Co-fermentation of honeysuckle-Cassia seeds by Lactobacillus acidophilus and Bacillus subtilis: A new approach to attenuate alcohol-induced acute gastric mucosal damage and modulate immune response

Gastric Mucosal Damage by Ethanol Is Mediated by Substance P and Prevented by Ketotifen, a Mast Cell Stabilizer

Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a mast cell stabilizer

The Egyptian Journal of Histology 2011, 34:80–91 8 (1245 -2011) Aloe plants have been used medicinally for centuries. Recent widespread importance of commercial aloe vera has encouraged scientists to scientifically assess these products. Aim The aim of this study was to assess the possible protective role of oral commercial aloe vera on gastric mucosal acute damage induced by nonsteroidal anti-inflammatory drugs such as diclofenac sodium. Materials and methods Seventy adult male albino rats were divided randomly into four groups: group I (control), group II animals were given 200 mg/kg body weight of aloe vera once daily orally for 2 weeks, group III animals were administered a single oral dose of diclofenac sodium (80 mg/kg body weight) to induce acute gastric damage, group IV animals were given the same dose of aloe vera for 2 weeks followed by induction of acute gastric damage. Stomachs of animals of the four groups were studied macroscopically and microscopically. Morphometrical and statistical analyses were also carried out for determination of the percentage of area and depth of the mucosal lesion. Results This study showed that the percentage of area and depth of the mucosal lesions were significantly decreased in group IV in comparison with other groups. Microscopically, group IV and group III showed exfoliation of the surface epithelium, necrosis of some cells of the upper part of the gland, and loss of architecture of the basal part of the gland. Moreover, in group IV, periodic acid Schiff-Alcian blue-positive mucoussecreting cells appeared along the pits, neck, and isthmus with a thick periodic acid Schiff-Alcian blue-positive stained surface mucous film compared with a thin interrupted mucous film on the surface epithelium of the fundic mucosa in group III. Ultrathin sections showed predominance of mucous secretory cells with various types of mucoid granules in group IV. Conclusion Commercial aloe vera provides a degree of protection against acute gastric mucosal damage mainly by increasing mucin secretion.

The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats.

IntroductionIndomethacin is an anti-inflammatory drug with clearly known side effects on gastric mucosa. New treatment and side effect prevention methods are being studied. Donkey milk, as a nutritional support, has recently come into the spotlight with its anti-oxidant features, high antibody content and low allergenic properties. In this study, we investigated donkey milk’s possible protective effect against acute gastric mucosal damage by indomethacin.Material and methodsFour groups, each composed of 8 rats, were created. Rats in the first and third groups were fed with standard rat chow, while those in the second and fourth groups were additionally fed with 25 mg/kg of donkey milk per day via nasogastric gavage. On the 11th day gastric mucosal damage was induced by oral administration of 30 mg/kg of indomethacin to the rats in groups 3 and 4. Six h later all rats were sacrificed and their stomachs were removed for macroscopic and microscopic evaluation as well as biochemical examination of glutathione (GSH) and malondialdehyde (MDA) levels. Tumor necrosis factor-α (TNF-α) expression in the gastric mucosa was evaluated immunohistochemically.ResultsIn the donkey milk-indomethacin group, total area of erosion and degree of linear ulceration were significantly lower than in the standard food-indomethacin group (p < 0.05). Also, GSH levels were increased and MDA levels were decreased significantly in this group. Tumor necrosis factor-α expression was more prevalent and stronger in the gastritis group, while lower expression was observed in the donkey milk group.ConclusionsDonkey milk was observed to have significant protective effects against gastric damage induced by indomethacin.

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.

To elucidate the possible role of vasoactive intestinal peptide (VIP) in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 ml 96% ethanol with or without intravenous or intraperitoneal coadministration of VIP (1 nmol/liter to 1 mumol/liter/100 g). VIP was found to double the mean lesion area when compared with that induced by ethanol alone (P < 0.05), an effect that was prevented by VIP antagonist (1 mumol/liter/100 g). A substance P antagonist (1 mumol/liter/100 g) also reduced the extent of gastric damage induced by coadministration of VIP and ethanol. VIP antagonist or substance P antagonist significantly reduced ethanol-induced gastric mucosal damage. Gastric mucosal levels of LTB4, LTC4, VIP, and substance P were significantly increased in ethanol-treated rats as compared with saline-treated animals (P < 0.05). The augmentation of ethanol-induced damage by VIP was associated with increased gastric mucosal levels of LTB4. In VIP-treated rats, gastric mucosal levels of substance P were found to be significantly increased compared with control rats (P < 0.05). Administration of VIP to pyloric-ligated rats significantly increased gastric acid output and blood pepsinogen A levels as compared with saline treated rats (P < 0.05). Ketotifen, a mast cell stabilizer (100 micrograms/100 g), administered orally 30 min before damage induction by ethanol, with or without VIP, totally abolished the damage of the surface epithelium of the entire gastric mucosa and significantly reduced the mucosal levels of LTC4 and LTB4 (P < 0.05). It is suggested that VIP is involved in the pathogenesis of acute ethanol-induced gastric mucosal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Acetylsalicylic acid is in common clinical use but has the side effect of causing gastric mucosal erosions and selective injury to parietal cells. Aim: To explore if prior treatment with Prunus dulcis (almond) had a protective effect against acetylsalicylic acid induced injury. Study design: Experimental study. Methodology: Albino mice weighing 30 to 40 grams were given two drops of almond oil without peel and 300 mg of finely ground whole almond kernel by oral gavage for sixty days followed by 400 mg/kg body weight of acetylsalicylic acid orally. Gastric mucosal damage was observed and recorded as ulcer index. The number of parietal cells/ sq. micrometer and area of parietal cells were observed and recorded under microscope in formalin fixed H and E stained sections. Data analyzed by SPSS 22.0v. Results: Mucosal damage, distortion of gastric glands and damage to parietal cells was pronounced in the positive control animals. The number of surviving parietal cells after acetylsalicylic acid insult in animals given almond oil was significantly higher when compared with positive control animals (p&lt;0.001) and even better in animals receiving whole ground almond kernel. The area of parietal cells was also similarly larger in the treated animals. Conclusion: This study concluded Prunus dulcis offers protection against acute gastric mucosal injury and damage to the gastric parietal cells caused by acetylsalicylic acid in mice. Keywords: Prunus Dulcis, Parietal Cells, Gastric Erosions and Acetylsalicylic Acid.

PMK-S005 is synthetic s-allyl-L-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models. The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats. Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10mg/kg) or rebamipide (50mg/kg) 1h before administration of NSAIDs including aspirin (200mg/kg), diclofenac (80mg/kg), and indomethacin (40mg/kg). After 4h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1β, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis. Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1β production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5mg/kg, which were frequently superior to those of rebamipide. These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.

The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats.

Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin. Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant. As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05). Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties.

1. The role of leukotriene B4 (LTB4) and LTC4 as mediators of gastric mucosal damage following ethanol challenge in vivo has been investigated using two selective 5-lipoxygenase inhibitors, BW A4C and BW A137C. 2. Oral administration of ethanol to rats in vivo, induced macroscopic damage to the gastric mucosa and markedly increased the formation of the 5-lipoxygenase products, LTB4 and LTC4, from the mucosa ex vivo. 3. Pretreatment with the acetohydroxamic acids BW A4C and BW A137C (5-50 mg kg-1 p.o.) dose-dependently reduced ethanol-stimulated LTB4 and LTC4 formation by the gastric mucosa, with an ID50 of approximately 5 mg kg-1 p.o. 4. A single oral dose of BW A4C (20 mg kg-1) induced near-maximal inhibition of mucosal LTB4 formation within 30 min, which was well maintained for 5 h, whereas BW A137C (20 mg kg-1 p.o.) induced maximal inhibition between 30 and 60 min after administration, which then diminished over the subsequent 5 h. 5. The mucosal formation of the cyclo-oxygenase product, 6-keto-prostaglandin F1 alpha, which was unaltered following ethanol challenge, was not inhibited by the acetohydroxamic acids. Likewise, the small increase in mucosal thromboxane B2 formation following challenge was not inhibited by BW A4C. 6. Neither BW A4C nor BW A137C, at doses that almost completely inhibited the mucosal synthesis of LTB4 or LTC4, reduced the macroscopic gastric mucosal damage induced by ethanol. 7. Pretreatment with the lipoxygenase inhibitor BW 755C (5-50 mg kg-1 p.o.) did reduce mucosal damage, but there was a dissociation between the degree of protection and the inhibition of leukotriene biosynthesis. 8. Oral administration of high doses of either BW A4C or BW A137C (300mgkg-1) did not induce macroscopic gastric damage over a 3 h period. 9. These findings suggest that the leukotrienes, LTB4 and LTC4 are not the primary mediators of ethanol-induced acute mucosal damage, but do not exclude their role in more chronic gastric damage and inflammation.

Mucus is an important factor in the physiological defense mechanism of the gastrointestinal tract. We have reported that two distinct antigenicities reacting with anti-mucin monoclonal antibodies (mAbs), HCM31 and RGM26, emerged in epithelial cells regenerating from acetic acid-induced gastric damage in the rat. Here, we examined whether the expression of specific mucins occurred during the healing stage of acute gastric mucosal lesions, and what was the principal alteration of the mucus in the regenerating process of gastric epithelia from slight mucosal lesions. Eight-week-old male Wistar rats were used. The animals were administered 0.6 N hydrochloric acid, or 0.5% carboxymethyl cellulose sodium salt into their stomachs. Twenty-four, 48, and 72 h after the HCl administration, their stomachs were removed. Immunohistochemical observation was performed after staining with the mAbs, RGM21, RGM26, HIK1083, or HCM31. Twenty-four hours after the administration of HCl, mucous cells stained with RGM26 emerged in the deeper area of the surface epithelial cells in the damaged corpus mucosa. After 48 h, HCM31-positive cells were noted in the epithelial cells where the mucosal damage reached more deeply. The appearance of specific mucin species was observed in the regenerating epithelia of the rat during the healing process from acute gastric mucosal damage.

Gastric and intestinal injury induced by nonsteroidal anti-inflammatory agents (NSAIDs) such as aspirin (ASA) is a common side effect of this class of drugs, but the mechanism by which these drugs act is not fully explained. In this study the effects of 3 days of continuous oral ASA administration (1 g twice daily) to eight healthy male volunteers were studied. To estimate the extent of mucosal damage, gastroscopy was performed before and after 3 days of ASA treatment, during which the mucosal blood flow was measured by means of laser-Doppler flowmetry. Before each endoscopy gastric microbleeding was measured. Since neutrophil activation has recently been suggested to be involved in the pathogenesis of ASA-induced gastric mucosal damage, we examined the influence of ASA treatment on the activation of leukocytes by determining their association with platelets in the blood. Aspirin-induced acute gastric damage reached about 3.5 in the endoscopic Lanza score. Mucosal blood flow increased significantly after ASA treatment, by about 50% in the oxyntic gland area and by 87% in the antral area. Gastric microbleeding rose from about 0.38 ml/day in the intact stomach to about 7.7 ml/day after ASA treatment. The platelet/neutrophil adherence increased significantly in both thrombin-unstimulated and thrombin-stimulated platelets. We conclude that acute 3 days' administration of ASA in man produces well-defined areas of gastric damage accompanied by a significant increase in gastric microbleeding and gastric blood flow and that ASA promotes platelet/neutrophil adhesion that may resemble the neutrophil/endothelium interaction in the gastric mucosa.

Objective To observe the effect of preventively used moxibustion on the expression of apoptosis-related factors in rats with acute gastric mucosal damage (GMD), and analyze the relationship between those factors and heat shock protein 70 (HSP70), for discovering the mechanism of moxibustion for protecting gastric mucosa from the aspect of mitochondria signal transduction of apoptosis.