Oxidative Stress In Gastric Mucosa Research Articles

Composition and Anti-ulcer Activity of the Essential Oil from Citri Reticulatae Pericarpium in Rodents

HIGHLIGHTS The major components of the essential oil of Citri Reticulatae Pericarpium (EOC) are d-limonene (92.3%) and β-Myrcene (1.3%). EOC protects against gastric mucosal lesions induced by HCl/EtOH and indomethacin. EOC heals acetic acid-induced gastric ulcer. EOC preserves antioxidant enzyme and reduces oxidative stress in gastric mucosa.

Antioxidant defense of fish collagen peptides attenuates oxidative stress in gastric mucosa of experimentally ulcer-induced rats.

The aim of the present study was to investigate the ability of fish collagen peptides (FCP) from the skin of great hammerhead shark (Sphyrna mokarran) to avert the occurrence of gastric ulcer in experimental rats. FCP treatment prevented the formation of ulcerative lesions on gastric tissues with 86% of inhibition. The histopathology analysis of gastric tissue revealed that the FCP intake prevented the occurrence of hemorrhage and erosion in gastric tissue with formation of mild edema and necrosis, as well as normalized the pH and volume of gastric juice. It also downregulated the expression of pro-inflammatory marker interferon-ɤ (IFN-ɤ) and upregulated the anti-inflammatory marker interleukin-4 (IL-4) in gastric tissue. FCP is capable to modulate the oxidative stress by enhancing the activity of antioxidant defense enzymes superoxide dismutase (SOD) and catalase and by lowering the levels of membrane lipid peroxidation.

Modulation of gastric acid secretion by cannabinoids in rats.

The current study aimed to evaluate the role of cannabinoid receptors in the regulation of gastric acid secretion and oxidative stress in gastric mucosa. To fulfill this aim, gastric acid secretion stimulated with histamine (5 mg/kg, subcutaneous [SC]), 2-deoxy- d-glucose (D-G) (200 mg/kg, intravenous) or -carbachol (4 μg/kg, SC) in the 4-hour pylorus-ligated rats. The CB1R agonist ( N-arachidonoyl dopamine, 1 mg/kg, SC) inhibited gastric acid secretion stimulated by D-G and carbachol but not in histamine, reduced pepsin content, and increased mucin secretion. Furthermore, it decreased malondialdehyde (MDA) and nitric oxide (NO) contents with an increase in glutathione (GSH) and paraoxonase 1 (PON-1). Meanwhile, CB2R antagonist (AM630, 1 mg/kg, SC) inhibited gastric acid secretion stimulated by D-G and reduced MDA and NO contents with an increase in GSH and PON-1. Meanwhile, CB1R antagonist rimonabant or CB2R agonist GW 405833 had no effect on stimulated gastric acid secretion. Therefore, both CB1R agonist and CB2R antagonist may exert antisecretory and antioxidant potential in the stomach.

ATB 340, МОДУЛЯТОР АКТИВНОСТІ СУЛЬФІТ ОКСИДАЗИ, ЗМЕНШУЄ ОКИСНИЙ СТРЕС У СЛИЗОВІЙ ОБОЛОНЦІ ШЛУНКА СТАРИХ ЩУРІВ ЗА УМОВ ГІПЕРГЛІКЕМІЇ ТА СТРЕСУ

Introduction. Sulfite oxidase (SO) is one of mitochondrial enzymes involved in H2S-pathway and multiple physiological processes, including oxidative stress. The dominant sulfide oxidation products vary in a tissue-specific manner, whatever SO/oxidative stress involved in gastric mucosa (GM) injury is unclear. Our labs has shown potent cytoprotective and anti-inflammatory effects of H2S-rich compounds, including hybrid nonsteroidal anti-inflammatory drugs (H2S-NSAIDs) but their effects on age-related metabolic dysfunction in GM exposed to long-term postprandial hyperglycemia by high fructose diet (HFD) is still unknown. Aim. To characterize the activity of sulfite oxidase (SO) and role of oxidative stress in older rats GM exposed to HFD and to assess the therapeutic effect of the recently synthesized H2S donor, hybrid NSAID, H2S-acetylsalicylic acid (H2S-ASA, ATB 340) on adult vs old rat GM. Material and methods. Adult (n=24) and old (n=43) were divided to control groups with standard diet (SD) and 28-days hypercaloric high-fructose diet (HFD, V. Kozar, 2008) without and with water-immersion stress (WIS) induction (Takagi, 1964). HFD groups on 19-28 day were supplemented per os: a) vehicle (1.0 ml of saline per os),; b) NaHS, 100 μmol/kg/day; c) vehicle and stress induction; d) NaHS, 100 μmol/kg/day and stress induction; e) ASA, 10 mg/kg/day and stress induction; f) conventional aspirin (ASA), 10 mg/kg/day and NaHS, 100 μmol/kg/day and stress induction; g) ATB-340, 17.5 mg/kg/day and stress induction. The integrity of the GM was analyzed by histological scoring based on studies of GM samples. Indicator of oxidative stress, malonic dialdehyde (MDA) and activity of SO in GM were estimated by standard biochemical methods. Results. We have observed a different SO expression in GM in adult vs old rats with SD and HFD without and with WIS. The effect of HFD resulted in an increase in SO activity in old rats by 15%, whereas in adults by 14%. MDA content changes were similar. In animals that were administered NaHS, adult vs old MDA changes had a similar tendency, while SO activity in older rats was higher in 23%. The stress induction reduced SO activity in old animals by 35%, while in adult ones – by 22%, and the difference in the content of MDA reached 41%. The effect of exogenous NaHS in old rats under stress was highest when combined with ASA, while the MDA content was highest when classical aspirin was used, which coincided with similar changes in HS. Conclusion. Sulfite oxidase is the essential contributor to age-related oxidative stress in GM that was tested. Supplementation of ATB-340 (H2S-aspirin), which increases the H2S content in the tissues, reduces the symptoms of GM damage associated with a decrease in the activity of SO and the content of MDA, indicating the alleviation of oxidative stress, showing an anti-radical and anti-oxidant effects.

Amaranth oil reduces accumulation of 4-hydroxynonenal-histidine adducts in gastric mucosa and improves heart rate variability in duodenal peptic ulcer patients undergoing Helicobacter pylori eradication

Helicobacter pylori-induced oxidative stress in gastric mucosa (GM) is a milieu for the development of chronic gastritis, duodenal peptic ulcer (DPU), gastric cancer, and a number of extragastric diseases. Because our previous study revealed the accumulation of the protein adducts of lipid peroxidation product 4-hydroxynonenal (HNE) in GM, which persists after eradication of H. pylori, the aim of the study was to test whether Amaranth oil supplementation in addition to standard anti-Helicobacter treatment could prevent such accumulation of HNE in GM in H. pylori-positive DPU patients. Seventy-five patients were randomly split into two groups: group 1 – standard treatment (n = 39) and group 2 – standard treatment with additional supplementation of 1 ml of concentrated oil from amaranth seeds (Amaranthus cruenthus L., n = 36). Clinical analysis, including endoscopy with biopsies from antrum and corpus of the stomach were performed before and after the treatment, as was heart rate variability (HRV) recorded, as parameter of systemic, extragastric pathophysiological alterations in DPU patients. Improvement of clinical, endoscopic and histologic manifestations, and successful ulcer healing were observed in both the groups. Moreover, supplementation of amaranth oil in addition to standard anti-H. pylori treatment significantly reduced accumulation of HNE-histidine adducts in GM and increased HRV in DPU patients (p < .05). Therefore, standard treatments of DPU require additional therapeutic approaches, in accordance with integrative medicine principles, aiming to reduce persistence of oxidative stress, as was successfully done in our study by the use of amaranth oil.

Involvement of MAPK/NF-κB signal transduction pathways: Camellia japonica mitigates inflammation and gastric ulcer

Gastric ulcer is an important risk factor for human health globally. Camellia japonica (CJ) is a plant of which the fruits are used as traditional phytomedicine for inflammatory and immunomodulatory diseases; however, the underlying molecular mechanism has not been clarified. The present study aimed to investigate the immunopharmacological activities of Camellia japonica and validate its pharmacological targets. To evaluate the protective roles of Camellia japonica on LPS-induced inflammation in RAW 264.7 cells and HCl/EtOH-induced gastric ulcer in mice; we applied 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot analyses. We also determined the total phenolic and flavonoid content of Camellia japonica which might possess antioxidant and anti-inflammatory properties. We found the production of NO and ROS in RAW 246.7 cells were both suppressed by Camellia japonica. Moreover, Camellia japonica mitigated the HCl/EtOH-induced oxidative stress in gastric mucosa via the reduction of lipid peroxidation and elevation of NO production. Gastric mucosal damages were prominently improved by Camellia japonica, as confirmed by the histopathological evaluation. The gene expression of inflammatory cytokines and enzymes TNF-α, IL-6, IL-1β, iNOS, and COX-2 was notably downregulated by Camellia japonica. In addition, Camellia japonica markedly attenuated the MAPKs (ERK1/2, JNK, and p38) phosphorylation, COX-2 expression, and activation of transcription factor NF-κB and as well as phosphorylation and degradation of IκBα in gastric mucosa. Taken together, the intimated anti-inflammatory and gastroprotective mechanism of Camellia japonica is mediated by modulation of oxidative stress, inflammatory cytokines, and enzymes via suppression of MAPK/NF-κB signaling pathways.

Extrusion process of Acanthopanax senticosus leaves enhances the gastroprotective effect of compound 48/80 on acute gastric mucosal lesion in rats

ObjectiveTo investigate the gastroprotective effects of Acanthopanax senticosus leaves (ASLs) extrusion on acute gastric mucosal lesion in rats induced by compound 48 / 80 (C48 / 80). MethodsRats were divided into six groups: normal; C48/80-induced gastric lesion control; gastric lesion positive control (famotidine 4 mg/kg); gastric lesion administered with two levels of extruded ASLs (ASLE, 40 and 200 mg/kg); and gastric lesion treated with ASLs (ASL 200 mg/kg). Mucus secretion / damage was determined by immunohistological staining. Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression. Gastric mucosal oxidative-stress-related enzymes and malondialdehyde were determined. ResultsC48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs. The increased serum serotonin and histamine concentrations in C48/80-treated rats were also attenuated by ASLs. Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment, and ASLs ameliorated Bax and Bcl-2 expression. The extrusion process significantly augmented the effects of ASLs in a dose-dependent manner. ASLEs at 200 mg/kg normalized mucus damage / secretion, C48 / 80-induced increases of mucosal myeloperoxidase activity (index of inflammation), xanthine oxidase, and malondialdehyde content (index of lipid peroxidation). The effects of ASLs on Bax and Bcl-2 expression were also enhanced by extrusion. Furthermore, these effects of ASLEs at 200 mg/kg were similar to those of famotidine, a histamine H2-receptor antagonist commonly used to treat gastric ulcers. ConclusionASLEs prevented acute gastric mucosal lesion progression induced by C48/80, possibly by inducing mucus production, and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism.

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.

Oxidative stress and digestive diseasesEdited by Toshikazu Yoshikawa. 182 pp. $128.75. S. Karger Publishers, Inc., Basel, UK, 2001. ISBN 3-8055-7230-1. Web address for ordering: www.karger.com

It has become increasingly clear that oxidative stress, an imbalance between prooxidants and antioxidants, favoring the former, may play a role in initiating and mediating many diseases of the gastrointestinal tract. This book is a summary of papers given at the Symposium on Free Radicals in Digestive Diseases held in Kyoto, Japan, on October 20, 2000. The stated goal of this symposium and this book was to present “an in-depth and integrated account of the field of oxidative stress and digestive diseases.” It was therefore with great enthusiasm that this reviewer started reading this book, as a general review on this topic would be timely and a welcomed addition to the literature. It is unfortunate to state that these very broad goals of this book were not met. The book comprises 15 chapters and is organized into sections addressing general responses oxidative stress, neutrophil activation, oxidative stress in gastric mucosa, intestinal mucosa, and the hepatobiliary system, nitric oxide, and chemoprevention by antioxidants. About one-third of the chapters serve as general reviews on the topic, with the remaining articles summarizing specific experimental projects presented at the meeting. Some of the more general reviews on the issues are informative and broad, especially the series of chapters on neutrophils and their involvement in oxidative stress and diseases of the GI tract. The interest in the remaining chapters is rather “hit-or-miss” due to the specific nature of the projects being summarized. Furthermore, no attempt was made to standardize length, content, or presentation style between the chapters. The figures of one chapter in particular appear to be simple reproductions of presentation slides. In general though, the research articles are of interest to those involved in the field. Bottom Line: Although it does possess some good general reviews on the role of oxidative stress in GI diseases, this book serves mostly its original purpose, which is to summarize the proceedings of a meeting. The utility of this book as a general reference or review to the GI community as a whole is not very high.

Activation of MAPK (ERK2) by oxidative stress in gastric mucosa of portal hypertensive rats

Activation of MAPK (ERK2) by oxidative stress in gastric mucosa of portal hypertensive rats

Role of endogenous nitric oxide in ischaemia-reperfusion injury of rat gastric mucosa.

It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia-reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, NG-nitro-L-arginine or NG-monomethyl-L-arginine. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51chromium]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [51Cr]-EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L-arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia-reperfusion stress in rat gastric mucosa.

Protective Effect of Rebamipide against Hydrogen Peroxide-Induced Hemorrhagic Mucosal Lesions in Rat Stomach

Intragastric administration of 6% H2O2 induces gastric mucosal hemorrhagic lesions in rats. Intraperitoneal administration of rebamipide at 10 to 100 mg/kg dose-dependently prevented the H2O2-induced mucosal lesions. The fact that cimetidine, ranitidine and omeprazole could not prevent the gastric mucosa from developing H2O2-induced lesions indicates that acid secretion might not be the main cause of these lesions. The protective effect of rebamipide was partially reduced by indomethacin and completely blocked by diethyl maleate, a glutathione depressor. Gastric mucosal glutathione level and glutathione peroxidase and superoxide dismutase (SOD) activities were significantly decreased by 6% H2O2 instillation. Rebamipide at 100 mg/kg significantly inhibited the decreases in gastric mucosal glutathione level and SOD activity. These results suggest that H2O2-induced gastric mucosal lesions might partially involve a decrease in defense activities against reactive oxygen species and that the protective effect of rebamipide might be related to its ability to improve oxidative stress in gastric mucosa.