Oxidative Damage Of Gastric Mucosa Research Articles

Novel Carbon Dots Derived from Glycyrrhizae Radix et Rhizoma and Their Anti-Gastric Ulcer Effect

Glycyrrhizae Radix et Rhizoma (GRR) is one of the commonly used traditional Chinese medicines in clinical practice, which has been applied to treat digestive system diseases for hundreds of years. GRR is preferred for anti-gastric ulcer, however, the main active compounds are still unknown. In this study, GRR was used as precursor to synthesize carbon dots (CDs) by a environment-friendly one-step pyrolysis process. GRR-CDs were characterized by using transmission electron microscopy, high-resolution TEM, fourier transform infrared, ultraviolet-visible and fluorescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. In addition, cellular toxicity of GRR-CDs was studied by using CCK-8 in RAW264.7 cells, and the anti-gastric ulcer activity was evaluated and confirmed using mice model of acute alcoholic gastric ulcer. The experiment confirmed that GRR-CDs were the spherical structure with a large number of active groups on the surface and their particle size ranged from 2 to 10 nm. GRR-CDs had no toxicity to RAW264.7 cells at concentration of 19.5 to 5000 μg/mL and could reduce the oxidative damage of gastric mucosa and tissues caused by alcohol, as demonstrated by restoring expression of malondialdehyde, superoxide dismutase and nitric oxide in serum and tissue of mice. The results indicated the explicit anti-ulcer activity of GRR-CDs, which provided a new insights for the research on effective material basis of GRR.

Evaluation of Antiulcerogenic Activity of Clerodendron Infortunatum Extract on Albino Rat Gastric Ulceration

Clerodendron infortunatum Linn. (Verbenaceae) is an important and widely used medicinal plant, reported to contain active bitter substance like clerodin, has been widely used as tonic and anthelmintic agent in the country sides of North India. Though, variously used in Ayurveda, Unani system of medicine and Homeopathy in case of ailments like diarrhoea, skin disorders, venereal and scrofulous complaints, wounds, post-natal complications, as vermifuge, laxative and cholagogue, for the removal of ascarids in anus, as external applications on tumours, etc.,
 Background: The present study reports the antiulcer properties of 50% ethanolic extract of Clerodendron infortunatum Linn. (Verbenaceae) leaves have assessed in different acute and chronic gastric ulcer models in rats.
 Methods: EECI (100, 200 and 400 mg/kg body weight) was administered orally, twice daily for 5 days for prevention from ethanol (EtOH), Cold-restraint stress (CRS), Pylorus-ligation (PL) and 10 days for prevention of acetic acid induced ulcers.
 Results: The EECI showed significant gastric ulcer protective effect in doses of 400 mg/kg, when given twice daily for 5 days against gastric ulcers induced by ethanol (EtOH), cold restraint stress (CRS) and pyloric ligation (PL). EECI showed dose dependent decrease in ulcer index (UI) against ulcers induced by: (i) Ethanol (control UI: 29.52±2.4 mm2/rat, EECI decrease 21.12±2.3 – 5.3±1.0 (ii) Cold restraint stress (CRS) (control UI: 32.13±2.1, EECI decrease 24.02±2.2 – 4.7±1.1 (iii) pylorus ligation (control UI: 29.25±2.4 mm2/rat, EECI decrease 22.32±2.7 – 5.3±1.0, EECI 400 mg/kg significantly healed ulcers induced by 50% acetic acid after 5 (control UI: 32.30 ± 2.9, EECI decrease 26.27±1.9 – 8.56±0.98 and after 10 days treatment (control UI: 29.02 ± 2.6, healing 21.28±2.1 – 5.78±1.2. EECI prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by significant decrease in superoxide dismutase, and increase in catalase activity.
 Conclusions: Our results show that Clerodendron infortunatum Linn. (Verbenaceae) possess significant gastro-protective activity which might be due to gastric defence factors and clerodin might be the main constituents responsible for this activity.

HEME OXYGENASE-1 UPREGULATED BY MELATONIN: POTENTIAL PROTECTION AGAINST BURN-INDUCED OXIDATIVE GASTRIC MUCOSAL INJURY

SUMMARY Melatonin is indoleamine hormone derived from Ltryptophan. Due to its lipophilic nature, it is accessible to every cell. Melatonin has immunomodulatory and antioxidant activities thus protecting tissue injury. Heat shock proteins such as HSP32 known as heme oxygenase-1 (HO-1) possesses antioxidant, anti-inflammatory, and vasodilatory properties and plays an important role in the protecting of tissues from several stresses. The aim of study is to investigate the expression of HO-1 in gastric mucosa and its connection with oxidative stress and melatonin mediated protection after thermal injury. On rats back, under anesthesia, third degree burn was applied involving 30% of total body surface area (TBSA). Melatonin (10 mg per kg body mass) was injected i.p. immediately and 12 hours after thermal skin injury. We used tissue malondialdehyde (MDA), lipid peroxidation product, as a marker of oxidative stress. Gastric mucosa histopathology were observed on light microscopy and light immunohistochemistry investigating the HO-1 too. Results: The levels of MDA in gastric mucosa were elevated (p< 0.05). The HO-1 expression was significantly increased in rats with trauma. Melatonin inhibited elevation in lipid peroxidation product and augmented the increase in expression of HO-1 in the gastric mucosa. In conclusion, our data suggest that HO-1 induction following burn injury is an adaptive response protecting gastric mucosal against further oxidative damage. Melatonin increased the antioxidant capacity and restricted burn-induced oxidative damage in gastric mucosa and thus could be used therapeutically in organ protection.

Protective effect of standardized extract of Cleome viscosa against experimentally induced gastric lesions in the rat

Context: Cleome viscosa Linn. (Capparidaceae) is used traditionally in the Indian system of medicine as a carminative, anthelmintic, and diuretic, and used for healing wounds, ulcers and diarrhea.Objective: A 70% ethanol (EtOH) extract of the aerial parts of Cleome viscosa extract (CVE) was investigated for gastroprotective activity in different gastric ulcer models in order to validate ethnobotanical claims regarding the plant use in ulcers.Materials and methods: CVE (100, 200 and 400 mg/kg body weight) was administered orally, twice daily for 5 d, for prevention from EtOH, pylorus ligation (PL) and cold restraint stress (CRS)-induced ulcers in rats. Estimation of H+K+ATPase activity and gastric wall mucous were performed in EtOH-induced ulcer, antioxidant enzyme activities in supernatant mitochondrial fraction of CRS-induced ulcer, and gastric secretion parameters were estimated in PL-induced ulcer modelResults: CVE showed significant (p < 0.01) dose-dependent inhibition of lesion index in EtOH 15.93–42.30%, PL 26.34–59.28% and CRS 22.58–54.03%, respectively. CVE prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by a significant (p < 0.001) decrease in superoxide dismutase, and an increase in catalase activity. A significant (p < 0.01) decrease occurred in the level of H+K+ATPase, volume of gastric juice and total acidity. Simultaneously, the level of gastric wall mucus and pH were increased significantly (p < 0.05). High performance thin layer chromatography analysis showed the presence of quercetin and gallic acid (0.3% and 0.25% w/w, respectively) in CVE.Conclusions: Results of our study showed that C. viscosa possesses significant gastroprotective activity, probably due to free radical scavenging activity, and validates the folklore claim.

Thymohexin exhibits cytoprotective effect in experimental gastric lesions in rats both through the inhibition of inducible nitric oxide synthase and reduction of oxidative mucosal damage

Background and objectiveSome short peptides have recently been reported to exhibit gastroprotective properties but the role of NO-synthase system in these mechanisms still leaves much to be elucidated. That is why the purpose of our study was to explore the gastroprotective effect of the hexapeptide Arg–α-Asp–Lys–Val–Tyr–Arg (thymohexin) under conditions of the modeling of iNOS activity. Materials and methodsThe studies were performed on 80 outbred male rats. Gastric lesions were induced with epinephrine (2mg/kg) or indomethacin (30mg/kg). Fifteen minutes before the exposure to ulcerogens rats were pretreated with thymohexin alone and combined with l-arginine or aminoguanidine. Twenty-four hours later gastric mucosa damage, l-arginine/NOS/NO system, processes of lipoperoxidation, superoxide dismutase and catalase activity were assessed. ResultsThymohexin markedly attenuated both epinephrine- and indomethacin-induced gastric ulceration in rats, decreasing the area and score of mucosal lesions (p<0.05), iNOS activity (p<0.05) and malonic dialdehyde content (p<0.05) in gastric mucosa. The cytoprotective effect of thymohexin was significantly enhanced by l-arginine and aminoguanidine. The combination of thymohexin and l-arginine was superior to that with aminoguanidine. ConclusionsThymohexin protects gastric mucosa against epinephrine- and indomethacin-induced gastric lesions in rats. Thymohexin-induced gastroprotection is probably mediated by inhibition of iNOS and decrease of the oxidative damage in gastric mucosa.

Gastroprotective effect of standardized extract of Ficus glomerata fruit on experimental gastric ulcers in rats

Ethnopharmacological relevance Traditionally fruits of Ficus glomerata Roxb (Family: Moraceae) are used to treat anemia and gastrointestinal disorders. Aim Gastroprotective effect of 50% ethanolic extract of F. glomerata fruit (FGE) was studied in different gastric ulcer models in rats. Methods FGE (50, 100 and 200 mg/kg body weight) was administered orally, twice daily for 5 days for prevention from pylorus ligation (PL), ethanol (EtOH) and cold restraint stress (CRS) – induced ulcers. Estimation of H +K +ATPase activity and gastric wall mucous were performed in EtOH-induced ulcer and antioxidant enzyme activities in supernatant mitochondrial fraction of CRS-induced ulcers. Results FGE showed dose dependent inhibition of ulcer index in pylorus ligation, ethanol and cold restraint stress – induced ulcers. FGE prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by significant decrease in superoxide dismutase, H +K +ATPase and increase in catalase activity. High performance thin layer chromatography (HPTLC) analysis showed the presence of 0.57% and 0.36% w/w of gallic acid and ellagic acid in FGE. Conclusions Our results show that F. glomerata possess significant gastroprotective activity which might be due to gastric defence factors and phenolics might be the main constituents responsible for this activity.

Critical role of an endogenous gastric peroxidase in controlling oxidative damage in H. pylori-mediated and nonmediated gastric ulcer

The objective of the present study is to delineate the mechanism of oxidative damage in human gastric ulcerated mucosa despite the presence of some antioxidant enzymes. We report for the first time the critical role of an endogenous peroxidase, a major H 2O 2 metabolizing enzyme, in controlling oxidative damage in gastric mucosa. Human gastric mucosa contains a highly active peroxidase in addition to the myeloperoxidase contributed by neutrophil. In both non- Helicobacter pylori ( H. pylori)- and H. pylori-mediated gastric ulcer, when myeloperoxidase level increases due to neutrophil accumulation, gastric peroxidase (GPO) level decreases significantly. Moreover, gastric ulcer is associated with oxidative damage of the mucosa as evidenced by significant increase in lipid peroxidation, protein oxidation, and thiol depletion indicating accumulation of reactive oxygen metabolites (ROM). Mucosal total superoxide dismutase (Mn and Cu-Zn SOD) level also decreases significantly leading to increased accumulation of O 2 •−. To investigate the plausible ROM-mediated inactivation of the GPO during ulceration, the enzyme was partially purified from the mucosa. When exposed to an in vitro ROM generating system, using Cu 2+, ascorbate, and H 2O 2, the enzyme gets inactivated, which is dependent on Cu 2+, ascorbate, or H 2O 2. Insensitivity to SOD excludes inactivation by O 2 •−. However, complete protection by catalase indicates that H 2O 2 is essential for inactivation. Sensitivity to EDTA and hydroxyl radical ( OH) scavengers indicates that GPO is inactivated most probably by OH generated from H 2O 2. We propose that GPO is inactivated in vivo by ROM generated by activated neutrophil. This leads to further accumulation of endogenous H 2O 2 to cause more oxidative damage to aggravate the ulcer.

Role of Nitric Oxide and Mucus in Ischemia/Reperfusion-Induced Gastric Mucosal Injury in Rats

The present study aims at investigating the role of nitric oxide (NO) on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion (I/R) and its relation to mucus. NO synthesis modulators such as L-arginine and N^G-nitro-L-arginine methyl ester (L-NAME) were injected intraperitoneally to the rats 30 min prior to I/R which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. As a result, I/R increased lipid peroxide production and decreased the contents of glutathione (GSH), cGMP and mucus as well as GSH peroxidase activities of gastric mucosa. I/R decreased the activity and protein of NO synthase (NOS) in gastric mucosa. Pretreatment of L-arginine, a substrate for NOS, prevented I/R-induced alterations of gastric mucosa. However, L-NAME, an NOS inhibitor, deteriorated oxidative damage induced by I/R. In conclusion, NO has an antioxidant defensive role on gastric mucosa by maintaining mucus, GSH and GSH peroxidase, which were related to preservation of cGMP and NOS in gastric mucosa.

Lansoprazole enhances prostaglandin production and reduces cell oxidative damage in gastric mucosa

Lansoprazole enhances prostaglandin production and reduces cell oxidative damage in gastric mucosa

Effect of 16.16 Dimethyl Prostaglandin E&lt;sub&gt;2&lt;/sub&gt;, N-Acetyl-Cysteine and the Proton Pump Inhibitor BY 831–78 on Hydrogen Peroxide-Induced Mucosal Damage in the Rat Stomach

Reactive oxygen species are noxious to gastrointestinal mucosa and contribute to a variety of gastrointestinal diseases. We examined whether 16.16 dimethyl prostaglandin E2 (PG) is protective against the oxidizing action of 6% H2O2 causing gross hemorrhagic lesions in rat gastric mucosa. Male Wistar rats were treated with PG, 0.005-5 micrograms/kg, either intragastrically (i.g.) or subcutaneously, 30 min prior to i.g. administration of 6% H2O2, 0.5 ml/100 g. Further animals received 25 mg of the mucus dissolvent N-acetyl-cystein (NAC) following oral PG treatment or 30 mumol/kg of the H+K(+)-ATPase inhibitor BY 831-78 (BY), 4 h before onset of the experiments. Volume, pH and beta-N-acetyl-glucosaminidase and lactate dehydrogenase as parameters of cell damage were determined in the gastric juice. i.g. PG treatment achieved 60 and 55% reduction of the mucosal lesions in doses between 5 and 0.05 micrograms/kg, respectively. i.p. PG administration was effective in all doses tested. Gastric juice volume was only slightly and enzymes were not significantly affected by PG treatment. NAC did not diminish PG efficacy or aggravate mucosal lesions. Gastric acid suppression did not increase PG-induced protection but was strongly protective by itself, reducing damage by 75%. Low-dose PG treatment achieves an effective protection against oxidative damage in gastric mucosa, which is not the result of dilution or enhanced mucus production.