Intestinal Myeloperoxidase Activity Research Articles

Codium fragile Suppresses PM2.5-Induced Cognitive Dysfunction by Regulating Gut-Brain Axis via TLR-4/MyD88 Pathway.

This study was conducted to evaluate the cognitive dysfunction improvement effect of aqueous extract of Codium fragile (AECF) by regulating the imbalance of the gut-brain axis in chronic particulate matter (PM)2.5-exposed mice. The physiological compounds of AECF were identified as hexadecanamide, oleamide, octadecanamide, stearidonic acid, and linolenic acid by the ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC Q-TOF MSE) analysis. To evaluate the effect of PM2.5 on the antioxidant system, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, and malondialdehyde (MDA) contents were measured in colon and brain tissues. AECF significantly ameliorated the imbalance of the antioxidant systems. Also, AECF improved intestinal myeloperoxidase (MPO) activity, the abundance of the gut microbiome, short-chain fatty acids (SCFAs) contents, and tight junction protein expression against PM2.5-induced damage. In addition, AECF prevented PM2.5-induced inflammatory and apoptotic expression via the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88) pathway in colon and brain tissues. Additionally, AECF enhanced the mitochondrial function, including the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) contents in brain tissues. Furthermore, AECF regulated the cholinergic system, such as acetylcholine (ACh) contents, acetylcholinesterase (AChE) activity, and protein expression levels of AChE and choline acetyltransferase (ChAT) in brain tissues. To evaluate the effect of cognitive dysfunction caused by PM2.5-induced intestinal dysfunction, behavior tests such as Y-maze, passive avoidance, and Morris water maze tests were performed. From the results of the behavior tests, AECF ameliorated spatial learning and memory, short-term memory, and long-term learning and memory function. This study confirmed that AECF reduced PM2.5-induced cognitive dysfunction by regulating gut microbiome and inflammation, apoptosis, and mitochondrial function by enhancing the gut-brain axis. Based on these results, this study suggests that AECF, which contains fatty acid amides, might be a potential material for ameliorating PM2.5-induced cognitive dysfunction via gut-brain axis improvement.

Targeting sting to reduce sepsis-induced acute intestinal injury

BackgroundSepsis is a dysregulated host response to infection syndrome leading to life-threatening organ dysfunction. Sepsis-induced intestinal dysfunction is a key element in the progression to multisystem organ failure. The stimulator of interferon genes is an intracellular protein implicated in intestinal injury in sepsis. H151, a small molecule inhibitor of stimulator of interferon genes, has not yet been studied as a potential therapeutic in sepsis. We hypothesize that H151 therapeutically reduces sepsis-induced acute intestinal injury. MethodsMale mice underwent cecal ligation and puncture and were treated with intraperitoneal H151 (10 mg/kg body weight) or vehicle. Intestines and serum were collected for analysis 20 hours after cecal ligation and puncture. Oral gavage of mice with FITC-dextran was performed 15 hours after cecal ligation and puncture. Five hours after gavage, serum was collected, and intestinal permeability was assessed. Mice were monitored for 10 days after cecal ligation and puncture to assess survival. ResultsZonula occludens 1 tight junctional protein expression was reduced after cecal ligation and puncture and recovered with H151 treatment. This was associated with a 62.3% reduction in intestinal permeability as assessed by fluorimetry. After cecal ligation and puncture, treatment with H151 was associated with a 58.7% reduction in intestinal histopathologic injury (P < .05) and a 56.6% reduction in intestinal apoptosis (P < .05). Intestinal myeloperoxidase activity was decreased by 70.8% after H151 treatment (P < .05). Finally, H151 improved 10-day survival from 33% to 80% after cecal ligation and puncture (P = .011). ConclusionH151, a novel stimulator of interferon genes inhibitor, reduces intestinal injury, inflammation, and permeability when administered as a treatment for cecal ligation and puncture-induced sepsis. Thus, targeting stimulator of interferon genes shows promise as a therapeutic strategy to ameliorate sepsis-induced acute intestinal injury.

Remote Ischaemic Pre-Conditioning Reduces Intestinal Ischaemia Reperfusion Injury in a Newborn Rat

ObjectiveRemote ischaemic conditioning (RIC) has been shown to reduce ischaemia-reperfusion injury(IRI) in multiple organ systems. IRI is seen in multiple bowel pathologies in the newborn, including NEC. We investigated the potential of RIC as a novel therapy for various intestinal pathologies in the newborn. MethodsWe used an established intestinal IRI model in rat pups which results in similar intestinal injury to necrotising enterocolitis (NEC). Animals were randomly allocated to IRI only(n = 14), IRI + RIC(n = 13) or sham laparotomy(n = 10). The macroscopic extent of intestinal injury is reported as a percentage of total small bowel. Injury severity was measured using Chiu-Park scoring. Neutrophil infiltration/activation was assayed by myeloperoxidase activity. Immunohistochemistry was used to assess the expression of hypoxia-inducible factor alpha (HIF-1α). Data are median (interquartile range). ResultsAnimals that underwent RIC showed a decreased extent of macroscopic injury from 100%(85–100%) in the IRI only group to 58%(15–84%, p = 0.003) in the IRI + RIC group. Microscopic injury score was significantly lower in animals that underwent RIC compared to IRI alone (3.5[1.25–5] vs 5.5[4–6], p = 0.014). Intestinal myeloperoxidase activity in animals exposed to IRI was 3.4 mU/mg of tissue (2.5–3.7) and 2.1 mU/mg(1.5–2.8) in the IRI + RIC group(p = 0.047). HIF-1α expression showed a non-significant trend towards reduced expression in the IRI + RIC group. ConclusionsRIC reduces the extent and severity of bowel injury in this animal model, supporting the hypothesis that RIC has therapeutic potential for intestinal diseases in the newborn.

Evaluation of a Functional Craft Wheat Beer Fermented with Saccharomyces cerevisiae UFMG A-905 to treat Salmonella Typhimurium infection in mice.

Functional foods containing probiotics are generally administered as dairy products. Non-dairy beverages are another possibility, but probiotic functionality must be confirmed in such vehicles. In the present study, a craft wheat beer brewed with the probiotic yeast Saccharomyces cerevisiae UFMG A-905 (905) was evaluated in a murine model of Salmonella Typhimurium infection. Unfiltered or filtered beer brewed with 905, a commercial wheat beer used as a negative control, or saline were administered orally to mice before and during oral S. Typhimurium challenge. High fecal levels of yeast were only counted in mice treated with the unfiltered 905 beer, which also had reduced mortality and body weight loss due to S. Typhimurium infection. Increased levels of intestinal IgA, translocation to liver and spleen, liver and intestinal lesions, pro-inflammatory cytokines in liver and ileum, and hepatic and intestinal myeloperoxidase and eosinophilic peroxidase activities were observed in animals infected with S. Typhimurium. All these parameters were reduced by the treatment with unfiltered 905 beer. In conclusion, the results show that a craft wheat beer brewed with S. cerevisiae UFMG A-905 maintained the probiotic properties of this yeast when administered orally to mice challenged with S. Typhimurium.

Inhibition of Bruton's Tyrosine Kinase Protects Against Burn Sepsis-Induced Intestinal Injury.

This study aimed to investigate the role and molecular mechanisms of Bruton's tyrosine kinase (BTK), a member of the Tec family in burn sepsis-induced intestinal injury. Eighty C57BL/6 mice were randomly divided into four groups: the sham group, the burn group, the burn + sepsis group, and the burn + sepsis + LFM-A13 (a selective BTK inhibitor) group. The dynamic expression profiles of BTK and p-BTK in the intestine were measured by Western blot analysis. Intestinal histopathological changes and cellular apoptosis were determined. Inflammatory cytokines in serum and intestinal tissue were examined through enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) activity was determined via a colorimetric assay. Intestinal p-BTK expression in the burn+sepsis group was significantly increased compared with that in the sham and burn groups. In the burn + sepsis group, the p-BTK expression level increased over time, peaked at 12, and then decreased at 24 h. LFM-A13 administration significantly inhibited p-BTK expression in the intestine. In contrast to the sham and burn groups, the burn + sepsis group exhibited obvious histopathological changes, which gradually aggravated over time. LFM-A13 also reduced the histopathological changes and cellular apoptosis in intestinal tissues, inhibited the inflammatory cytokines IL-4, IL-6, and TNF-α in serum and intestinal tissues, and significantly inhibited the increase in intestinal MPO activity induced by burn sepsis. BTK activation is one important aspect of the signaling event that may mediate the release of the anti-inflammatory cytokine IL-4 and the pro-inflammatory cytokines IL-6 and TNF-α; oxidative stress; and intestinal cell apoptosis. Thus, it contributes to burn sepsis-induced intestinal injury.

Effects of Cola anomala (K. Schum.) water/ethanol pods extract on the inflammation and intestinal secretion in lipopolysaccharide-induced diarrhea

Diarrhea is one of the leading causes of death among children in low and low-middle income countries and the management of this pathology is still a problem in these regions. The water/ethanol extract of the pods of Cola anomala (KEO) has been shown to possess antimicrobial and antidiarrheal effects in Shigella flexneri-induced diarrhea, but whether KEO is active on the toxemic part of this diarrhea is unknown. This study was undertaken to evaluate the effects of KEO on the intestinal secretion and inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS). KEO obtained by maceration in water/ethanol (1:1) was administered orally (25, 50 and 100 mg/kg of body weight) against LPS-induced diarrhea in mice. The mass of feces, the intestinal nitric oxide (NO) and prostaglandin (PGE2) contents as well as myeloperoxidase (MPO) activity were assessed. KEO was also tested on LPS-induced enteropooling in rats. In this experiment, the intestinal fluid and its electrolytes (Na+, K+ and Cl-) contents were determined as well as NO, PGE2, TNF-α and IL-1β levels in the small intestine homogenate. Indomethacin (5 mg/kg) was used as reference drug. KEO significantly (p &lt; 0.001) reduced stools excretion, NO content and MPO activity in intestine but did not affect PGE2 in LPS-induced diarrhea. On the enteropooling model, KEO showed no effect on the intestinal fluid and electrolyte excretion, PGE2, TNF-α and IL-1β contents, but significantly (p &lt; 0.05) reduced the NO production. This study suggests that KEO does not have antisecretory effect, but has anti inflammatory activities. It can be concluded that the anti-toxemic effect of KEO contributes less to its antidiarrheal activity in infectious diarrhea.

Dietary β-glucan (MacroGard®) improves innate immune responses and disease resistance in Nile tilapia regardless of the administration period

The effects of dietary β-glucan on innate immune responses have been shown in a number of different vertebrate species. However, there is conflicting information about the period of administration (shorter vs. longer), and it is also unclear to what extent β-glucan's effects can be observed post-treatment in fish. Thus, we fed Nile tilapia for 0 (control group; 45 days of control diet), 15 (30 days of control followed by 15 days of β-glucan), 30 (15 days of control followed by 30 days of β-glucan) or 45 days with a diet containing 0.1% of β-glucan (MacroGard®). We evaluated the growth performance at the end of the β-glucan feeding trial and the innate immune function immediately after the feeding trial and 7 and 14 days post-feeding trial. In addition, at day 10 post-feeding trial, we assessed the tilapia's resistance against a bacterial infection. No significant differences were observed in growth performance between the groups; however, fish fed with β-glucan for 30 and 45 days had higher (approx. 8%) relative weight gain compared to the control. Regardless of the administration period, fish fed with β-glucan had higher innate immune responses immediately after the feeding trial such as lysozyme activity in plasma, liver and intestine and respiratory burst compared to the control, and in general these differences were gradually reduced over the withdrawal period (up to 14 days). No differences were observed in the plasma hemolytic activity of the complement or myeloperoxidase activity in plasma or intestine. Moreover, fish from the control group had early mortalities (2 vs. 4–5 days post-infection, respectively) and a lower survival rate (60 vs. 80%, respectively) compared to fish fed with β-glucan for 15 or 30 days, and, interestingly, fish fed for 45 days with β-glucan had no mortality. This study indicates that regardless of the administration period (i.e., 15 up to 45 days), the β-glucan improved the innate immune responses and the tilapia's resistance to disease, and this protection could be observed up to 10 days post-feeding trial, adding in vivo evidence that β-glucan may contribute to a trained innate immunity. Additionally, we showed that a longer period of administration did not cause immunosuppression as previously hypothesized but promoted further growth and immune performance. These findings are relevant to the aquaculture industry and demonstrate that a longer β-glucan feeding protocol may be considered to achieve better results.

Somatostatin receptor subtype 4 protects against indomethacin-induced gastrointestinal mucosal injury in mouse

Abstract Despite recent advancements in the pharmacologic and endoscopic management of gastrointestinal ulceration, it is still associated with high mortality. Therefore, it is important to understand mucosal protective mechanisms. Somatostatin, present in the endocrine cells &amp; sensory nerves, and its analogues reduce mucosal blood flow, pepsin and gastric acid secretion. Its receptor subtype 4 (sst4) mediates anti-inflammatory &amp; analgesic actions, as discovered by our group. Therefore, our aim was to investigate its role in gastrointestinal injury. We treated sst4 gene-deleted (sst4−/−) and wildtype mice with indomethacine (IDM; 35 mg/kg) or vehicle s.c.. Gastric &amp; small intestine lesions were evaluated after 4 &amp; 48 h macroscopically &amp; microscopically. Plasma protein extravasation &amp; myeloperoxidase (MPO) activity were assessed by ex vivo imaging, TNFα, IL-1, COX2, sst4 &amp; somatostatin mRNA levels by qPCR. Gastric (4h) and small intestinal macroscopic (24 h) lesions, MPO activity (24, 48 h), and plasma extravasation (30 min) were significantly greater in IDM-treated sst4−/− mice, while histopathological scores &amp; small intestinal length did not show strain difference. TNFα, IL-1, COX2 significantly upregulated after 4h in the stomach of sst4−/− mice, and the same pattern was observable in wildtype mice at later timepoint (48 h). These results provide evidence for the protective role of the sst4 receptor against IDM-induced gastrointestinal mucosal injury. This suggests the safety of sst4 agonist drug candidates in the gastrointestinal tract, and even their potential use for gastroprotective indication. Supported by: GINOP-2.3.2-15-2016-00050 – PEPSYS, GINOP-2.3.2 STAY ALIVE, EFOP-3.6.2-16-2017-00008, ÚNKP-19-3-III-PTE-211

Effect of dietary supplementation with citral-loaded nanostructured systems on innate immune responses and gut microbiota of silver catfish (Rhamdia quelen)

Abstract Citral is a monoterpenoid found in the essential oils of several plant species, recognized as a safe diet additive and extensively used in the food and cosmetic industries. This study evaluated the effects of dietary supplementation with citral (0.25 g/kg), loaded in nanosystems or unloaded on the gastrointestinal tract (GIT) pH, hepatosomatic and intraperitoneal fat index, innate immune responses and gut microbiota (GM) of silver catfish (Rhamdia quelen). The treatments were: control diet (CO), diet containing unloaded citral (UC), diet containing citral-loaded nanoemulsions (NE), and diet containing citral-loaded alginate nanoparticles (NP). After 21 days fish fed all diets containing citral showed an increased liver lysozyme activity, whereas fish fed UC showed reduced serum hemolytic activity and intestinal myeloperoxidase activity. Serum lysozyme activity was lower in fish fed diet containing NP, whereas fish fed NE showed a reduced blood macrophage phagocytic index. Citral reduced stomach pH (all delivery forms) and increased intestinal pH when loaded in NE. Both NE and NP reduced the total bacterial population in the fish intestine, whereas Aeromonas spp. in intestine were higher in fish fed diet containing NP. Citral modulated the silver catfish immune responses, GIT pH and GM in a delivery mode-dependent manner.

Proteins from Plumeria pudica latex exhibit protective effect in acetic acid induced colitis in mice by inhibition of pro-inflammatory mechanisms and oxidative stress

Latex proteins from P. pudica (LPPp) have anti-inflammatory activity. In the present study, LPPp was evaluated to protect animals against inflammatory ulcerative colitis (UC). UC was induced by intracolonic instillation of a 6% acetic acid solution and the animals received LPPp (10, 20 or 40 mg/kg) by intraperitoneal route 1 h before and 17 h after acetic acid injection. Eighteen hours after instillation of acetic acid, the mice were euthanized and the colons were excised to determine the wet weight, macroscopic and microscopic lesion scores, myeloperoxidase (MPO) activity, IL1-β levels, glutathione (GSH) and malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. The results revealed that LPPp treatment (40 mg/kg) had a protective effect on acetic acid-induced colitis by reducing the wet weight, macroscopic and microscopic scores of intestinal lesions and colonic MPO activity. Additionally, LPPp inhibited tissue oxidative stress, since decreases in GSH consumption, MDA concentration and SOD activity were observed. The treatment with LPPp reduced the levels of cytokine IL-1β, contributing to the reduction of colon inflammation. Biochemical investigation showed that LPPp comprises a mixture of proteins containing proteinases, chitinases and proteinase inhibitors. These data suggest that LPPp has a protective effect against intestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration, cytokine release and oxidative stress.

Involvement of calcium-sensing receptor activation in the alleviation of intestinal inflammation in a piglet model by dietary aromatic amino acid supplementation.

Ca2+-sensing receptor (CaSR) represents a potential therapeutic target for inflammatory bowel diseases and strongly prefers aromatic amino acid ligands. We investigated the regulatory effects of dietary supplementation with aromatic amino acids - tryptophan, phenylalanine and tyrosine (TPT) - on the CaSR signalling pathway and intestinal inflammatory response. The in vivo study was conducted with weanling piglets using a 2×2 factorial arrangement in a randomised complete block design. Piglets were fed a basal diet or a basal diet supplemented with TPT and with or without inflammatory challenge. The in vitro study was performed in porcine intestinal epithelial cell line to investigate the effects of TPT on inflammatory response using NPS-2143 to inhibit CaSR. Dietary supplementation of TPT alleviated histopathological injury and decreased myeloperoxidase activity in intestine challenged with lipopolysaccharide. Dietary supplementation of TPT decreased serum concentration of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-12, granulocyte-macrophage colony-stimulating factor, TNF-α), as well as the mRNA abundances of pro-inflammatory cytokines in intestine but enhanced anti-inflammatory cytokines IL-4 and transforming growth factor-β mRNA levels compared with pigs fed control diet and infected by lipopolysaccharide. Supplementation of TPT increased CaSR and phospholipase Cβ2 protein levels, but decreased inhibitor of NF-κB kinase α/β and inhibitor of NF-κB (IκB) protein levels in the lipopolysaccharide-challenged piglets. When the CaSR signalling pathway was blocked by NPS-2143, supplementation of TPT decreased the CaSR protein level, but enhanced phosphorylated NF-κB and IκB levels in IPEC-J2 cells. To conclude, supplementation of aromatic amino acids alleviated intestinal inflammation as mediated through the CaSR signalling pathway.

Differential Effects of Brain Death on Rat Microcirculation and Intestinal Inflammation: Female Versus Male.

Brain death (BD) affects organs by multiple mechanisms related to hemodynamic effects, hormonal changes, and the systemic inflammatory response, which reduce organ function and viability. BD reduces microcirculatory perfusion in rat mesentery; this disturbance is also observed in the pancreas and lungs. Sex hormones can affect microcirculatory function, altering tissue perfusion and influencing the inflammatory process. Here, we present differences between sexes in the microcirculatory alterations generated by BD and in inflammatory infiltrate. Male, female, and ovariectomized-female Wistar rats were submitted to BD by intracranial balloon catheter sudden inflation. BD was confirmed by maximally dilated and fixed pupils, apnea, absence of reflexes, and a drop in mean arterial pressure. Perfusion and flow of the mesenteric microcirculation were analyzed. Intestinal myeloperoxidase activity and leukocyte infiltration were quantified. ELISA quantified serum estradiol, corticosterone, and inflammatory mediators, whereas expression of eNOS, endothelin, and endothelial adhesion molecule was measured by immunohistochemistry. Male rats presented lower percentages of mesenteric perfused microvessels and reduced blood flow compared to females. The female group presented higher eNOS and endothelin expression. Leukocyte infiltration into intestinal walls was higher in females in comparison to that in males. Moreover, the female group showed higher mesenteric vessel ICAM-1 expression than males, whereas serum TNF-α, IL-1β, and IL-10 levels did not differ between sexes. The high estradiol concentration before BD and high eNOS expression apparently favored the maintenance of microvascular perfusion/flow; however, BD caused an acute reduction of female sex hormone concentration and higher ICAM-1 level; thus, the proinflammatory organ status after BD is favored.

Influence of an ω3-fatty acid-enriched enteral diet with and without added glutamine on the metabolic response to injury in a rat model of prolonged acute catabolism.

In critically ill patients, acute injury alters gut function, causing greater risk for sepsis and malnutrition. Peptide-enriched diets may promote nitrogen absorption, whereas ω3-enriched diets reduce alterations in gut barrier function. The aim of this study was to assess the effectiveness of a peptide- and ω3-enriched diet on the metabolic response to injury and the gut barrier function in a model of prolonged catabolism in the rat. Given the intestinal trophic effect of glutamine, we tested for a synergistic effect of glutamine. We randomized 40 male Sprague-Dawley rats (250g) into four groups to enterally receive a standard high-protein diet (S), or a peptide- and ω3-enriched diet either alone (IMN) or supplemented with glutamine and alanine supplied as dipeptide (DIP) or as free amino acids (AAs) for 4d. Metabolic response to injury was induced by turpentine injections on days 1 and 3. At sacrifice, nutritional and inflammatory biomarkers and intestinal and liver function were assessed. Weight gain (+45-62%) and nitrogen balance (+33-56%) were significantly higher in all groups than in the S group. In jejunal mucosa, total glutathione was significantly higher (+20-30%) and myeloperoxidase activity significantly lower in all groups compared with the S group. Hepatictriacylglycerol content was significantly lower in the AA (0.30±0.04μM/g) and DIP (0.43±0.08μM/g) groups than in the S group (0.71±0.08μM/g). In this model of prolonged catabolism, compared with a standard diet, a peptide- and ω3-enriched diet improved metabolic response to injury, with better nitrogen balance and weight recovery, and decreased intestinal myeloperoxidase activity. Only marginal additional effects of glutamine supplementation were observed with decreased hepatic fat content.

Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses.

Bifidobacterium, a major component of the intestinal microbiota, has been clinically used for the treatment of diarrhoea and constipation. 5-Fluorouracil (5-FU), widely used for cancer chemotherapy, is known to frequently induce intestinal mucositis accompanied by severe diarrhoea. The present study examined the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on 5-FU-induced intestinal mucositis in mice. Intestinal mucositis was induced by repeated administration of 5-FU for 6days. BBG9-1 was administered orally once daily for 9days, beginning 3days before the onset of 5-FU treatment. Repeated administration of 5-FU caused severe intestinal mucositis, characterised by shortening of villi and destruction of crypts, accompanied by increases in intestinal myeloperoxidase activity and inflammatory cytokine expression, body weight loss, and diarrhoea on day 6. Daily administration of BBG9-1 significantly reduced the severity of intestinal mucositis and inflammatory responses and tended to attenuate clinical symptoms. In contrast, BBG9-1 failed to prevent apoptosis induction on day 1 after the first 5-FU administration. The structure of the intestinal microbiota, as analysed by weighted UniFrac distance, was largely altered by 5-FU treatment, but this change was mitigated by daily administration of BBG9-1. Moreover, 5-FU treatment decreased the abundance of Firmicutes and increased the abundance of Bacteroidetes, but these responses were also significantly inhibited by daily administration of BBG9-1. These results suggest that BBG9-1 has an ameliorative effect against 5-FU-induced intestinal mucositis through the attenuation of inflammatory responses via improve dysbiosis. BBG9-1 could be useful for the prevention of intestinal mucositis during cancer chemotherapy.

Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats.

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats.

A cafeteria diet triggers intestinal inflammation and oxidative stress in obese rats

The gastrointestinal alterations associated with the consumption of an obesogenic diet, such as inflammation, permeability impairment and oxidative stress, have been poorly explored in both diet-induced obesity (DIO) and genetic obesity. The aim of the present study was to examine the impact of an obesogenic diet on the gut health status of DIO rats in comparison with the Zucker (fa/fa) rat leptin receptor-deficient model of genetic obesity over time. For this purpose, female Wistar rats (n 48) were administered a standard or a cafeteria diet (CAF diet) for 12, 14·5 or 17 weeks and were compared with fa/fa Zucker rats fed a standard diet for 10 weeks. Morphometric variables, plasma biochemical parameters, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) levels in the ileum were assessed, as well as the expressions of proinflammatory genes (TNF-α and inducible nitric oxide synthase (iNOS)) and intestinal permeability genes (zonula occludens-1, claudin-1 and occludin). Both the nutritional model and the genetic obesity model showed increased body weight and metabolic alterations at the final time point. An increase in intestinal ROS production and MPO activity was observed in the gastrointestinal tracts of rats fed a CAF diet but not in the genetic obesity model. TNF-α was overexpressed in the ileum of both CAF diet and fa/fa groups, and ileal inflammation was associated with the degree of obesity and metabolic alterations. Interestingly, the 17-week CAF group and the fa/fa rats exhibited alterations in the expressions of permeability genes. Relevantly, in the hyperlipidic refined sugar diet model of obesity, the responses to chronic energy overload led to time-dependent increases in gut inflammation and oxidative stress.

Effects of heme oxygenase-1 recombinant Lactococcus lactis on the intestinal barrier of hemorrhagic shock rats.

This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280–320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.

Novel Gut Barrier Modulatory Effect of Vildagliptin in Amelioration of Bacterial Translocation in Cholestatic Rats

Intestinal barrier dysfunction is frequently implicated in the etiology of septic complications following obstructive jaundice. The present study was conducted to investigate the potential gut barrier modulating effect of vildagliptin (VLD), a dipeptidyl peptidase‐IV (DPP‐IV) inhibitor, on common bile duct ligation (CBDL) in rats. VLD (10 mg/kg/d; p.o) was administered for 10 successive days after CBDL in male Sprague‐Dawley rats. VLD reduced portal endotoxemia induced by CBDL and suppressed rectal temperature elevation, body weight loss and colon and spleen indices to different extends. Moreover, it reversed villous blunting, low villous density, mucosal thinning and inflammatory cell infiltration noticed microscopically in the ileal segments of the CBDL rats. These events were accompanied by the reduction of intestinal myeloperoxidase activity and lipid peroxidation, the elevation of the major anti‐oxidant molecule, glutathione, as well as the normalization of ileal nitric oxide level. Furthermore, ileal DPP‐IV was inhibited in association with the rise in ileal glucagon‐like peptide‐1 (GLP‐1) and insulin‐like growth factor‐1 (IGF‐1) levels in VLD treated animals. The current findings suggest that VLD anti‐oxidant, anti‐inflammatory, as well as enhancements of incretin and IGF‐1 account for the hardwearing of the intestinal barrier that functions competently in the absence of the supporting bile elements.

Antioxidant Effects of Probiotics in Experimentally Induced Peritonitis.

An experimental study was performed to evaluate the protective effects of probiotics on gut mucosa in peritonitis through antioxidant mechanisms. Thirty-two male Wistar albino rats were divided equally into four groups. The rats in Group 1 (control group) underwent laparotomy only. In group 2 (peritonitis group), peritonitis was induced in the rats by the cecal ligation and puncture (CLP) model. In group 3, the rats were treated with probiotics for five days after CLP-induced peritonitis. The last group of rats (group 4) were fed probiotics for five days before the CLP procedure and five days after the surgery. On the fifth day after surgery, all rats were killed, and tissue samples from the terminal ileum were obtained to evaluate the activities of myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH). Histopathologic examinations were also performed to evaluate the grade of intestinal injury. Myeloperoxidase and MDA activities were increased, GSH concentrations were decreased in group 2, compared with group 1. Intestinal MPO activities in group 4 were decreased compared with group 1 and group 2, indicating a reduction in oxidant activity. Malondialdehyde decreased in group 3 and decreased even more in group 4, compared with the peritonitis group (group 2). Glutathione concentrations were increased in group 4 compared with group 2 and group 3 (p < 0.05). The Chiu scores of the probiotics groups, groups 3 and 4, were lower than those in group 2, indicating reduced mucosal damage in the probiotically fed groups. Probiotics have protective effects in peritonitis, which may be related to antioxidant mechanisms. This antioxidant effect of probiotics might occur when pre-conditioning with probiotics before peritonitis because there is sufficient time to prepare the tissues for oxidative damage.

Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.