Acute Gastric Injury Research Articles

Anti-Inflammatory Thioredoxin Family Proteins for Medicare, Healthcare and Aging Care.

Human thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, which is induced by biological stress due to oxidative damage, metabolic dysfunction, chemicals, infection/inflammation, irradiation, or hypoxia/ischemia-reperfusion. Our research has demonstrated that exogenous TRX is effective in a wide variety of inflammatory diseases, including viral pneumonia, acute lung injury, gastric injury, and dermatitis, as well as in the prevention and amelioration of food allergies. Preclinical and clinical studies using recombinant TRX (rhTRX) are now underway. We have also identified substances that induce the expression of TRX in the body, in vegetables and other plant ingredients. Skincare products are being developed that take advantage of the anti-inflammatory and anti-allergic action of TRX. Furthermore, we are currently engaged in the highly efficient production of pure rhTRX in several plants, such as lettuce, grain and rice.

Insect tea attenuates hydrochloric acid and ethanol-induced mice acute gastric injury.

The aim of the present study was to investigate the protective effect of insect tea on HCl/ethanol-induced gastric ulcers in ICR mice. The serum levels of vasoactive intestinal peptide, substance P, somatostatin, motilin and endothelin-1 in mice were assessed using commercial kits and gastric tissues of superoxide dismutase (SOD, nitric oxide (NO) and malondialdehyde (MDA) were determined using western blot analysis Insect tea significantly reduced HCl/ethanol-induced gastric juice secretion and increased the pH of gastric juice (P<0.05). Insect tea treatment signfiicantly increased vasoactive intestinal peptide and somatostatin, and significantly decreased motilin, substance P and endothelin levels in the serum (P<0.05). Treatment with insect tea was demonstrated to significantly increase levels of gastric SOD and NO and to reduce levels of MDA in the gastric ulcer mouse model (P<0.05). The gastric expression of inhibitor of nuclear factor-κB (NF-κB), epidermal growth factor (EGF), EGF receptor, neuronal nitric oxide synthase (nNOS), endothelial NOS, Mn-SOD, Cu/Zn-SOD and catalase was significantly increased in mice treated with inset tea compared with untreated model mice (P<0.05). Levels of NF-κB, and inducible NOS were demonstrated to be decreased in mice treated with insect tea compared with untreated model mice (P<0.05). The results of the present study suggest that insect tea has a protective effect against HCl/ethanol-induced gastric ulcers in ICR mice. This effect may be achieved via modulating serum neuropeptide levels, reducing gastric juice secretion, and modulating the inflammation- and antioxidant-associated protein expressions in gastric tissue.

The Regulatory Effects of Lateral Hypothalamus Area GABAB Receptor on Gastric Ischemia-Reperfusion Injury in Rats.

HIGHLIGHTS The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats.The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain.This work would provide a new therapeutic strategy for acute gastric injury.Gastric ischemia-reperfusion (GI-R) injury progression is largely associated with excessive activation of the greater splanchnic nerve (GSN). This study aims to investigate the protective effects of GABAB receptor (GABABR) in the lateral hypothalamic area (LHA) on GI-R injury. A model of GI-R injury was established by clamping the celiac artery for 30 min and then reperfusion for 1 h. The coordinate of FN and LHA was identified in Stereotaxic Coordinates and then the L-Glu was microinjected into FN, GABAB receptor agonist baclofen, or GABAB receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABABR, P-GABABR, NOX2, NOX4, and SOD in the LHA was detected by western blot, PCR, and RT-PCR. The expression of IL-1β, NOX2, and NXO4 in gastric mucosa was detected by western blot. We found that microinjection of L-Glu into the FN or GABAB receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABAB receptor antagonist CGP35348 reversed the protective effects of FN stimulation or baclofen into the LHA. Microinjection of baclofen into the LHA obviously reduced the expression of inflammatory factor IL-1β, NOX2, and NOX4 in the gastric mucosa.Conclusion: The protective effects of microinjection of GABABR agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the LHA.

Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach

ObjectiveLrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse...

Acute Gastric Injury Caused by Undissolved Sodium Picosulfate/Magnesium Citrate Powder.

Sodium picosulfate/magnesium citrate (SPMC) is a widely used oral bowel cleansing agent considered to be relatively safe. However, partially dissolved or undissolved SPMC powder may cause severe injuries of the esophagus and stomach. We report a very rare case of acute gastric injury without esophageal damage caused by the ingestion of undissolved SPMC powder. A 69-year-old man experienced epigastric pain after swallowing SPMC powder without dissolving it in water in preparation for a screening colonoscopy. He realized his mistake immediately and subsequently drank 2 L of water. The esophagogastroduodenoscopy conducted after 12 hours indicated an acute gastric ulceration without injury of the esophagus or duodenum. The endoscopy conducted after 6 weeks of oral proton pump inhibitor treatment showed healing of the gastric injury. This suggested that drinking large amounts of water after ingesting partially dissolved or undissolved SPMC powder can prevent serious esophageal injury, but offers no preventive benefit for acute gastric injury.

Role of vitamin D3 combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells.

BackgroundGastric diseases are a worldwide problem in modern society, as reported in the USA, in the range of 0.5–2 episodes/year/person and an incidence of 5–100 episodes/1000/week according to seasons and age. There is convincing evidence that oxidative stress is involved in the pathogenesis of acute gastric injury. Acid secreted from gastric parietal cells determines mucosal injuries which in turn cause inflammation and oxidative stress. Consequent inflammation produces free radicals by mitochondria thus causing lipid peroxidation, oxidative and acidic stress, which can lead to cell apoptosis. Vitamin D3, the active form of vitamin D, may counteract intracellular cell death and improve epithelial regeneration.MethodsThis study was planned to assess whether vitamin D3 is a protective factor against acid injury and oxidative stress in gastric epithelial cells. Primary epithelial cells and GTL-16 cells have been used to test the effects of Grisù® alone or in combination with vitamin D3 during oxidative stress or high acid exposition measuring cell viability, ROS production, cellular adhesion time along with apoptotic, autophagic and survival pathways. The combined effect of Grisù® and vitamin D3 was found more effective in counteracting the negative consequences of oxidative stress and acidity conditions than some other gastroprotective agents, such as Maalox® or Gaviscon®.ResultsIn case of oxidative stress or acidity condition the stimulation with Grisù® alone caused an improvement of cell viability and a reduction of ROS production on epithelial gastric cells. In addition, the adhesion time of the cells was improved. All these effects were increased by the presence of vitamin D3. Similar data were also observed in primary gastric epithelial cells confirming the results obtained in GTL-16 cells.ConclusionsThese results suggest that Grisù® in combination with vitamin D3 may exert a gastroprotective effect to maintain or restore the integrity of gastric epithelium through an antioxidant pathway, inhibiting apoptosis and activating survival kinases. Moreover, the combination of Grisù® and vitamin D3 improves cell viability and decreases ROS production compared to other gastroprotective agents combined with vitamin D3. All these data were validated using primary cells isolated from gastric tissue.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0543-z) contains supplementary material, which is available to authorized users.

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

Background/AimsDA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury.MethodsRats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway.ResultsThe inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression.ConclusionsDA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Syzygium aromaticum water extract attenuates ethanol‑induced gastric injury through antioxidant effects in rats.

The aim of the present study was to investigate whether Syzygiumaromaticum water extract (SAWE) has a protective effect against ethanol‑induced gastric injury in rats. Acute gastric injury was induced via intragastric administration of absolute ethanol at a dose of 5ml/kg. SAWE (250or500mg/kg/day) or cimetidine (100mg/kg/day), which was used as a positive control, were administered to the rats 2h prior to ethanol administration for 3days. All rats were sacrificed 24h following the final ethanol administration. To examine whether SAWE has a gastroprotective effect, assays were performed to assess the contents of malondialdehyde (MDA) and glutathione (GSH), the activities of catalase, glutathione‑S‑transferase and superoxide dismutase, and an immune-linked immunosorbent assay was performed for prostaglandin E2 (PGE2) production in gastric tissues by hematoxylin and eosin and periodic acid-Schiff staining. Histological assessment of the gastric wall was performed. Compared with ethanol treatment alone, treatment with SAWE at a dose of 250mg/kg/day significantly decreased the gastric MDA content and increased the GSH content, catalase activity, and production of gastric PGE2. Histological assessment showed that SAWE attenuated inflammatory cell infiltration and the loss of epithelial cells. These findings suggested that SAWE protected against ethanol‑induced gastric mucosal injury in the rats. These effects appeared to be associated with antioxidant activity, activation of the production of PGE2, suppression of inflammatory cell infiltration and loss of epithelial cells in the gastric mucosa. Collectively, SAWE may be beneficial in the prevention of gastric disease associated to oxidative stress.

The caspase-1 inhibitor AC-YVAD-CMK attenuates acute gastric injury in mice: involvement of silencing NLRP3 inflammasome activities.

This study evaluated the protective effects of inhibiting caspase-1 activity or gastric acid secretion on acute gastric injury in mice. AC-YVAD-CMK, omeprazole, or vehicle were administered to mice before cold-restraint stress- or ethanol-induced gastric injury. Survival rates and histological evidence of gastric injury of mice pretreated with AC-YVAD-CMK or omeprazole, and exposed to cold-restraint stress, improved significantly relative to the vehicle group. The increased levels of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18 following cold-stress injury were decreased by AC-YVAD-CMK, but not omeprazole, pretreatment. The increased expression of CD68 in gastric tissues was inhibited significantly by AC-YVAD-CMK pretreatment. Inhibiting caspase-1 activity in the NLRP3 inflammasome decreased gastric cell apoptosis, and the expression of Bax and cleaved caspase-3. AC-YVAD-CMK pretreatment significantly inhibited cold-restraint stress-induced increases in the expression of phosphorylated IκB-alpha and P38. General anatomy and histological results showed the protective effect of AC-YVAD-CMK on ethanol-induced acute gastric injury. Overall, our results showed that the caspase-1 inhibitor AC-YVAD-CMK protected against acute gastric injury in mice by affecting the NLRP3 inflammasome and attenuating inflammatory processes and apoptosis. This was similar to the mechanism associated with NF-κB and P38 mitogen-activated protein kinase signalling pathways.

Mo1252 Acute Gastric Injury after Highly Concentrated Glucose Ingestion Inversely Related With the Positivity to Breath Test

Mo1252 Acute Gastric Injury after Highly Concentrated Glucose Ingestion Inversely Related With the Positivity to Breath Test

Protective Effects of Manassantin A against Ethanol-Induced Gastric Injury in Rats.

Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

Quercetin protects gastric epithelial cell from oxidative damage in vitro and in vivo

Epithelial injury caused by reactive oxygen species (ROS) including H2O2 plays a critical role in the pathogenesis of gastric disorders. Therefore, pharmacological intervention targeting reactive oxygen species elimination has highly clinical values in therapy of gastric diseases. Although quercetin has been found to possess gastroprotective activity, whether it has a protective activity againress related injury to gastric epithelial cells remains unknown. The aim of the study is herein to investigate a possible protective effect of quercetin against oxidative stress in vitro and vivo. Human gastric epithelial GES-1 cells were pretreated with quercetin and then challenged with H2O2. In vivo reactive oxygen species production in acute gastric mocosa injury was assessed using a chemiluminescent probe L-012 (8-amino-5-chloro-7-phenylpyrido [3,4-d]pyridazine-1,4-(2H,3H)dione) after quercetin was administered to mice. In GES-1 cells, pretreatment of quercetin can significantly diminish H2O2-induced cell viability loss; decrease intracellular reactive oxygen species and Ca2+ influx; restore H2O2-induced ΔΨm dissipation. It also upregulates peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) expression under the state of oxidative stress, and the downstream cell apoptosis significantly decreased. In vivo, chemiluminescence imaging shows that quercetin attenuates reactive oxygen species production and gastric damages in acute gastric mucosal injury. We first reported the evidence that quercetin can protect gastric epithelial GES-1 cells from oxidative damage and ameliorate reactive oxygen species production during acute gastric mucosal injury in mice. This might be ascribed to its inhibition of oxidative stress, regulation of mitochondrial dysfunction, initiation of antioxidant defense and inhibition of apoptosis.

Involvement of glutamate–cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury

Large-dose or long-term use of aspirin tends to cause gastric mucosa injury, which is recognized as the major side effect of aspirin. It has been demonstrated that glutamate exerts a protective effect on stomach, and the level of glutamate is critically controlled by cystine/glutamate transporter (Xc−). In the present study, we investigated the role of glutamate–cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury in vitro and in vivo. Results showed that in human gastric epithelial cells, aspirin incubation increased the activity of LDH and the number of apoptotic cells, meanwhile down-regulated the mRNA expression of Xc− accompanied with decreased glutamate release. Similar results were seen in a rat model. In addition, exogenous l-glutamate attenuated the gastric mucosa injury and cell damage induced by aspirin both in vitro and in vivo. Taken together, our results demonstrated that acute gastric mucosa injury induced by aspirin is related to reduction of glutamate–cystine/glutamate transporter system activity.

Tu1246 The Effect of Eupatillin on Indomethacin Induced Small Intestinal Injury and Intestinal Permeability

Background: Eupatilin has pronounced antiinflammatory activities and exhibits cytoprotective effects in acute gastric injury model. Here we would like to investigate the possible role of protective effects on small intestine in indomethacin induced small intestinal damage model and their effect on intestinal permeability. Methods: Small intestinal damage was induced with indomethacin (15mg/kg). Rats in the treatment group received eupatilin (30 mg/kg) from day 0 to 3, and indomethacin from day 1 to 2 through intragastric lavage. On the contrary, rats in the control group received indomethacin only from day 1 to 2. On the fourth day, Rats were sacrificed, and small intestine was examined to compare the severity of inflammation in both groups by H&E stain. Intestinal permeability was evaluated by Fluorescein isothiocyanate (FITC)-labeled dextran. Western blot was performed to comfirm the association of eupatillin with ERK pathway in the prevention of small intestinal injury. Results: The inflammation score in the Eupatilin group was low compared with that in the indomethacin only group. Intestinal permeability evaluated by Fluorescein isothiocyanate(FITC)-labeled dextran was low in Eupatilin group compared to indomethacin only group(16204.2±13832.1 vs 30403.7±24012.6 , p value <0.05). Western blots revealed eupatilin enhanced the phosphorylation of extracellular signal-regulated kinase (p-ERK) expression in small bowel mucosa. Conclusion: Eupatilin is effective in the prevention of intestinal mucosal injury and prevents the increase of intestinal permeability by enhancing restitution of RIE cells via ERK activation.

Tu1248 Ursodeoxycholic Acid Modulates Cell-Cell Adhesion Molecules to Reduce the Intestinal Permeability in Inflammatory Bowel Disease

Background: Eupatilin has pronounced antiinflammatory activities and exhibits cytoprotective effects in acute gastric injury model. Here we would like to investigate the possible role of protective effects on small intestine in indomethacin induced small intestinal damage model and their effect on intestinal permeability. Methods: Small intestinal damage was induced with indomethacin (15mg/kg). Rats in the treatment group received eupatilin (30 mg/kg) from day 0 to 3, and indomethacin from day 1 to 2 through intragastric lavage. On the contrary, rats in the control group received indomethacin only from day 1 to 2. On the fourth day, Rats were sacrificed, and small intestine was examined to compare the severity of inflammation in both groups by H&E stain. Intestinal permeability was evaluated by Fluorescein isothiocyanate (FITC)-labeled dextran. Western blot was performed to comfirm the association of eupatillin with ERK pathway in the prevention of small intestinal injury. Results: The inflammation score in the Eupatilin group was low compared with that in the indomethacin only group. Intestinal permeability evaluated by Fluorescein isothiocyanate(FITC)-labeled dextran was low in Eupatilin group compared to indomethacin only group(16204.2±13832.1 vs 30403.7±24012.6 , p value <0.05). Western blots revealed eupatilin enhanced the phosphorylation of extracellular signal-regulated kinase (p-ERK) expression in small bowel mucosa. Conclusion: Eupatilin is effective in the prevention of intestinal mucosal injury and prevents the increase of intestinal permeability by enhancing restitution of RIE cells via ERK activation.

Su1948 In Vivo, Real Time Non-Invasive Assessment of Gastric Mucosal Injury Using Confocal Laser Endomicroscopy: Focus on Mucosal Microvessels, Progenitor Cells and Mucosal Protection. Direct Comparison With Quantitative Histology and Electron Microscopy.

Background/Aims: Studies of gastric mucosal injury and healing rely on macroscopic and histological assessment of fixed stomach specimens, which may not fully reflect in vivo events. As a result, the cellular targets and real time sequence of gastric mucosal injury are not fully defined. Confocal laser endomicroscopy (CLE), a novel cutting edge technology, has enabled in vivo real-time visualization of mucosal structures at a subcellular resolution. This study was aimed to: 1) assess acute gastric injury in real time using CLE with a focus on mucosal microvessels and progenitor cells; 2) determine whether hydrotalcite (HTL), the newest generation antacid, can protect gastric mucosa against ethanol injury; and, 3) identify the mechanisms involved. Methods: Fischer F344 rats received 1 ml 0.5% fluorescein i.v. followed by intragastric (i.g.) ethanol (1 ml, 50%) or saline. In some rats, either 1 ml of vehicle or HTL (20mg/kg) was given i.g. 30 min prior to ethanol. CLE was performed using the CellvizioLAB LSU F400 with Z ProFlex probe inserted i.g. and CLE images were monitored for 30 min before and after ethanol administration. Studies: 1) CLE imaging of gastric mucosa including epithelium and microvasculature; 2) vascular permeability; 3) mucosal blood flow dynamics; 4) progenitor cell integrity; 5) molecular imaging of VEGFR2 using labeled antibody; 6) detection of i.v. injected bone marrow-derived stem cells (BMDSC) in gastric mucosa. For comparison we performed quantitative histology, and transmission and scanning electron microscopy (EM). Results: At baseline, CLE of rat gastric mucosa demonstrated a normal gastric gland pattern, vasculature, continuous microvascular blood flow and low vascular permeability. Ethanol induced the exfoliation of surface epithelium within 2-3 min, followed by a 550% increase in vascular permeability (p<0.001) at 3-5 min; rupture of microvessels within 5-10 min, extensive extravasation of erythrocytes and vascular stasis. Progenitor cells were severely damaged. Histology and EM confirmed these changes. Pretreatment with HTL reduced ethanol-induced vascular permeability by 55% (p<0.01), preserved blood flow and reduced extent and severity of injury (all p<0.01). In control rats VEGFR2 was visualized in endothelial cells of blood vessels and i.v. injected BMDSC were present in gastric microcirculation. Conclusions: 1) CLE enables precise in vivo, real time analysis of events taking place during gastric mucosal injury and evaluation of mucosal protection. 2) Microvascular injury and increased vascular permeability occur early and precede progenitor cell damage and deep hemorrhagic necrosis. 3) CLE provides a significant advantage over standard histologic and EM assessment, by allowing real time monitoring of in vivo mucosal structure and function, e.g. vascular permeability, and in vivo molecular imaging.

Melatonin reduces inflammation and recovers endogenous ghrelin in acute necrotizing pancreatitis in rats

The present study aimed to evaluate the therapeutic effects of melatonin on either ghrelin secretion or gastric mucosal injury in acute necrotizing pancreatitis (ANP). ANP was induced in rats by L-arginine. Prior to L-arginine injection, the rats were pre-treated with melatonin for 30 min. Following the last injection, the animals were sacrificed at different time-points. The levels of ghrelin and melatonin in the serum and gastric tissue were detected by ELISA. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and malondialdehyde (MDA) as well as total superoxide dismutase (T-SOD) activities in gastric tissue were measured. In rats with ANP, acute gastric injury was observed, and the levels of MDA, SOD, TNF-α and IL-6 were significantly increased. The melatonin levels in serum or gastric tissue peaked at 6 h and returned to normal levels at 12 h after melatonin was administered. However, ghrelin remained at low levels during the first 12 h, but it recovered at 24 h and continued increasing, while the levels of oxidative stress damage and activity of inflammatory factors were decreased. The protective effects of melatonin on acute gastric injury during the early stages of ANP may be mediated through anti-oxidative and anti-inflammatory activities, while at advanced stages of ANP, it may be mediated through the recovered endogenous ghrelin.

Role of the nucleus tractus solitarii in the protection of pre-moxibustion on gastric mucosal lesions.

Previous studies have shown that somatic sensation by acupuncture and visceral nociceptive stimulation can converge in the nucleus tractus solitarii where neurons integrate signals impacting on the function of organs. To explore the role of the nucleus tractus solitarii in the protective mechanism of pre-moxibustion on gastric mucosa, nucleus tractus solitarii were damaged in rats and pre-moxibustion treatment at the Zusanli (ST36) point followed. The gastric mucosa was then damaged by the anhydrous ethanol lavage method. Morphological observations, enzyme linked immunosorbent assays, and western immunoblot analyses showed that gastric mucosa surface lesion and the infiltration of inflammatory cells were significantly ameliorated after pre-moxibustion treatment. Furthermore, the gastric mucosal damage index and somatostatin level were reduced, and epidermal growth factor content in the gastric mucosa and heat-shock protein-70 expression were increased. These results were reversed by damage to the nucleus tractus solitarii. These findings suggest that moxibustion pretreatment at the Zusanli point is protective against acute gastric mucosa injury, and nucleus tractus solitarii damage inhibits these responses. Therefore, the nucleus tractus solitarii may be an important area for regulating the signal transduction of the protective effect of pre-moxibustion on gastric mucosa.

Effects of glutathione on plasma heat shock protein 70 of acute gastric mucosal injury in rats exposed to positive acceleration

To explore the change of plasma heat shock protein 70 (HSP70) in rats exposed to acute gastric mucosal injury under the condition of positive acceleration (+Gz) and elucidate the effects of glutathione (GSH) and the corresponding protective mechanisms. A total of 40 male SD rats were randomly by computer randomization into 4 groups of ethanol control, +5 Gz value exposure, +10 Gz value exposure and GSH protection (n = 10 each). GSH protection group received adaptive feeding for 7 days and then an intraperitoneal injection of GSH for 3 consecutive days. All 4 groups fasted for 24 hours within 10 days, water deprivation for 12 hours and a gastric lavage of anhydrous ethanol (0.4 ml/100 g) for 1 hour, ethanol control group had no acceleration,+5 Gz value exposure group at + 5 Gz and the latter two groups respectively at +10 Gz for around 3 min.Each group underwent anesthesia of pentobarbital after centrifuge immediately. Abdominal aortic blood samples were collected and gastric tissues harvested for observation of mucosal injury. Mucosal damage index was calculated by the GUTH method. And the plasma content of HSP70 was measured by radioimmunoassay. (1) Gastric mucosa of each groups rats were injured. Damage was significantly reduced by GSH pretreatment, ethanol control group had less injury, the injury of +5 Gz value exposure group was aggravated compared with the control group (gastric mucosal injury index: 25.4 (14.0-30.0) vs 10.0 (9.2-13.9), P = 0.001); +10 Gz value exposure group mucosal injury was heaviest (47.2 (41.5-60.1)) . There were diffuse hyperemia, edema and erosion with a large area of bleeding spots and flat mucosal folds.It had statistically significant differences with the first two groups (all P < 0.01); GSH protection group was lightest at 9.5 (7.5-14.1). Compared with the +10 Gz value exposure group, mucosal damage was milder (P < 0.01).(2) The plasma levels of HSP70 of +5 Gz value exposure had no significant differences with the control and ethanol groups ((6.5 ± 0.5) ng/ml, P = 0.897); HSP70 plasma level ((5.9 ± 0.5) ng/ml) of +10 Gz value exposure was significantly lower than those of the first two groups (P = 0.018,0.014); GSH protection group ((7.0 ± 0.5) ng/ml) was significantly higher than the level of +10 Gz value exposure group (P < 0.01). +Gz exposure may cause the altered levels of plasma HSP70.High +Gz value exposure reduces its content and aggravates gastric mucosal injury. And glutathione reduces the injury of gastric mucosa through elevated plasma HSP70.

Banhabaekchulchunma-tang, a traditional herbal formula attenuates absolute ethanol-induced gastric injury by enhancing the antioxidant status

BackgroundBanhabaekchulchunma-tang (hange-byakujutsu-tenma-to in Japanese and banxia-baizhu-tianma-tang in Chinese) is a mixture of fourteen herbs. It is used traditionally for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of a Banhabaekchulchunma-tang water extract (BCT) against ethanol-induced acute gastric injury in rats.MethodsGastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the BCT group were given oral doses of omeprazole (50 mg/kg) or BCT (400 mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of BCT, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. In addition, we conducted an acute toxicity study to evaluate the safety of BCT according to OECD guideline.ResultsBCT reduced ethanol-induced hemorrhage, hyperemia, and loss of epithelial cell in the gastric mucosa. BCT reduced the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, and increased the mucosal GSH content and the activities of antioxidant enzymes. In addition, BCT did not cause any adverse effects at up to 5000 mg/kg.ConclusionsThese results indicate that BCT protects the gastric mucosa against ethanol-induced gastric injury by increasing the antioxidant status. We suggest that BCT could be developed as an effective drug for the treatment of gastric injury caused by alcohol intake.