Procyanidin A_1 and its digestive products alleviate acrylamide-induced IPEC-J2 cell damage through regulating Keap1/Nrf2 pathway

Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In this study,we elucidated the molecular mechanism for and D-A_(1) to alleviate ACR-stimulated IPEC-J2 cell damage.ACR slightly activated nuclear factor erythroid 2-related factor 2(Nrf2)signaling and its target genes,but this activation could not reduce intestine cell damage.A_(1) and D-A_(1) could alleviate ACR-induced cell damage,but the effect was abrogated in cells transiently transfected with Nrf2 small interfering RNA(siRNA).Further investigation confirmed that A_(1) and D-A_(1) interacted with Ketch-like ECH-associated protein 1(Keapl),which boosted the stabilization of Nrf2,subsequently promoted the translocation of Nrf2 into the nucleus,and further increased the expression of antioxidant proteins,thereby inhibiting glutathione(GSH)consumption,maintaining redox balance and eventually alleviating ACR-induced cell damage.Importantly,there was no difference between A_(1) and D-A_(1) treated groups,indicating that A_(1) can tolerate gastrointestinal digestion and may be a potential compound to limit the toxicity of ACR.

Effect of Jiaotai Pill(交泰丸)on Intestinal Damage in Partially Sleep Deprived Rats

Objective: To explore the effect and mechanism of Jiaotai Pill(交泰丸, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation(PSD). Methods: Obesity resistant(OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide(LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin(Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes(Cry1 and Cry2) in the intestine were also determined. Results: The treatment of JTW significantly decreased LPS level in OR rats with PSD(P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting(P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. Conclusions: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.

Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets

Intestinal oxidative stress triggers gut microbiota dysbiosis,which is involved in the etiology of postweaning diarrhea and enteric infections.Ellagic acid(EA)can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis.Therefore,we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage,oxidative stress,and dysbiosis of gut microbiota in weanling piglets.A total of126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 m L saline orally(Ctrl group),or the basal diet supplemented with 0.1%EA and 2 m L saline orally(EA group),or the basal diet and 2 m L fecal microbiota suspension from the EA group orally(FEA group),respectively,for 14 d.Compared with the Ctrl group,EA group improved growth performance by increasing average daily feed intake and average daily weight gain(P<0.05)and decreasing fecal scores(P<0.05).EA group also alleviated intestinal damage by increasing the tight junction protein occludin(P<0.05),villus height,and villus height-to-crypt depth ratio(P<0.05),while decreasing intestinal epithelial apoptosis(P<0.05).Additionally,EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity(P<0.01),catalase(P<0.05),and glutathione/oxidized glutathione(P<0.05),but decreased the oxidative metabolite malondialdehyde(P<0.05)compared to the Ctrl group.Compared with the Ctrl group,EA and FEA groups increased alpha diversity(P<0.05),enriched beneficial bacteria(Ruminococcaceae and Clostridium ramosum),and increased metabolites short-chain fatty acids(P<0.05).Correspondingly,FEA group gained effects comparable to those of EA group on growth performance,intestinal damage,and intestinal antioxidant capacity.In addition,the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices(P<0.05).Overall,dietary EA supplementation could improve growth performance and attenuate intestinal damage and oxidative stress by regulating the gut microbiota in weanling piglets.

Non-invasive markers of gut wall integrity in health and disease

The intestinal mucosa is responsible for the absorption of nutrients from the lumen and for the separation of the potentially toxic luminal content(external environment) from the host(internal environment).Disruption of this delicate balance at the mucosal interface is the basis for numerous(intestinal) diseases.Experimental animal studies have shown that gut wall integrity loss is involved in the development of various inflammatory syndromes,including post-operative or post-traumatic systemic inflammatory response syndrome,sepsis,and multiple organ failure.Assessment of gut wall integrity in clinical practice is still a challenge,as it is difficult to evaluate the condition of the gut non-invasively with currently available diagnostic tools.Moreover,non-invasive,rapid diagnostic means to assess intestinal condition are needed to evaluate the effects of treatment of intestinal disorders.This review provides a survey of non-invasive tests and newly identified markers that can be used to assess gut wall integrity.

Histological and Morphological Study of the Intestines of Wistar Rat Fetuses in a Modified Gastroschisis Experimental Model

In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and histological alterations. The outcome of these alterations is intestinal hypoperistalsis and nutrient absorption deficiency, which contribute to increased morbidity and high medical-hospital costs. In this study, morphological and histological intestine alterations were identified at two different contact occasions with AF. Experimental gastroschisis (G) was performed on Wistar rat fetuses at a single gestational age on day 18.5th. The fetuses were removed on the 20.5th (G-1) and 21.5th days (G-2). Fetuses of both groups were divided in 3 sub-groups: control (C), gastroschisis (G) and sham (S). Measurements were taken of the Whole Set including fetus, placenta and membranes with AF (WS), fetus body weight (BW), intestinal weight (IW) and their diameters (DI). The objective of the present study is to test a new gastroschisis experimental model and identify differences in morphological and histological alterations in these two gestational periods that may be directly related to intestinal motility disorders in G. The WS and BW presented no significant statistical difference when compared G1 and G2. The results of the intestine average weight of G2 fetuses were significantly higher when compared to G1 fetuses in all subgroups (C: p = 0.02;G: p = 0.01;S: p = 0.02, Mann Whitney). The results of the intestinal average diameters (D/d) in G1 and G2 presented significant statistical difference only in G subgroup (p Kruskal Wallis). When compared intestinal average diameters, there was significant statistical difference of G fetuses in G1 and G2 (p Mann Whitney). In conclusion, the present experimental G model was adequate to reproduce G in rat fetuses. All G fetuses presented significant statistical difference when compared to other group in their subgroup and when compared G1 and G2 (p < 0.05). These alterations can explain the difficulties in accomplishing adequate peristalsis in G neonate bearers.

Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs

Background One of the major causes of death in severe acute pancreatitis （SAP） is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition （EIN） as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs. Methods SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition （PN） or elemental enteral nutrition （EEN） or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes （MLN）, liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum. Results Compared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury （ileum mocosa thickness, villus height, and crypt depth） were significantly alleviated by EIN （P〈0.05）. Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group. Conclusion Our results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in SAP dogs. Early EIN was safe and more effective treatment for SAP dogs.

姜黄根提取物对甲氨蝶吟诱导的肠损伤及氧化应激的保护作用(英文)

AIM:The most important side effect of methotrexate(MTX)is mucositis.The purpose of this study was to evaluate the effect of turmeric extract on intestinal damage and oxidative stress in rats receiving methotrexate.METHODS:Experiments were performed on male Wistar albino rats divided into six groups.First group received normal saline orally,the second group received turmeric extract(100 mg·kg-1)orally for 30 days,the third group received turmeric extract(200 mg·kg)orally for 30 days,the fourth group received a single dose of methotrexate(20 mg·kg)i.p.at day 30,the fifth group received turmeric extract(100 mg·kg)orally for 30 days and a single dose of methotrexate(20 mg·kg)i.p.at day 30,and the sixth group received turmeric extract(200 mg·kg)orally for 30days and single dose of methotrexate(20 mg·kg)i.p.at day 30.Four days after methotrexate injection,animals were anesthetized,blood samples were taken to determine total antioxidant status(TAS)and jejunum samples were taken for glutathione peroxidase(GPx),superoxidase dismutase(SOD),catalase(CAT),aldehyde malondialdehyde(MDA),and histopathological assessment.RESULTS: Microscopic evaluation from intestinal tissues of the MTX treated group,showed severe villus shortening and blunting,inflammatory cell infiltration and hemorrhage in lamina propria,along with epithlial cell necrosis.Levels of SOD,GSH-Px and CAT decreased in the MTX received group,but increased significantly(P<0.05)in the turmeric+MTX groups.MTX increased lipid peroxidation,however,turmeric decreased peroxidation significantly(P<0.05).CONCLUSION:These results suggest that turmeric extract may protect the small intestine of rats from methotrexate-induced damage.Turmeric effects could result from its antioxidant properties.