SEARCH · Search PubMed

Results for “Intestinal barrier”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources

PubMed2003

A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples.

Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time-consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS), is introduced. This novel approach requires an off-line ZipTip desalting step followed by automated nanoESI-MS/MS, using the NanoMate 100 and ESI Chip. In addition to reduced method development time, automated nanoESI-MS/MS also offers no carry-over between samples, low sample consumption, and ease-of-use as compared with conventional pulled-capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high-throughput. A comparison of Caco-2 samples analyzed both by LC/MS/MS and by automated nanoESI-MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI-MS/MS were in excellent agreement.

Algorithms↗

PubMed2026

A Review on Heat Stress in Broiler Chickens: Mechanisms, Effects and Mitigation Strategies.

BACKGROUND: Heat stress (HS) is a major environmental challenge for broilers, particularly under rising global temperatures and high humidity. Broiler chickens are highly susceptible because of their rapid growth rate, high metabolic heat production, limited thermoregulatory capacity and genetic selection for fast growth. OBJECTIVE: This review aims to synthesise current evidence, evaluate the effectiveness of existing mitigation strategies, identify key knowledge gaps and provide future research directions to improve broiler resilience, welfare and productivity under increasingly HS conditions. METHODS: This review synthesised evidence published between 2010 and 2025 on the physiological, metabolic, intestinal, immunological and productive consequences of HS and evaluated mitigation strategies. RESULTS: The reviewed studies demonstrate that HS reduces feed intake by approximately 10%-30%, suppresses body weight gain and feed efficiency and increases mortality, with severity depending on temperature, humidity and broiler genotype. HS disrupts carbohydrate, protein and lipid metabolism; induces acid-base imbalance and oxidative stress; compromises intestinal barrier integrity; alters gut microbiota; suppresses immune function; and reduces meat quality. Nutritional interventions, including dietary electrolyte balance, antioxidants, vitamins, selenium, zinc, phytogenic compounds, probiotics, betaine and optimised feeding strategies, environmental management and genetic approaches, including naked-neck and frizzle genes, can partially alleviate these adverse effects. However, inconsistencies among studies persist because of differences in broiler strains, environmental conditions, dietary formulations and experimental protocols. CONCLUSION: HS substantially compromises broiler health, welfare, productivity and meat quality. Nutritional, environmental and genetic approaches can partially mitigate its adverse effects; however, further research is needed to improve broiler resilience under increasingly HS conditions.

Animals↗

PubMed1998

Toxoplasma gondii: kinetics of the dissemination in the host tissues during the acute phase of infection of mice and rats.

Mice and rats differ in their susceptibility to Toxoplasma gondii infection. Here we have compared the parasitological parameters of acute infection in both mice and rats infected either orally with cysts of Prugniaud strain or intraperitoneally (ip) with tachyzoites of the RH strain. The animals were killed at regular interval during the acute phase, and the parasitic burden in mesenteric lymph nodes, spleen, liver, diaphragm, heart, lungs, brain, and blood was assessed by a tissue culture method in MRC5 fibroblast cells. Mice infected with the RH strain showed a drastic increase of the parasitic load in all organs (up to 10 (8) parasites / g of organs), and then died. When mice were infected with 50 cysts of Prugniaud strain, parasites were first observed in mesenteric lymph nodes, spleen, and lungs and then in other organs. In rats, infection with 1200 cysts of the same strain led to a similar pattern; however, the chronology of the infected organs changed when they were infected with RH strain tachyzoites. These results suggest that the parasites, present first in the peritoneal cavity in the case of RH ip infection, infect all the adjacent organs and then the blood which disseminates the tachyzoites all over the organism. In contrast, after an oral infection, the parasite crosses the intestinal barrier to reach the mesenteric lymph nodes and then the spleen and are finally distributed by the blood throughout the organism. We also showed that following infection with a lethal or a sublethal doses of the Prugniaud strain, the parasitic burden in the studied organs was similar and therefore does not directly correlate with the death of the mice.

Acute Disease↗

PubMed1994

Comparison of the acute biological action of injectable salmon calcitonin and an injectable and oral calcitonin analogue.

In most countries, calcitonin is available in the form of injections, and less frequently as an intranasal spray. An oral route of administration should improve compliance. In a preliminary feasibility study, we have compared the acute biological action of injectable salmon calcitonin (50 IU), with the injectable calcitonin analogue ASC 710 (0.2 mg) and oral ASC 710 (20 mg) in 6 patients suffering from active Paget's disease of bone. The intensity and duration of the biological response were not significantly different in the 3 modes of therapy. In conclusion, the oral calcitonin analogue ASC 710 possesses an antiresorbing activity in Paget's disease comparable to that of an injection of salmon calcitonin which demonstrates that it can cross the intestinal barrier.

Administration, Intranasal↗

PubMed1979

The fate of adenosine monophosphate in the rat after a single oral administration. Influence of a simultaneous treatment by papaverine.

The fate in the organism of Adenosine Monophosphate after a single oral administration of 10 mg/kg, was studied in the Rat, using 14C-labelled AMP. This paper deals more specially with the study of the plasmatic kinetics of AMP, since we proved at first that the AMP molecule goes intact through the intestinal barrier into the blood. The effects on these kinetics of a joint administration of Papaverine are considered.

Adenosine Monophosphate↗

PubMed2002

Differential induction of CYP1A1 in duodenum, liver and kidney of rats after oral intake of soil containing polycyclic aromatic hydrocarbons.

We have analyzed the induction of the cytochrome P450 enzyme CYP1A1 as a biomarker of effect in duodenum, liver and kidney of rats after oral intake of contaminated soil particles. The soil samples originated from industrial sites and were contaminated with polycyclic aromatic hydrocarbons (PAH) to variable extents, ranging from 60 to 4700 mg PAH/kg soil. Soil samples were administered for one week as a mixture with commercial rodent diets. After exposure, microsomes of several organs were prepared and analyzed for CYP1A1, enzymatically and by Western blots. All contaminated soils led to induction of CYP1A1 in duodenal mucosa cells, regardless of their extent of contamination, showing that relevant doses were mobilized in the gastrointestinal tract and adsorbed. Subsequent distribution of non-metabolized compounds is indicated by induction of CYP1A1 in the liver. However, some samples did not lead to a response in the liver, due to their quantitative and qualitative contaminant composition. In accordance with previous results, there is a sigmoidal dose-response relationship between induction of hepatic CYP1A1 levels and the soil contamination with higher condensates of PAH. In contrast, the response in the duodenum appeared to be hyperbolic and correlated well with the amounts of total PAH. Highly contaminated soil, being nearly devoid of higher condensates of PAH, led to pronounced induction in the duodenum but failed to induce CYP1A1 in the liver. Successful passage of contaminants through the intestinal barrier and the liver compartment is shown by increased CYP1A1 expression in the kidney. Compared with enzyme levels induced in the liver, those of the kidney are much lower and amount to only about 1/20 of the liver values for soils with high induction potential. Hence, oral PAH intake leads to differential induction patterns of CYP1A1 in duodenum, liver and kidney of rats. The observations raise questions concerning the role of the primary duodenal PAH metabolism in preventing contaminant-dependent hazardous effects, and of the significance of differential CYP1A1 expressions for carcinogenic processes in several tissues.

Animals↗

PubMed2000

Endotoxaemia does not limit heat tolerance in rats: the role of plasma lipoproteins.

Severe hyperthermia disrupts the intestinal barrier, allowing bacterial lipopolysaccharides (LPS) to enter the bloodstream. Since the symptoms of heat stroke resemble those of endotoxic shock, there is a common belief that endotoxaemia induces heat stroke. Therefore, we studied the effects of different doses, from moderate to sublethal, of Escherichia coli LPS and an antipyretic (indomethacin) upon the temperature equilibrium of the brain and body of rats exposed to a constant ambient temperature of 38 degrees C. The animals were then heated until they developed heat stroke, which was identified using a critical thermal maximum (CTM) behavioural test. In separate experiments on defence against endotoxaemia, we compared plasma lipid composition in rats exposed to a sublethal dose of LPS, hyperthermia and heat stroke. Neither LPS nor indomethacin, injected into rats while they were in a hyperthermic steady-state condition of 40-41 degrees C, influenced their thermal equilibrium. Unexpectedly, moderate doses of LPS significantly elevated the thermal tolerance of rats, such that the mean (SEM) CTM value of body temperature was raised from 42.7 (0.3) degrees C to 43.1 (0.1) degrees C (P < 0.05). Indomethacin and huge doses of LPS failed to induce any change in this parameter. The sublethal dose of LPS did not induce mortality in rats subjected to heat stroke. Hyperthermic steady-state conditions and heat stroke alone significantly decreased plasma concentrations of cholesterol, triglyceride and high-density lipoproteins, while the concentrations of low-density lipoproteins increased. A similar pattern of changes was recorded in normothermic rats injected with a sublethal dose of LPS. In conclusion, endotoxaemia in heat-stressed rats induces neither a secondary increase in their core temperature nor a decrease in their ultimate thermal tolerance. Low-density lipoproteins are likely to protect heat-stressed animals against endotoxin-induced death.

Animals↗

PubMed2026

Parasites and allergies: a complex bidirectional relationship from evolutionary origins to modern therapeutics.

Parasites and allergic diseases are linked by a complex, bidirectional relationship shaped by long-term host-parasite coevolution. This review discusses how different parasites may either promote or attenuate allergic responses through immunological, epithelial, and microbiome-mediated mechanisms. IgE-mediated immunity, mast cell activation, eosinophilia, and pruritus may have evolved as protective responses against helminths and blood-feeding ectoparasites. In contrast, modern allergies may partly reflect misdirected responses to harmless environmental antigens. The effects of parasites on allergy are not uniform and depend on parasite type, infection site, exposure intensity and chronicity, host immune status, and the degree of host-parasite adaptation. Protozoa such as Giardia intestinalis may contribute to food allergy-related manifestations by disrupting the intestinal barrier, altering gut microbiota composition, and modifying mucosal immune responses, particularly in atopic individuals. In contrast, selected helminths may attenuate allergic inflammation by inducing regulatory T and B cells, anti-inflammatory cytokines, antigen-presenting cell modulation, and IgG4-associated mechanisms that can limit IgE-mediated effector responses. Molecular similarities between parasite-derived antigens and environmental allergens, including conserved protein families and carbohydrate epitopes, may contribute to cross-reactive IgE responses and complicate allergy diagnostics. Therefore, current research is shifting from live helminth therapy toward defined parasite-derived molecules and immunomodulatory pathways that may inspire safer and more controlled therapeutic strategies. A clearer understanding of parasite-allergy interactions may improve diagnostic interpretation and support the development of new approaches to the management of allergic disease.

Humans↗

PubMed2005

CARD15/NOD2 is not a predisposing factor for necrotizing enterocolitis.

Multiple factors are incriminated in the etiopathogeny of necrotizing enterocolitis (NEC) in premature infants, including oral feeding, vascular abnormalities, increase in pro-inflammatory cytokines, and inappropriate response of the intestinal barrier to bacterial microflora. CARD15/NOD2 is a gene recently recognized as important in the innate response to gut flora and is involved in Crohn's disease susceptibility. We thus tested its putative role in NEC. Ten children (seven boys and three girls) suffering from NEC who were admitted to Robert Debré hospital between 1999 and 2002 were retrospectively included in the study. Genetic screening of the 11 constant exons and the exon-intron junctions of CARD15/NOD2 by direct sequencing revealed no novel mutations of that gene in NEC patients. Furthermore, the three main mutations of CARD15/NOD2 (R702W, G908R, and 1007fs) associated with susceptibility to Crohn's disease were not found in these patients. Our results suggest that CARD15/NOD2 does not play a major role in genetic susceptibility to NEC.

Crohn Disease↗

PubMed1983

Transmission of immunoglobulin to foetal and neonatal mice.

Transmission of immunoglobulin (Ig) classes and subclasses from mother to foetus and to neonate, and the survival of maternal Ig in the circulation of the young mouse up to 40 days after birth, has been quantitated in Balb/c homozygous and (Balb/c X SJL/J)F1 matings using isotype-specific heteroantisera in radial immunodiffusion in gel assays. The transfer of anti-allotype (anti-Ig-1b (gamma 2a] antibodies from immunised Balb/c mothers (Ig-1a) to F1 heterozygote (Ig-1ab) offspring was measured by passive haemagglutination of Ig-1b target allotype-coated sheep red blood cells. A small but significant level of transmission of Ig to the foetus occurs by the 15th day of gestation (5 days before birth) but the bulk of passively acquired Ig is derived from the milk after birth. All Ig acquired in utero and later across the intestinal barrier is exclusively of IgG isotypes (gamma 1, gamma 2a, gamma 2b) even though the milk has a large predominance of IgA. An appreciable level of maternally derived antibody is maintained in the circulation of the young mouse 24 days or more after gut 'closure' on the 16th day post-partum.

Amniotic Fluid↗

PubMed2004

Clinical endocrinology and metabolism. Glucagon-like peptide-1 and glucagon-like peptide-2.

The glucagon-like peptides (glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)) are released from enteroendocrine cells in response to nutrient ingestion. GLP-1 enhances glucose-stimulated insulin secretion and inhibits glucagon secretion, gastric emptying and feeding. GLP-1 also has proliferative, neogenic and antiapoptotic effects on pancreatic beta-cells. More recent studies illustrate a potential protective role for GLP-1 in the cardiovascular and central nervous systems. GLP-2 is an intestinal trophic peptide that stimulates cell proliferation and inhibits apoptosis in the intestinal crypt compartment. GLP-2 also regulates intestinal glucose transport, food intake and gastric acid secretion and emptying, and improves intestinal barrier function. Thus, GLP-1 and GLP-2 exhibit a diverse array of metabolic, proliferative and cytoprotective actions with important clinical implications for the treatment of diabetes and gastrointestinal disease, respectively. This review will highlight our current understanding of the biology of GLP-1 and GLP-2, with an emphasis on both well-characterized and more novel therapeutic applications of these peptides.

Animals↗

PubMed2004

Exploitation of host cell cytoskeleton and signalling during Listeria monocytogenes entry into mammalian cells.

Deciphering how Listeria monocytogenes exploits the host cell machinery to invade mammalian cells during infection is a key issue for the understanding how this food-borne pathogen causes a pleiotropic disease ranging from gastro-enteritis to meningitis and abortions. Using multidisciplinary approaches, essentially combining bacterial genetics and cell biology, we have identified two bacterial proteins critical for entry into target cells, InlA and InlB. Their cellular ligands have been also identified: InlA interacts with the adhesion molecule E-cadherin, while InlB interacts with the receptor for the globular head of the complement factor C1q (gC1q-R), with the hepatocyte growth factor receptor (c-Met) and with glycosaminoglycans (including heparan sulphate). The dynamic interaction between these cellular receptors and the actin cytoskeleton is currently under investigation. Several intracellular molecules have been recognized as key effectors for Listeria entry into target cells, including catenins (implicated in the connection of E-cadherin to actin) and the actin depolymerising factor/cofilin (involved in the rearrangement of the cytoskeleton in the InlB-dependent internalisation pathway). At the organism level, species specificity has been discovered concerning the interaction between InlA and E-cadherin, leading to the generation of transgenic mice expressing the human E-cadherin, in which the critical role of InlA in the crossing of the intestinal barrier has been clearly determined. Listeria appears as an instrumental model for addressing critical questions concerning both the complex process of bacterial pathogenesis and also fundamental molecular processes, such as phagocytosis.

Actins↗

PubMed2004

Exploitation of host cell cytoskeleton and signalling during Listeria monocytogenes entry into mammalian cells.

Deciphering how Listeria monocytogenes exploits the host cell machinery to invade mammalian cells during infection isa key issue for the understanding how this food-borne pathogen causes a pleiotropic disease ranging from gastro-enteritis to meningitis and abortions. Using multidisciplinary approaches, essentially combining bacterial genetics and cell biology, we have identified two bacterial proteins critical for entry into target cells, InlA and InlB. Their cellular ligands have been also identified: InlA interacts with the adhesion molecule E-cadherin, while InlB interacts with the receptor for the globular head of the complement factor Clq (gClq-R), with the hepatocyte growth factor receptor (c-Met) and with glycosaminoglycans(including heparan sulphate). The dynamic interaction between these cellular receptors and the actin cytoskeleton is currently under investigation. Several intracellular molecules have been recognized as key effectors for Listeria entry into target cells,including catenins (implicated in the connection of E-cadherin to actin) and the actin depolymerising factor/cofilin (involved in the rearrangement of the cytoskeleton in the InlB-dependent internalisation pathway). At the organism level, species specificity has been discovered concerning the interaction between InlA and E-cadherin, leading to the generation of transgenic mice expressing the human E-cadherin, in which the critical role of InlA in the crossing of the intestinal barrier has been clearly determined. Listeria appears as an instrumental model for addressing critical questions concerning both the complex process of bacterial pathogenesis and also fundamental molecular processes, such as phagocytosis.

Animals↗

PubMed2006

Procyanidins protect Caco-2 cells from bile acid- and oxidant-induced damage.

Procyanidins can exert cytoprotective, anti-inflammatory, and anticarcinogenic actions in the gastrointestinal tract. Previous evidence has shown that procyanidins can interact with synthetic membranes and protect them from oxidation and disruption. Thus, in this study we investigated the capacity of a hexameric procyanidin fraction (Hex) isolated from cocoa to protect Caco-2 cells from deoxycholic (DOC)-induced cytotoxicity, cell oxidant increase, and loss of monolayer integrity. Hex interacted with the cell membranes without affecting their integrity, as evidenced by a Hex-mediated increase in the transepithelial electrical resistance, and inhibition of DOC-induced cytotoxicity. DOC induced an increase in cell oxidants, alterations in the paracellular transport, and redistribution of the protein ZO-1 from cell-cell contacts into the cytoplasm. Hex partially inhibited all these events at concentrations ranging from 2.5 to 20 microM. Similarly, Hex (5-10 microM) inhibited the increase in cell oxidants, and the loss of integrity of polarized Caco-2 cell monolayers induced by a lipophilic oxidant (2,2'-azobis (2,4-dimethylvaleronitrile). Results show that the assayed procyanidin fraction can interact with cell membranes and protect Caco-2 cells from DOC-induced cytotoxicity, oxidant generation, and loss of monolayer integrity. At the gastrointestinal tract, large procyanidins may exert beneficial effects in pathologies such us inflammatory diseases, alterations in intestinal barrier permeability, and cancer.

Azo Compounds↗

PubMed2026

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin↗

PubMed2005

Comparison of monomeric and oligomeric transferrin as potential carrier in oral delivery of protein drugs.

Oligomeric transferrin (Tf) was used to investigate the effect that cross-linking of transferrin receptors (TfR) has on intracellular trafficking of the Tf-TfR complex and to determine whether or not the Tf-oligomer would be a better carrier than monomeric Tf for the oral delivery of protein drugs. The intracellular retention and transcytosis of the Tf-oligomer was determined by performing pulse chase studies on enterocyte-like Caco-2 cells. The intracellular retention of the Tf-oligomer was 2-fold higher than that of monomeric Tf while there was no significant difference in transcytosis. However, in vivo studies in CF-1 mice showed that the plasma concentrations of Tf from the orally administered Tf-oligomer were approximately 2-, 3- and 60-fold higher than that of orally administered monomeric Tf at 24, 48 and 72 h post-administration, respectively. In addition, the retention of the Tf-oligomer in the intestine was higher than that of monomeric Tf, which was consistent with in vitro studies. Insulin (In), when conjugated to the Tf-oligomer (Agg-Tf-S-S-In), was more effective than monomeric Tf-In conjugate (Mono-Tf-S-S-In) in reducing blood glucose levels when orally administered to streptozotocin (STZ)-induced diabetic rats. Post-oral administration of Agg-Tf-In, a delayed onset and prolonged hypoglycemic effect was observed. These results demonstrate that the cross-linking of TfR induced by the binding of the oligomeric Tf alters the intracellular trafficking and increases the intracellular retention of Tf-TfR complexes in polarized Caco-2 cells. The alteration of TfR trafficking could conceivably have caused the increase of insulin transport across the intestinal barrier when Agg-Tf-S-S-In was administered orally to STZ-induced diabetic rats. The delayed onset and prolonged effect of Agg-Tf-S-S-In in hypoglycemia strongly suggests that the Tf-oligomer can act as a sustained release carrier in the oral delivery of protein and peptide drugs.

Administration, Oral↗

PubMed2026

Potential contribution of the microbiota-gut-brain axis to doxorubicin-associated cognitive impairment: Mechanisms, evidence, and therapeutic opportunities.

Chemotherapy-induced cognitive impairment (CICI), often termed chemobrain, is a clinically important complication of cancer treatment that can affect memory, attention, executive function, and processing speed during and after therapy. Doxorubicin is of particular mechanistic interest because brain parenchymal exposure is limited, yet preclinical studies consistently identify neuroinflammatory, oxidative, vascular, and synaptic abnormalities after treatment. This critical narrative review evaluates whether intestinal injury and disruption of the microbiota-gut-brain axis may contribute to these central effects. Preclinical evidence indicates that doxorubicin can alter microbial community structure, injure the intestinal barrier, modify SCFA-associated taxa or predicted functions, alter selected metabolite profiles, and promote systemic inflammatory and metabolic signaling. These peripheral changes could interact with brain endothelial cells, glia, mitochondria, hippocampal neurogenesis, and synaptic-plasticity pathways. However, the proposed doxorubicin-gut-brain pathway remains a predominantly preclinical and incompletely tested framework. No longitudinal human study has yet established, within the same patients, the temporal sequence linking doxorubicin exposure, microbiome or metabolome changes, systemic inflammation, and objective cognitive outcomes. Existing animal studies also vary in dose, regimen, tumor context, sampling time, microbiome methodology, and control of behavioral or microbiological confounders, while causal rescue experiments remain limited. Key priorities are therefore longitudinal human cohorts with pretreatment baselines and repeated multi-omics and cognitive assessments; animal studies that test temporal precedence and causal rescue or pathway blockade in the same model; mediation analyses that determine whether microbial or metabolic changes lie between treatment and cognitive dysfunction; and mechanism-informed clinical trials that demonstrate target engagement, cognitive benefit, oncology safety, and preservation of antitumor efficacy. Microbiome-directed interventions are promising but remain investigational for doxorubicin-associated CICI.

blood–brain barrier↗

PubMed2004

Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats.

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL + BBS (10 microg/kg, s.c. x3), BDL + NT (300 microg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.

Alanine Transaminase↗