainly by ion-exchange and adsorption, thus providing detoxifying, antioxidant and anti-inflammatory medicinal effects. The in vivo efficiency and safety of the oral administration of clinoptilolite in its activated forms, tribomechanically activated zeolite (TMAZ) and Panaceo-Micro-Activated (PMA) zeolite, as well as the impact on the metallic biodistribution, was examined in healthy female rats. Concentration profiles of Al, As, Cd, Co, Pb, Ni and Sr were measured in rat blood, serum, femur, liver, kidney, small and large intestine, and brain using inductively coupled plasma mass spectrometry (ICP-MS) after a 12-week administration period. Our results point to a beneficial effect of clinoptilolite materials on the concentration profile of metals in female rats supplemented with the corresponding natural clinoptilolite materials, TMAZ and PMA zeolite. The observed decrease of measured toxicants in the kidney, femur, and small and large intestine after three months of oral intake occurred concomitantly with their most likely transient release into the bloodstream (serum) indicative of a detoxification process.

Global cerebral ischemia followed by long-term reperfusion promotes neurodegeneration, oxidative stress, and inflammation in the small intestine in Wistar rats

AimsBrain ischemia and reperfusion may occur in several clinical conditions that have high rates of mortality and disability, compromising an individual’s quality of life. Brain injury can affect organs beyond the brain, such as the gastrointestinal tract. The present study investigated the effects of cerebral ischemia on the ileum and jejunum during a chronic reperfusion period by examining oxidative stress, inflammatory parameters, and the myenteric plexus in Wistar rats. Main methodsIschemia was induced by the four-vessel occlusion model for 15 min with 52 days of reperfusion. Oxidative stress and inflammatory markers were evaluated using biochemical techniques. Gastrointestinal transit time was evaluated, and immunofluorescence techniques were used to examine morpho-quantitative aspects of myenteric neurons. Key findingsBrain ischemia and reperfusion promoted inflammation, characterized by increases in myeloperoxidase and N-acetylglycosaminidase activity, oxidative stress, and lipid hydroperoxides, decreases in superoxide dismutase and catalase activity, a decrease in levels of reduced glutathione, neurodegeneration in the gut, and slow gastrointestinal transit. SignificanceChronic ischemia and reperfusion promoted a slow gastrointestinal transit time, oxidative stress, and inflammation and neurodegeneration in the small intestine in rats. These findings indicate that the use of antioxidant and antiinflammatory molecules even after a long period of reperfusion may be useful to alleviate the consequences of this pathology.

Chac1 silencing mitigates hemorrhagic shock-induced intestinal injury by inhibiting oxidative stress and ferroptosis

Hemorrhagic shock (HS) is a common and significant cause of mortality and morbidity, often resulting in structural damage and dysfunction of the intestines. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (Chac1) has been reported to be involved in the regulation of oxidative stress and ferroptosis in mammals. Herein, we investigate the effects of Chac1 on HS-induced intestinal injury induced by HS both in vitro and in vivo. Sprague-Dawley rat model with HS was established, and our investigations showed upregulation of the mRNA and protein levels of Chac1 in the model’s ileum tissues. Histopathological analysis revealed that knockdown of Chac1 attenuated the intestinal injury induced by HS. Depletion of Chac1 also reduced the increase in intestinal fatty acid binding protein (I-FABP) concentration. Immunofluorescence staining indicated that silencing Chac1 significantly suppressed the downregulation of occludin and zonula occludens-1 (ZO-1). HS-induced changes in lipid peroxidation (LPO), malondialdehyde (MDA), and glutathione (GSH) levels were reversed in the absence of Chac1, suggesting that downregulation of Chac1 alleviated HS-induced oxidative stress. Additionally, HS led to a decrease in glutathione peroxidase 4 (Gpx4) and ferritin heavy chain 1 (Fth1) expression, along with an increase in ferrous ion (Fe2+) concentration. Knockdown of Chac1 significantly inhibited ferroptosis by increasing Gpx4 and Fth1 expression while reducing the Fe2+ concentration. In vitro experiments using the rat small intestine crypt epithelial cells (IEC-6) demonstrated that depletion of Chac1 suppressed oxidative stress and ferroptosis induced by hypoxia/reoxygenation (H/R). In conclusion, our study provides evidence that downregulation of Chac1 mitigates HS-induced intestinal injury by inhibiting oxidative stress and ferroptosis.