Acute Gastric Damage Research Articles

Tricholoma matsutake heptapeptide prevents gastric mucosa injury by regulating oxidative stress‐related mitochondrial function and mucous layer integrity

AbstractShort‐term excessive alcohol consumption easily leads to ethanolic gastric injury. Recent research on bioactive functional factors in preventing and treating ethanol‐induced acute gastric injury has garnered attention. This study explored the direct protective effects of the Tricholoma matsutake‐derived peptide Ser–Ala–Pro–Trp–Gly–Leu–Ala (SAPWGLA) on ethanol‐induced acute gastric damage. The results showed that SAPWGLA showed dose‐dependent protection against gastric mucosal injury, including the regulation of oxidative stress and mitochondrial function, as well as the enhancement of mucosal barrier integrity. SAPWGLA maintained normal mitochondrial metabolism by alleviating intracellular reactive oxygen species (ROS) accumulation; 400 mg/mL SAPWGLA reduced ROS levels by 81.72 ± 1.55% and reversed the decrease of MMP by ethanol to 1.22 ± 0.01 (J‐aggregates/monomer) in GES‐1 cells. Also, SAPWGLA enhanced the tight junctions between GES‐1 cells. In addition, SAPWGLA improved the integrity of the mucosal barrier by maintaining the balance of the mucus layer and regulating the expression of TJ proteins. Daily oral administration of SAPWGLA (50 mg/kg) exhibited a restoration in hexosamine to 10.76 ± 0.73 mg/g prot, a regulation in claudin‐1, occludin, and ZO‐1 (1.21‐, 1.39‐, and 0.73‐fold of the control group). These findings suggest that SAPWGLA can be a potential novel therapeutic approach to dealing with acute gastric injury caused by ethanol.

Astrocytes in the spinal cord contributed to acute stress-induced gastric damage via the gap junction protein CX43

Rat restraint water-immersion stress (RWIS) is a compound stress of high intensity and is widely used to study the pathological mechanisms of stress gastric ulcers. The spinal cord, as a part of the central nervous system, plays a dominant role in the gastrointestinal tract, but whether the spinal cord is involved in rat restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of spinal astrocytic glial fibrillary acidic protein (GFAP), neuronal c-Fos, connexin 43 (Cx43), and p-ERK1/2 during RWIS by immunohistochemistry and Western blotting. In addition, we intrathecally injected the astrocytic toxin L-a-aminoadipate (L-AA), gap junction blocker carbenoxolone (CBX), and ERK1/2 signaling pathway inhibitor PD98059 to explore the role of astrocytes in the spinal cord in RWIS-induced gastric mucosal damage and its possible mechanism in rats. The results showed that the expression of GFAP, c-Fos, Cx43, and p-ERK1/2 was significantly elevated in the spinal cord after RWIS. Intrathecal injection of both the astrocyte toxin L-AA and the gap junction blocker CBX significantly attenuated RWIS-induced gastric mucosal damage and decreased the activation of astrocytes and neurons induced in the spinal cord. Meanwhile, the ERK1/2 signaling pathway inhibitor PD98059 significantly inhibited gastric mucosal damage, gastric motility and RWIS-induced activation of spinal cord neurons and astrocytes. These results suggest that spinal astrocytes may regulate the RWIS-induced activation of neurons via CX43 gap junctions and play a critical role in RWIS-induced gastric mucosa damage through the ERK1/2 signaling pathway.

Digestion Resistance of Soybean 7S Protein and Its Implications for Reinforcing the Gastric Mucus Barrier.

Previous studies have found that soybean protein, especially soybean 7S protein (β-conglycinin), exhibits digestion resistance, but the mechanism of digestion resistance and its implications for human health are still unclear. Here, we show that the extracted soybean 7S protein contains both oligomer globulins and amyloid aggregates, while the gastric digested soybean 7S protein only contains amyloid aggregates and thus exhibits digestion resistance. An animal experiment shows that un-digestible soybean 7S protein effectively prevents aspirin-induced acute gastric mucosa damage. The impacts of un-digestible soybean 7S protein on gastric mucus barrier properties are investigated using quartz crystal microbalance with dissipation (QCM-D), Langmuir monolayer, and multiple particle tracking (MPT). Results show that these un-digestible protein aggregates can penetrate into gastric mucus, increase the viscosity and compactness of the mucin layer, and reinforce the gastric mucus barrier properties. The findings are helpful to understand that high consumption of non-fermented soybean foods is associated with a decreased risk of gastric cancer.

Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption.

Pelubiprofen (PEL), which is a commercialized non-steroidal anti-inflammatory drug (NSAID), is associated with the risk of gastrointestinal (GI) adverse events following long-term exposure and has poor water-soluble properties. Here, a new pelubiprofen tromethamine (PEL-T) with improved solubility, permeability, GI safety, and absorption, compared to PEL, has been developed. The nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) results confirmed that the PEL-T was well formed. The powder of PEL-T showed the presence of additional 6H protons at δ 3.66–3.61 in the 1H NMR spectrum, and shifted the sharp endothermic peaks at 129 °C in DSC, and the spectrum of distinct absorption peaks in FT-IR. In addition, compared with PEL, PEL-T showed a significantly improved solubility in various media and an increased permeability coefficient (Kp) in Caco-2 cells. Furthermore, compared to PEL oral administration, PEL-T was found to significantly reduce the damaged area in an acute gastric damage rat model. The pharmacokinetic study of the PEL-T powder showed higher maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from 0 h to the last time point (AUCt) than those of the PEL powder. Taken together, our data suggest that PEL-T is a recommendable candidate with enhanced gastrointestinal safety and better absorption compared with commercial PEL.

Ethanolic extract of okra has a potential gastroprotective effect on acute gastric lesions in Sprague Dawley rats.

Okra (Abelmoschus esculentus) has various bioactive components used for the treatment of different diseases such as gastritis and ulcers. This research aims to examine the anti‐inflammatory and anti‐ulcer attributes of okra extract against gastric lesions. Adult Sprague Dawley male albino rats were divided into five groups. The negative control (G1) received normal feed, positive control (G2) received ulcer‐inducing drug aspirin 150 mg/kg of body weight (b.w), G3 group received reference drug omeprazole 20 mg/kg of b.w, G4 group received okra extract 250 mg/kg of b.w, and G5 group received 500 mg/kg of b.w. Acute gastric damage was induced in G1, G2, G3, and G4 using aspirin 150 mg/kg of b.w, during 14‐day‐long efficacy trials after that all the animals were sacrificed. Anti‐ulcer parameters and histopathological analysis of stomachs were performed to evaluate the degree of recovery against tissue damage by the administration of okra extract. The obtained results indicated that the 500 mg/kg of b.w okra extract exerted a protective effect in aspirin‐induced gastric ulcers by significantly (p < .05) reducing ulcer score, ulcer area, total acidity, and gastric volume, and significantly (p < .05) increasing gastric pH. Moreover, histopathological observation revealed that gastric mucosa was normal in G1, G3, G4, and G5; however, disruptions in the gastric epithelium were observed in G2. Congestion was observed in all groups except G1 and G5. Gastric pits and gastric glands were increased in size in G2 and G4. A higher concentration of okra extract (500 mg/kg of b.w) showed almost similar results when compared to the reference drug omeprazole.

Group 2 Innate Lymphoid Cells Coordinate Damage Response in the Stomach

Severe injury to the lining of the stomach leads to changes in the epithelium (reprogramming) that protect and promote repair of the tissue, including development of spasmolytic polypeptide-expressing metaplasia (SPEM) and tuft and foveolar cell hyperplasia. Acute gastric damage elicits a type-2 inflammatory response that includes production of type-2 cytokines and infiltration by eosinophils and alternatively activated macrophages. Stomachs of mice that lack interleukin 33 (IL33) or interleukin 13 (IL13) did not undergo epithelial reprogramming after drug-induced injury. We investigated the role of group 2 innate lymphoid cells (ILC2s) in gastric epithelial repair. Acute gastric injury was induced in C57BL/6J mice (wild-type and RAG1 knockout) by administration of L635. We isolated ILC2s by flow cytometry from stomachs of mice that were and were not given L635 and performed single-cell RNA sequencing. ILC2s were depleted from wild-type and RAG1-knockout mice by administration of anti-CD90.2. We assessed gastric cell lineages, markers of metaplasia, inflammation, and proliferation. Gastric tissue microarrays from patients with gastric adenocarcinoma were analyzed by immunostaining. There was a significant increase in the number of GATA3-positive ILC2s in stomach tissues from wild-type mice after L635-induced damage, but not in stomach tissues from IL33-knockout mice. We characterized a marker signature of gastric mucosal ILC2s and identified a transcription profile of metaplasia-associated ILC2s, which included changes in expression of Il5, Il13, Csf2, Pd1, and Ramp3; these changes were validated by quantitative polymerase chain reaction and immunocytochemistry. Depletion of ILC2s from mice blocked development of metaplasia after L635-induced injury in wild-type and RAG1-knockout mice and prevented foveolar and tuft cell hyperplasia and infiltration or activation of macrophages after injury. Numbers of ILC2s were increased in stomach tissues from patients with SPEM compared with patients with normal corpus mucosa. In analyses of stomach tissues from mice with gastric tissue damage and patients with SPEM, we found evidence of type 2 inflammation and increased numbers of ILC2s. Our results suggest that ILC2s coordinate the metaplastic response to severe gastric injury.

Effect of IS01957, a para-coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy.

Diclofenac is one of the world's largest selling nonsteroidal anti-inflammatory drugs. The major concerns related to oral diclofenac therapy are gastrointestinal and cardiovascular side effects for which explicitly emphasis has been given to use it at lowest effective dose for the shortest duration. On the other hand, IS01957 has been designed under the purview of anti-inflammatory drug and bioavailability enhancer. IS01957 have dual action on inflammation and nociception with acceptable safety profile. In the quest for a suitable combination with improved therapeutic efficacy and better tolerability, pharmacodynamic and pharmacokinetic interaction studies were performed for diclofenac with or without IS01957 in mice model. Results showed that IS01957 enhanced both anti-inflammatory effect and plasma concentration of diclofenac upon concomitant oral administration. These interesting results steered to enumerate the possible role of IS01957 towards diclofenac pharmacokinetics through a panel of mechanistic investigations: (a) BCRP dependent ATPase activity was markedly interfered by IS01957; (b) IS01957 increased the intestinal permeability of diclofenac in the single pass in-situ perfusion model; (c) IS01957 inhibited the CYP2C9 catalyzed diclofenac 4-hydroxylation in human liver microsomes. Immunoblotting results suggest that diclofenac action was improved significantly in the presence of IS01957 involving MAPK pathways. Finally acute gastric damage study showed that IS01957 in combination with diclofenac was better to improve the desired PGE2 level as compare to alone. In nutshell, IS01957 have potential to augment the efficacy of diclofenac through pharmacokinetic modulation. Further investigations are required for dose reduction of diclofenac to combat its liabilities before going into clinical setting.

Cystine/Glutamate Antiporter (xCT) Is Required for Chief Cell Plasticity After Gastric Injury.

Background & AimsMany differentiated epithelial cell types are able to reprogram in response to tissue damage. Although reprogramming represents an important physiological response to injury, the regulation of cellular plasticity is not well understood. Damage to the gastric epithelium initiates reprogramming of zymogenic chief cells into a metaplastic cell lineage known as spasmolytic polypeptide-expressing metaplasia (SPEM). The present study seeks to identify the role of xCT, a cystine/glutamate antiporter, in chief cell reprogramming after gastric injury. We hypothesize that xCT-dependent reactive oxygen species (ROS) detoxification is required for the reprogramming of chief cells into SPEM.MethodsSulfasalazine (an xCT inhibitor) and small interfering RNA knockdown were used to target xCT on metaplastic cells in vitro. Sulfasalazine-treated wild-type mice and xCT knockout mice were analyzed. L635 or DMP-777 treatment was used to chemically induce acute gastric damage. The anti-inflammatory metabolites of sulfasalazine (sulfapyridine and mesalazine) were used as controls. Normal gastric lineages, metaplastic markers, autophagy, proliferation, xCT activity, ROS, and apoptosis were assessed.ResultsxCT was up-regulated early as chief cells transitioned into SPEM. Inhibition of xCT or small interfering RNA knockdown blocked cystine uptake and decreased glutathione production by metaplastic cells and prevented ROS detoxification and proliferation. Moreover, xCT activity was required for chief cell reprogramming into SPEM after gastric injury in vivo. Chief cells from xCT-deficient mice showed decreased autophagy, mucus granule formation and proliferation, as well as increased levels of ROS and apoptosis compared with wild-type mice. On the other hand, the anti-inflammatory metabolites of sulfasalazine did not affect SPEM development.ConclusionsThe results presented here suggest that maintaining redox balance is crucial for progression through the reprogramming process and that xCT-mediated cystine uptake is required for chief cell plasticity and ROS detoxification.

Protective Effects of Dioscorea batatas Flesh and Peel Extracts against Ethanol-Induced Gastric Ulcer in Mice.

Gastric ulcer is a major digestive disorder and provoked by multifactorial etiologies, including excessive alcohol consumption. In this study, we examined the gastroprotective effect of aqueous and ethanolic extracts of Dioscorea batatas Decne (DBD; commonly called Chinese yam) flesh or peel against acidified ethanol-induced acute gastric damage in mice. Our findings demonstrated that oral supplementation of aqueous or ethanolic extracts of DBD flesh or peel before ulcer induction was significantly effective in macroscopically and histologically alleviating ethanol-induced pathological lesions in gastric mucosa, decreasing the plasma levels of inflammatory mediators, such as nitric oxide and interleukin-6, attenuating the gastric expression of cyclooxygenase-2, and increasing the gastric content of prostaglandin E2. In particular, pretreatment with the flesh extract prepared in 60% ethanol prominently decreased the expression of biomarkers of oxidative stress, including the plasma levels of 8-hydroxy-2-guanosine and malondialdehyde, and restored heme oxygenase-1 expression and superoxide dismutase activity in the stomach. Overall, these findings suggest that the oral supplementation with DBD extract, especially flesh ethanol extract, prior to excessive alcohol consumption, may exert a protective effect against ethanol-induced gastric mucosal damage in vivo, presumably through the activation of the antioxidant system and suppression of the inflammatory response.

Protective Effect of Ginger Extract against Aspirin Induced Acute Gastric, Renal and Hepatic Damage in Rats

Protective Effect of Ginger Extract against Aspirin Induced Acute Gastric, Renal and Hepatic Damage in Rats

Interaction between endogenous carbon monoxide and hydrogen sulfide in the mechanism of gastroprotection against acute aspirin-induced gastric damage

Acetylsalicylic acid (ASA) is mainly recognized as painkiller or anti-inflammatory drug. However, ASA causes serious side effects towards gastrointestinal (GI) tract which limits its usefulness. Carbon monoxide (CO) and hydrogen sulfide (H2S) have been described to act as important endogenous messengers and mediators of gastroprotection but whether they can interact in gastroprotection against acute ASA-induced gastric damage remains unknown.In this study male Wistar rats were pretreated with 1) vehicle (saline, i.g.), 2) tricarbonyldichlororuthenium (II) dimer (CORM-2, 5mg/kg i.g.), 3) sodium hydrosulfide (NaHS, 5mg/kg i.g.), 4) zinc protoporphyrin (ZnPP, 10mg/kg i.p.), 5) D,L-propargylglycine (PAG, 30mg/kg i.g.), 6) ZnPP combined with NaHS, 7) PAG combined with CORM-2 or 8) 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10mg/kg i.p.) combined with CORM-2 or NaHS and 30min later ASA was administered i.g. in a single dose of 125mg/kg. After 1h, gastric blood flow (GBF) was determined by H2 gas clearance technique and gastric lesions were assessed by planimetry and histology. CO content in gastric mucosa and COHb concentration in blood were determined by gas chromatography and H2S production was assessed in gastric mucosa using methylene blue method. Protein and/or mRNA expression for cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), heme oxygenase (HO)-1, HO-2, hypoxia inducible factor-alpha (HIF)-1α, nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-1 and COX-2, inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β were determined by Western blot or real-time PCR, respectively.ASA caused hemorrhagic gastric mucosal damage and significantly decreased GBF, H2S production, CO content, mRNA or protein expression for CSE, 3-MST, HO-2 and increased mRNA and/or protein expression for CBS, HO-1, Nrf-2, HIF-1α, iNOS, IL-1β, COX-2 in gastric mucosa and COHb concentration in blood. Pretreatment with CORM-2 or NaHS but not with PAG decreased ASA-damage and increased GBF. ZnPP reversed protective and hyperemic effect of NaHS but PAG failed to affect CORM-2-induced gastroprotection. CORM-2 elevated CO content, mRNA or protein expression for HO-1, Nrf-2, and decreased expression of CBS, HIF-1α, COX-2, IL-1β, iNOS, the H2S production in gastric mucosa and COHb concentration in blood. NaHS raised mRNA or protein expression for CSE, COX-1 and decreased mRNA expression for IL-1β and COHb level in blood.We conclude that CO is involved in gastroprotection induced by H2S while beneficial protective action of CO released from CORM-2 in gastric mucosa seems to be H2S-independent. In contrast to H2S, CO ameliorates hypoxia, regulates Nrf-2 expression but similarly to H2S acts on sGC-dependent manner to restore gastric microcirculation and exhibit anti-inflammatory activity in gastric mucosa compromised by ASA.

Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats.

Background/AimsThis study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-l-cysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats.MethodsSprague-Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanol-only group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor α, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed.ResultsPMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMK-S005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM.ConclusionsThese results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes.

Protective activity of salidroside against ethanol-induced gastric ulcer via the MAPK/NF-κB pathway in vivo and in vitro

Salidroside (Sal) is a traditional Chinese medicine with various pharmacological effects. The present study aimed to investigate the protective effect of Sal on ethanol-induced acute gastric ulcer and H2O2-induced gastric epithelial cell damage. 0.2ml ethanol and 400μM H2O2 were applied to establish a gastric ulcer model in vivo and in vitro respectively. The production of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α was analyzed, as well as myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD). MTT assay was used to detect cell viability. In addition, MAPK/NF-κB signal pathway-related proteins p-ERK, p-JNK, p-p38, p-IκBα and p-NF-κBp65 were analyzed to determine the underlying protective mechanism. Downstream genes such as cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and leukotrienes B4 (LTB4) were also measured. Obtained data indicated that Sal inhibited the overproduction of pro-inflammatory cytokines and enhanced antioxidant activity. Collectively, it is assumed that Sal could alleviate ethanol-induced acute gastric ulcer and H2O2-induced gastric epithelial cell damage through the MAPK/NF-κB pathway.

Protective effects of garlic extract, PMK-S005, against nonsteroidal anti-inflammatory drugs-induced acute gastric damage in rats.

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.

Gastroprotective Effect ofCochinchina momordicaSeed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

Background/AimsThe major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model.MethodsThe pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX.ResultsAll NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups.ConclusionsSK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Role of hydrogen sulfide in the physiology of gastrointestinal tract and in the mechanism of gastroprotection

Hydrogen sulfide (H2S) is commonly known as a toxic gas with an unpleasant odor. However, in the human body it plays a role as a gaseous transmitter involved in the control of physiological processes. Studies published so far have shown that H2S increased synaptic long-term potentiation in the central nervous system and exerted the inflammatory and anti-inflammatory effects on vascular endothelium. These effects clearly depend on the concentration of this gaseous molecule. H2S exerts vasodilatory effect in the cardiovascular system similar to those exhibited by carbon monoxide or nitric oxide. It is believed that H2S may play a potential role in the physiology of the gastrointestinal tract including the mechanism of gastroprotection of gastric mucosa and possibly exerts a protective effect in other parts of the digestive system. The administration of L-cysteine, the precursor of H2S or NaHS, the exogenous donor of this gaseous molecule, significantly reduced gastric damage induced by ethanol, an agent that is known to induce acute gastric damage and hemorrhagic necrosis to the gastric mucosa. The administration of H2S results in increased secretion of protective bicarbonate and mucus secretions and these effects could, in part, explain the H2S-induced protection of duodenal mucosa against the damage induced by gastric acid. Despite these promising results, little is known about the therapeutic efficacy of H2S in relation to two other important gases, nitric oxide and carbon monoxide, and future studies are definitely needed to assess its usefulness in the treatment of upper and lower gastrointestinal tract disorders.

Biological activities of Pseudevernia furfuracea (L.) Zopf extracts and isolation of the active compounds

Ethnopharmacological relevancePseudevernia furfuracea (L.) Zopf (Parmeliaceae) is a common epiphytic lichen in the conifer-hardwood forest of Anatolia. This species is used in traditional medicine in Turkey as a treatment for wounds, eczema and hemorrhoids. Aim of the studyThe present study was designed to investigate the active compounds from Pseudevernia. furfuracea, and the isolation studies yielded atraric acid (Aslan et al., 2006) as the major compound and a mixture of methyl hematommate (Baumann, 1960) and methyl chlorohematommate (Bayır et al., 2006). Furthermore, methanolic extract from thalli of Pseudevernia. furfuracea and its fractions and isolates (Aslan et al., 2006; Baumann, 1960; Bayır et al., 2006) were investigated for in vitro antimicrobial and antioxidant activities, and in vivo antinociceptive, anti-inflammatory and wound healing activities. Material and methodsAntimicrobial activities of the samples were determined by using the disc diffusion technique. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used as a rapid TLC screening method to evaluate the antioxidant activity of Pseudevernia. furfuracea. The thiobarbituric acid (TBA) test was used to assess the efficacy of the extracts in protecting liposomes from lipid peroxidation. In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. p-Benzoquinone-induced abdominal constriction test was used to explore the antinociceptive effects of the extracts. Moreover, the wound healing potential of the plant extracts that were evaluated by using in vivo incision and excision wound models on rats and mice, were comparatively assessed with a reference ointment Madecassol®. ResultsSignificant antimicrobial activities were observed against Gram (+) microorganisms and Candida krusei and Candida. dubliniensis in dichloromethane (DCM) and ethyl acetate (EtOAc) extracts and isolates. The methanol (MeOH), DCM and EtOAc extracts of the lichen were found to possess moderate inhibitory activity on lipid peroxidation. Methanolic extract of the lichen was found to possess significant inhibitory activity on the carrageenan-induced hind paw edema model in mice whereas the other fractions did not show any activity. While DCM and EtOAc extracts and fractions showed notable anti-inflammatory activity on carrageenan-induced hind paw edema model without inducing any apparent acute toxicity or gastric damage. Moreover, topical application of the ointment prepared with MeOH extract and EtOAc fraction onto the incised wounds exerted remarkable wound healing activity. ConclusionThe results of these experimental studies exhibited that nonpolar fractions of Pseudevernia. furfuracea have significant antimicrobial activity against especially Candida species and polar fractions (especially MeOH) display antioxidant, anti-inflammatory, antinociceptive and wound healing activities.

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

Background/AimsAging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages.MethodsFor the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours.ResultsThe gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05).ConclusionsNSAID-induced acute gastric damage increased in a dose- and age-dependent manner.

Does commercial aloe vera protects the structure of the gastric mucosa against acute nonsteroidal anti-inflammatory drug (diclofenac sodium)-induced damage?

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.

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Mucus is known to contribute significantly to the prevention and repair of mucosal damage throughout the gastrointestinal tract. Although not normally expressed in the stomach, mucin-2 (MUC-2, encoded by the MUC2 gene) is expressed in certain disease states. The aim of this study was to determine in a mouse model whether the absence of Muc-2 would result in impaired susceptibility to and healing of gastric mucosal injury. Acute gastric damage was induced in mice deficient in Muc-2 and in wild-type controls, through oral administration of indomethacin. Chronic gastric ulcers were induced by serosal application of acetic acid. The extent of injury and the extent of healing of the damage over time were examined in both models. Indomethacin administration caused similar levels of gastric damage in Muc-2-deficient and wild-type mice, but the erosions healed more slowly in the former. Acetic acid-induced gastric ulcers were initially similar in size in Muc-2-deficient and wild-type mice of both sexes, but ulcer healing was significantly impaired in male Muc-2-deficient mice. Induction of cyclooxygenase-2 in the stomach, in response to indomethacin- or acetic acid-induced ulceration, was significantly reduced in male Muc-2-deficient mice. This phenomenon, and the sex specificity, was also apparent in bone marrow-derived macrophages stimulated with endotoxin. These results demonstrate a marked impairment of gastric mucosal repair in male Muc-2-deficient mice that may be related to an insufficient induction of cyclooxygenase-2, an enzyme known to contribute to mucosal repair.