Gastric Mucosal Integrity Research Articles

Cyclooxygenase (COX)‐1/prostaglandins (PGs) and their receptors involved in modulating gastric mucosal integrity under stress conditions

Nonsteroidal anti‐inflammatory drugs themselves are not only ulcerogenic in the gastrointestinal mucosa but also potentiate the gastric ulcerogenic responses to various stimuli including stress. In the present study, we investigated the roles of COX isozymes/PGs and their receptors in the mucosal defense against cold‐restraint stress‐induced gastric lesions. Male C57BL/6 wild‐type (WT) mice and those lacking COX‐1 or COX‐2 as well as those lacking EP1‐, EP3‐ or IP‐receptors were used after 18 h fasting. The animals were restraint in ballman cages and kept in cold room at 10°C for 90 min. Cold‐restraint stress induced multiple gastric lesions in WT mice. These lesions were significantly worsened by pretreatment of indomethacin, loxoprofen or SC‐560, but not celecoxib. Likewise, these lesions were aggravated in the animals lacking COX‐1 but not COX‐2. The gastric ulcerogenic response to cold‐restraint stress was also aggravated in the animals lacking IP‐receptors but not EP1 or EP3 receptors. These results suggest that COX‐1/PGs play a crucial role in gastric mucosal defense during cold‐restraint stress, and this action is mediated mainly by the activation of IP receptors.

IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

Hydrogen sulphide (H2S) has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g). After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

Effect of Di(2-ethylhexyl)phthalate onHelicobacter pylori-Induced Apoptosis in AGS Cells

Plastic products are wildly used in human life. Di(2-ethylhexyl)phthalate (DEHP) is an essential additive in plastic manufacturing and is used as plasticizer for many products including plastic food packaging. DEHP is a teratogenic compound and can cause potent reproductive toxicity. DEHP can also cause liver damage, peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated with peptic ulcers and gastric cancer; however, the underlying effect and mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral infection route of H. pylori parallels the major ingestion route of DEHP into the human body. Therefore, we wanted to study the effect of DEHP and H. pylori exposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma). The viability of the AGS cell line was significantly lower in 80 μM-DEHP and H. pylori (MOI = 100 : 1) coexposure than DEHP or H. pylori alone. DEHP and H. pylori coexposure also induced caspase-3 activation, and increased Bax/Bcl-2 ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can enhance H. pylori cytotoxicity and induce gastric epithelial cell apoptosis. Therefore, it is possible that DEHP and H. pylori coexposure might enhance the disruption of the gastric mucosa integrity and potentially promote the pathogenesis of gastric carcinogenesis.

Activation of the bile acid receptor GPBAR1 protects against gastrointestinal injury caused by non-steroidal anti-inflammatory drugs and aspirin in mice.

Low doses of aspirin (acetylsalicylic acid; ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of gastrointestinal bleeding. GPBAR1 is a bile acid receptor expressed in the gastrointestinal tract. Here, we have investigated whether GPBAR1 was required for mucosal protection in models of gastrointestinal injury caused by ASA and NSAIDs. EXPERIMENTAL APPROCH: GPBAR1(+/+) and GPBAR1(-/-) mice were given ASA (10-50 mg.kg(-1)) or naproxen. Gastric and intestinal mucosal damage was assessed by measuring lesion scores. Expression of GPBAR1, mRNA and protein, was detected in mouse stomach. Mice lacking GPBAR1 were more sensitive to gastric and intestinal injury caused by ASA and NSAIDs and exhibited a markedly reduced expression of cystathionine-γ-liase (CSE), cystathionine-β-synthase (CBS) and endothelial NOS enzymes required for generation of H(2)S and NO, in the stomach. Treating GPBAR1(+/+) mice with two GPBAR1 agonists, ciprofloxacin and betulinic acid, rescued mice from gastric injury caused by ASA and NSAIDs. The protective effect of these agents was lost in GPBAR1(-/-) mice. Inhibition of CSE by DL-propargylglycine completely reversed protection afforded by ciprofloxacin in wild type mice, whereas treating mice with an H(2)S donor restored the protective effects of ciprofloxacin in GPBAR1(-/-) mice. Deletion of GPBAR1 altered the morphology of the small intestine and increased sensitivity to injury caused by naproxen. GPBAR1 is essential to maintain gastric and intestinal mucosal integrity. GPBAR1 agonists protect against gastrointestinal injury caused by ASA and NSAIDs by a COX-independent mechanism.

Effect of diet grinding and pelleting fed either dry or liquid feed on dry matter and pH in the stomach of pigs and the development of gastric ulcers

The physical form of diets has a marked impact on the development of gastric ulcers in pigs. Earlier studies showed effects of fine grinding and pelleting on the integrity of gastric mucosa as well as on local intragastric milieu. This study was conducted to evaluate the effects of dry or liquid feeding on intragastric milieu (DM and pH) in pigs. The 23 piglets were housed individually and fed with test diets and water ad lib for 6 wk. Both experimental diets [coarsely ground diet fed as mash (CM) vs. finely ground pelleted diet (FP)] were identical in ingredients (39.5% wheat, 34% barley, 20% soybean meal) and chemical composition and were either offered dry or in liquid (25% DM) form. At the end of the trial the animals were slaughtered; the stomach was removed and samples were taken from different localizations. Feeding diets dry or liquid had no effect on the pH (P > 0.05). The diet noticeably affected the gastric content. The FP diets resulted in a more liquid chyme (P < 0.05), and the intragastric pH did not differ between regions. Feeding CM caused marked effects of localization regarding pH (highest values: pars nonglandularis; lowest values: fundus). None of the pigs fed CM showed signs of gastric ulcers, but the score was markedly higher (P < 0.05) when pigs were fed FP. Therefore the predominant factor for development of gastric ulcers seems to be the structure (particle size) of the diet.

Gastric Cytoprotection Beyond Prostaglandins: Cellular and Molecular Mechanisms of Gastroprotective and Ulcer Healing Actions of Antacids

This article updates current views on gastric mucosal defense, injury, protection and ulcer healing with a focus on mucosal protective and ulcer healing actions of antacids. The gastric mucosa is continuously exposed to a variety of noxious factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids, lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others. Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post-epithelial defense mechanisms permitting the mucosa to withstand exposure to the above damaging factors. When mucosal defense is weakened or overwhelmed by injurious factors, injury develops in the form of erosions or ulcers. In the late 1970s Andre Robert and coworkers discovered that microgram amounts of a prostaglandin E2 analog protects the gastric mucosa against a variety of ulcerogenic and necrotizing agents - even such strong inducers of injury as 100% ethanol and boiling water. They proposed a new concept of cytoprotection. Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal growth factor were shown to exert protective action on gastric mucosa. Additionally, some antacids have been shown to exert a potent mucosal protective action against a variety of injurious factors and accelerate healing of erosions and gastric ulcers. These actions of antacids, especially hydrotalcite - the newest and the most extensively studied antacid - are due to activation of prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H. pylori toxins; induction of heat shock proteins; and, activation of genes encoding growth factors and their receptors.

Gastric Mucosal Protection And Central Nervous System

Several human and experimental data suggest the particular importance of gastric protective processes in maintaining mucosal integrity. Both peripheral and central mechanisms are involved in this process. In the periphery, pre-epithelial mucus-bicarbonate layer, mucus, phospholipids, trefoil peptides, prostaglandins, heat shock proteins, sensory neuropeptides, nitric oxide, and hydrogen sulfide may mediate mucosal protection. In the central nervous system hypothalamus and dorsal vagal complex (DVC) have particular important role in the regulation of centrally-induced gastroprotection. Stimulation of paraventricular nuclei either aggravates or inhibits the mucosal injury depending on the ulcer model. Vagal nerve also has a dual role, its activation can induce mucosal injury (by high dose of thyrotropin- releasing hormone (TRH), electrical stimulation), however, integrity of vagal nerve is necessary for gastroprotection induced either peripherally (by PGE2, prostacyclin, adaptive cytoprotection), or centrally (e.g. by neuropeptides). The centrally induced gastroprotection is likely to be vagal dependent, though vagal independent pathways have also been shown. Endomorphin-1 and endomorphin-2, selective μ-opioid receptor ligands, proved to be highly potent and effective gastroprotective agents in ethanol ulcer model (0.03-3 pmol intracerebroventricularly). Inhibition of the degradation of endomorphins by diprotin A resulted in gastroprotective effect, indicating the potential role of these endogenous opioids in the regulation of gastric mucosal integrity. Endomorphin-2 injected intracerebroventricularly restored the reduced levels of CGRP and somatostatin in gastric mucosa induced by ethanol. In conclusion, neuropeptides expressed in dorsal vagal complex and hypothalamus may have a regulatory role in maintaining gastric mucosal integrity by stimulating the formation of mucosal protective compounds. Keywords: Gastric Mucosal Protection, Peripheral, Central Mechanism, Neuropeptides, Endomorphins, mucus, phospholipids, prostaglandins, heat shock proteins, hypothalamus

Gastric Mucosal Protection And Central Nervous System

Several human and experimental data suggest the particular importance of gastric protective processes in maintaining mucosal integrity. Both peripheral and central mechanisms are involved in this process. In the periphery, pre-epithelial mucus-bicarbonate layer, mucus, phospholipids, trefoil peptides, prostaglandins, heat shock proteins, sensory neuropeptides, nitric oxide, and hydrogen sulfide may mediate mucosal protection. In the central nervous system hypothalamus and dorsal vagal complex (DVC) have particular important role in the regulation of centrally-induced gastroprotection. Stimulation of paraventricular nuclei either aggravates or inhibits the mucosal injury depending on the ulcer model. Vagal nerve also has a dual role, its activation can induce mucosal injury (by high dose of thyrotropin- releasing hormone (TRH), electrical stimulation), however, integrity of vagal nerve is necessary for gastroprotection induced either peripherally (by PGE2, prostacyclin, adaptive cytoprotection), or centrally (e.g. by neuropeptides). The centrally induced gastroprotection is likely to be vagal dependent, though vagal independent pathways have also been shown. Endomorphin-1 and endomorphin-2, selective μ-opioid receptor ligands, proved to be highly potent and effective gastroprotective agents in ethanol ulcer model (0.03-3 pmol intracerebroventricularly). Inhibition of the degradation of endomorphins by diprotin A resulted in gastroprotective effect, indicating the potential role of these endogenous opioids in the regulation of gastric mucosal integrity. Endomorphin-2 injected intracerebroventricularly restored the reduced levels of CGRP and somatostatin in gastric mucosa induced by ethanol. In conclusion, neuropeptides expressed in dorsal vagal complex and hypothalamus may have a regulatory role in maintaining gastric mucosal integrity by stimulating the formation of mucosal protective compounds.

Effects of Meloxicam and Phenylbutazone on Equine Gastric Mucosal Permeability

Newer NSAIDs that more selectively target the induced isoform of the cyclooxygenase enzyme (COX2) activity might reduce adverse effects while preserving therapeutic benefits of these drugs. To compare the effect of oral administration of multiple dose rates of meloxicam and phenylbutazone (PBZ) on gastric mucosal integrity in horses. Twenty-five light breed horses. In vivo toxicity study. Horses were randomly assigned to 5 treatment groups, receiving placebo, PBZ (4.4 mg/kg PO q12h day 1, 2.2 mg/kg PO q12h for 4 days, 2.2 mg/kg PO q24h for 9 days), or 3 dose rates of meloxicam (0.6 mg/kg q24h, 1.8 mg/kg q24h, 3.0 mg/kg q24h) for 14 days. Sucrose permeability testing was performed on Day 0 (before treatment) and on Day 13. All personnel involved with data collection or analysis were blinded to treatment. Administration of PBZ at the above dose rate significantly increased gastric permeability to sucrose, evidenced by increased peak serum sucrose concentrations (280-1,580 pg/μL, P = .001) after treatment. Similar changes were not evident after administration of meloxicam at any dose rate tested, or in control horses (P > .05). Treatment was not associated with significant differences in ulceration of the squamous or glandular mucosa. Peak sucrose concentrations were not correlated with serum total protein or albumin concentrations (R(2) = -0.07, P = .61, R(2) = -0.08, P = .58, respectively). These results suggest that PBZ was associated with greater compromise to gastric mucosal integrity than meloxicam.

Experimental research Effects of captopril on factors affecting gastric mucosal integrity in aspirin-induced gastric lesions in Sprague-Dawley rats

IntroductionCaptopril is an angiotensin-converting enzyme inhibitor, which is used as an antihypertensive agent and has shown antioxidant properties. This study aims at determining the effects of captopril on factors affecting gastric mucosal integrity in aspirin-induced gastric lesions.Material and methodsEighteen male Sprague-Dawley (200-250 g) rats that were given aspirin (40 mg/100 g body weight) were divided into three groups: the control, captopril (1 mg/100 g body weight daily) and ranitidine (2.5 mg/100 g body weight twice daily) groups. Ranitidine and captopril were given orally for 28 days. Rats in all groups were sacrificed and the parameters measured.ResultsCaptopril reduced gastric acidity, and increased gastric glutathione (GSH) and prostaglandin E2 (PGE2) significantly in comparison to the control group. Captopril also reduced malondialdehyde (MDA) and gastric lesions insignificantly compared to the control group. Ranitidine healed the lesions significantly compared to the control group. There was no difference between ranitidine and captopril on the severity of lesions, gastric acidity, MDA and GSH. Captopril increased PGE2 compared to ranitidine (p < 0.05).ConclusionsCaptopril has desirable effects on the factors affecting gastric mucosal integrity (acidity, PGE2 and GSH) and is comparable to ranitidine in ulcer healing.

Dietary agonists of TRPV1 inhibit gastric acid secretion in mice.

Capsaicin and 6-gingerol, pungent components of chilli pepper and ginger, are known as dietary agonists of transient receptor potential vanilloid-1. Transient receptor potential vanilloid-1 nerve fibers are recognized to play a role in gastric mucosal integrity in rats. In the present studies, we examined the acute effects of peroral administration of capsaicin and 6-gingerol on gastric acid secretion in conscious mice. These agents were given p. o. 30 min before the pylorus was ligated. Oral administration of capsaicin (1.0-100 mg/kg) or 6-gingerol (1.5-50 mg/kg) significantly and dose-dependently inhibited basal acid secretion. Pretreatment with BCTC, a transient receptor potential vanilloid-1 antagonist, significantly reversed the reduced basal acid secretion by capsaicin or 6-gingerol. The combination of the lowest doses of capsaicin and 6-gingerol markedly inhibited basal acid secretion in conscious mice and this was also significantly reversed by BCTC. Moreover, the combination of the maximal dose of capsaicin and 6-gingerol inhibited basal acid secretion only to the level of a single administration of the maximal dose of capsaicin. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on the inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1. In separate experiments, intraduodenal administration of either capsaicin (30 mg/kg) or 6-gingerol (15 mg/kg), whose doses were observed to have a significant inhibitory effect by oral administration, tended to inhibit basal acid secretion compared with the vehicle. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1, and oral administration of transient receptor potential vanilloid-1 agonists directly stimulates transient receptor potential vanilloid-1 in the gastric lumen, resulting in a potent reduction of gastric acid secretion.

Effect of feed processing on growth performance and gastric mucosa integrity in pigs from weaning until slaughter

The effect of technological treatments on the performances from 1 week after weaning until slaughter and on the gastric mucosa integrity of growing-finishing pigs at slaughter was investigated. We compared a diet expanded at high pressure and temperature (expandate) with a diet expanded under milder conditions that was subsequently pelleted and crumbled (crumble) and an untreated control diet (meal). At weaning, a total of 180 pigs (8.4±0.8kg) were divided over 30 pens of 6 animals, with 10 pens per treatment. Feed structure had a clear impact on performance results. However, while the expanded and the crumbled feed was used more efficiently (P=0.003), feed intake was considerably higher on the meal feed (P=0.003). Between start and slaughter, this led to a similar growth in the three groups (P=0.898). Apparent faecal digestibility of dry matter (P=0.843) or crude protein (P=0.726) did not differ between the diets. The ulcer score was affected by the feed structure (P<0.001). Pigs on the meal diet had the lowest ulcer score, those on the expandate an intermediate score and those on the crumbled diet the highest score, with all diets being significantly different from each other (P<0.05). The number of Helicobacter suis bacteria per gram of mucus was lower on the meal than on the expandate or the crumbled feed.In conclusion, it can be stated that expanding and pelleting improved feed efficiency of growing-finishing pigs. However, these technological treatments had a negative impact on gastric mucosa integrity and were associated with an increased H. suis colonisation.

Transmural Pressure Loading Enhances Gastric Mucosal Cell Proliferation

Although increased intraluminal pressure in the stomach due to gastric outlet obstruction or functional gastric motor dysfunction, including gastroparesis, may affect gastric mucosal integrity, the direct effect of mechanical pressure on gastric mucosal cells has not yet been fully investigated. The aims of this study were to determine whether exposure to transmural pressure would affect the proliferation of gastric mucosal cells and to elucidate the intracellular signaling pathways involved. Cellular proliferation and DNA synthesis were evaluated in rat gastric epithelial cells exposed to high transmural pressures. The levels of activation of 3 MAP kinases, ERK, JNK, and p38, were assessed, and the induction of immediate early gene expression was examined. The activation of nuclear factor activator protein-1 (AP-1) was evaluated by an electrophoretic mobility shift assay. Exposure to high transmural pressure significantly increased DNA synthesis within 24 h, with the most marked increase observed after exposure to a pressure of 80 mmHg, and this increase was inhibited by the MEK1 inhibitor PD98059. Early activation of ERK kinase, but not of JNK or p38 kinase, was detected after pressure loading. Early induction of the c-fos and c-myc genes and activation of the AP-1 transcription factor were also demonstrated within 3 h of exposure to 80 mmHg of pressure. Gastric mucosal cell proliferation induced by exposure to high transmural pressure may be related to early activation of ERK, the induction of c-fos and c-myc, and the activation of AP-1.

Biphasic effects of H. pylori infection on low-dose aspirin-induced gastropathy depending on the gastric acid secretion level

The association of Helicobacter pylori infection with aspirin-induced gastropathy is controversial. H. pylori infection exerts diverse effects on gastric acid secretion. In this study, the interaction between H. pylori infection and aspirin was investigated with reference to the individual gastric acid secretion level in H. pylori-positive subjects. Ninety-three (81 men, mean age: 70 years) long-term low-dose aspirin takers were prospectively enrolled. H. pylori infection was evaluated by serum IgG antibody determination, and gastrin-stimulated acid output was assessed with the endoscopic gastrin test. H. pylori-positive aspirin-takers were classified into 2 subgroups (hyposecretors and non-hyposecretors). The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score; intensive aspirin-induced gastropathy was defined as a modified Lanza score of ≥4. Multiple logistic regression analyses were used to adjust for potential confounders. With H. pylori-negative patients taken as the reference, H. pylori infection was found to be positively associated with intensive gastropathy among non-hyposecretors, with an odds ratio (OR) (95 % confidence interval [CI]) of 4.2 (1.1-17.1), while the infection was negatively associated with gastropathy among hyposecretors, with an OR (95 % CI) of 0.3 (0.08-0.9). Aspirin-induced gastropathy occurred preferentially in the antrum among H. pylori-positive non-hyposecretors, while it affected the fundus among H. pylori-positive hyposecretors. The effect of H. pylori infection on the aspirin-induced gastropathy was biphasic depending on the individual gastric acid secretion level. In the presence of sufficient amounts of gastric acid, H. pylori infection and aspirin could synergistically damage gastric mucosal integrity, while in the absence of sufficient amounts of gastric acid, the synergistic effect could be completely counteracted and the infection could even suppress the aspirin-induced gastropathy.

Effects of captopril on factors affecting gastric mucosal integrity in aspirin‐induced gastric lesions in Sprague‐Dawley rats

Captopril, an angiotensin converting enzyme inhibitor, used as an antihypertensive agent has been shown to have antioxidant properties which prompted the present study. This study investigated the effects of captopril on factors affecting gastric mucosal integrity in rats that had aspirin‐induced gastric lesions. Eighteen male Sprague‐Dawley (200–250g) rats given aspirin (40 mg/100g bw) were divided into a control group, captopril (1 mg/100g bw daily) and ranitidine (2.5 mg/100g bw bidaily) groups. Oral ranitidine and captopril were given for 28 days. Compared with the control group, captopril reduced gastric acidity (P&lt;0.05), increased gastric GSH (P&lt;0.05) and prostaglandin E2 (P&lt;0.05). Ranitidine healed the lesions significantly (P&lt;0.05) compared to the control group. There was, however no difference between ranitidine and captopril on the severity of lesions, gastric acidity, MDA and GSH. Captopril increased PGE2 compared to ranitidine (P&lt;0.05). In conclusion, we found that captopril produced desirable effects on gastric acidity, PGE2 and GSH. Its capability to enhanced gastroprotective protective parameters and reduce the aggressive acid‐factor optimises the balance between protective and aggressive factors. In view of this linkage, we strongly suggest captopril as a potential novel antiulcer agent. Research was funded by the Faculty of Medicine, Universiti Kebangsaan Malaysia.

Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.

Formulation and evaluation of oil entrapped floating beads of Piperine for peptic ulcers

Spices have become the source of therapy in most of the countries and are especially commonly used in India where herbs and spices are the indigenous part of the curing system. From previous studies, spices are known to have digestive stimulant actions and thus may be helpful in treating the digestive disorders.[1, 2] Piperine, the most common spice of Indian kitchen, has previously been shown to have the anti ulcer activity. [3,4,5] Piperine was found to be effective for gastric ulcers in rats and mice at a dose range of 25 to 100 mg/kg.[6] Apart from its gastro protective activity, piperine has also been investigated for other beneficial gastro intestinal effects including antileishamnial activity,[7] antidiarrheal activity,[8] improved gastric mucosal integrity,[9] muco-protective activity[10] and hepato protection,[11] along with the improved absorption[12] and bio availability[13] of several classes of drugs.

Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats.

T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol-induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats.

Association of gastric acid and mucus secretion level with low-dose aspirin-induced gastropathy

Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication.

Effect of particle size distribution and dietary crude fibre content on growth performance and gastric mucosa integrity of growing–finishing pigs

This study was designed to examine the effect of crude fibre (CF) content and particle size of the diet on growth performance, carcass yield and gastric mucosa integrity. The experimental design was a 2×2 factorial trial with 192 pigs fed from 24 to 110 kg bodyweight. Four diets were compared: (1) low fibre finely ground; (2) low fibre coarsely ground; (3) high fibre finely ground; and (4) high fibre coarsely ground. All ingredients were ground before mixing. The high fibre coarsely ground diet resulted in the fewest lesions in the gastric pars oesophagea (P<0.001). Coarse grinding also resulted in the lowest urease activity in the stomach (P=0.006). The feed conversion ratio was worse on the coarsely ground diet than on the finely ground diet (P=0.038), whereas carcass yield was lower for pigs on the high fibre diet vs. the low fibre diet (P<0.001). Coarse grinding feed ingredients in a growing pig diet that is high in CF may reduce macroscopic lesions of the pars oesophagea but such a diet was accompanied in this study by inferior carcass yield.