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Gastric Injury (gastric + injury)
Selected AbstractsMELATONIN PROTECTS AGAINST HYDROGEN PEROXIDE-INDUCED GASTRIC INJURY IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009Ahmed M Mohamadin SUMMARY 1Melatonin (MT) is a pineal hormone that is also abundant in the gut and has a well known role in scavenging oxygen free radicals. The aim of the present study was to evaluate the potential protective effects of MT against H2O2 -induced gastric lesions in rats. 2An experimental model of gastric ulceration was established in rats using 15% H2O2. Melatonin (12.5, 25 or 50 mg/kg, intagastrically) was administered to rats 30 min before H2O2 challenge. 3Intragastric administration of H2O2 resulted in haemorrhagic lesions in the fundic area of the stomach. Furthermore, H2O2 induced gastric oxidative stress, as indicated by depletion of reduced glutathione (GSH), inhibition of glutathione peroxidase (GPx) activity and elevation of malonedialdehyde (MDA) levels. These effects were accompanied by decreased gastric tissue levels of prostaglandin (PG) E2 and nitric oxide (NO), as well as increased levels of tumour necrosis factor (TNF)-,. Administration of MT (12.5, 25 or 50 mg/kg) 30 min before H2O2 significantly attenuated the development of gastric lesions in a dose-dependent manner. The protective effects of MT were accompanied by significant inhibition of the H2O2 -induced reduction in gastric content of GSH and GPx activity and elevation in MDA levels. Furthermore, MT antagonized H2O2 -induced reduction of gastric PGE2 and NO levels and elevation of TNF-,. 4In conclusion, MT protects rat gastric mucosa against H2O2 -induced damage. The observed protective effects of MT can be attributed, at least in part, to its anti-oxidant properties, preservation of PGE2 and NO levels, as well as inhibition of TNF-, induction in gastric tissues. [source] Nerve growth factor and gastric hyperalgesia in the ratNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2003K. Lamb Abstract We recently demonstrated an association between the development of hyperalgesia and an increase in nerve growth factor (NGF) during gastric inflammation. We hypothesized that block of NGF signalling will blunt injury-induced hyperalgesia. Male Sprague,Dawley rats (300,400 g) were anaesthetized, the stomach was exposed and placed in a circular clamp. Acetic acid (60%) or saline (control) was injected into this area and aspirated 45 s later, resulting in kissing ulcers. A balloon was surgically placed into the stomach and electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. Animals received a daily injection of neutralizing NGF antibody or control serum for 5 days. NGF in the stomach wall was measured with an ELISA. The severity of gastric injury was assessed macroscopically and by determination of myeloperoxidase (MPO) activity. Gastric injury enhanced the visceromotor response to GD and increased NGF content. Anti-NGF significantly blunted the development of hyperalgesia and led to a decrease in gastric wall thickness and MPO activity. Increases in NGF contribute to the development of hyperalgesia after gastric injury. This may be partly mediated by direct effects on afferent nerves and indirectly by modulatory effects on the inflammatory response. [source] Experimental study of the safety of the selective COX-2 inhibitor, celecoxib, for gastric mucosaJOURNAL OF DIGESTIVE DISEASES, Issue 2 2003Jun Ting LI OBJECTIVE: To compare the gastric mucosal damage induced by a COX-2 inhibitor, celecoxib, and a conventional NSAID, indomethacin. METHODS: A rat model of NSAID-induced gastric mucosal damage was prepared for indomethacin and celecoxib separately (n = 8). After gastric damage was induced by 100% ethanol, celecoxib was administered by gastric gavage (n = 8). Gastric mucosal concentrations of 6-keto-PGF1, and TXB2 and the lesion index (LI) were measured. Morphological changes of the gastric mucosa were assessed under light and scanning electron microscopy. RESULTS: Indomethacin caused marked gastric damage (LI: 13.38 ± 2.06) and significant reduction of the concentrations of 6-keto-PGF1, and TXB2 (P < 0.01), Celecoxib did not produce necrotic injuries on healthy gastric mucosa (LI: 0), but the mucosal injuries previously induced by ethanol worsened after its administration (LI: 37.19 ± 3.34 vs 19.90 ± 2.28, P < 0.01). CONCLUSIONS: Inhibition of COX-1 is the major mechanism of NSAIDs in producing gastric mucosal damage. As a selective COX-2 inhibitor, celecoxib does not produce toxic injuries of the healthy gastric mucosa, and is thus safer than conventional NSAID. However, when administered in the presence of an altered gastric mucosa, gastric injuries were worsened. [source] Willow bark extract and aspirin , their potential for gastric injury in mice and other toxicity aspectsFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 1 2002EI Dabrowska-Zamojcin [source] Evaluation of gastric toxicity of indomethacin acid, salt form and complexed forms with hydroxypropyl-,-cyclodextrin on Wistar rats: histopathologic analysisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009A.C. Ribeiro-Rama Abstract Indomethacin (IM) is a non-steroidal anti-inflammatory drug which inhibits prostaglandin biosynthesis. It is practically insoluble in water and has the capacity to induce gastric injury. Hydroxypropyl-,-cyclodextrin (HP-,-CD) is an alkylated derivative of ,-CD with the capacity to form inclusion complexes with suitable molecules. IM is considered to form partial inclusion complexes with HP-,-CD by enclosure of the p -chlorobenzoic part of the molecule in the cyclodextrin channel, reducing the adverse effects. The aim of this paper is to evaluate the gastric damage induced by the IM inclusion complex prepared by freeze-drying and spray-drying. A total of 135 Wistar rats weighing 224.4 ± 62.5 g were put into 10 groups. They were allowed free access to water but were maintained fasted for 18 h before the first administration until the end of the experiment. IM acid-form, IM trihydrated-sodium-salt and IM-HP-,-CD spray and freeze-dried, at normal and toxic doses, were administered through gastric cannula once/day for 3 days. Seventy-two hours after the first administration, the animals were sacrificed and the stomachs collected and prepared for morphological study by using the haematoxylin-eosin technique. Lesion indexes (rated 0/4) were developed and the type of injury was scored according to the severity of damage and the incidence of microscopic evidence of harm. Microscopic assessment demonstrated levels of injury with index one on 10,25%. The type of complexation method had different incidence but the same degree. The results show that IM inclusion complexation protects against gastric injury, reducing the incidence and the maximum degree of severity from 4 to 1, with a better performance of the spray-dried complex. [source] Gastrointestinal effects of nonsteroidal anti-inflammatory drugsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2003Brendan J. R. Whittle Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) causes extensive damage to the gastrointestinal (GI) tract. The underlying mechanisms of gastric injury include topical irritant actions that disrupt the epithelial barrier, as well as the inhibition of cyclo-oxygenase (COX), which is predominantly the COX-1 isoform in the mucosa. This damage can be attenuated by antisecretory agents or by mucosal protective agents such as the synthetic prostanoids or nitric oxide (NO) donors. Compounds designed to attenuate topical irritancy, or have protective agents incorporated, such as NO-containing NSAIDs, the CINODs (cyclo-oxygenase-inhibiting NO-donating drugs) show reduced mucosal injury. NSAIDs also cause injury in the small intestine, which appears to result from initial COX inhibition, with subsequent translocation of indigenous bacteria, induction of NO synthase and production of the cytotoxic moiety, peroxynitrite. The COX-2 selective agents, the coxibs, which inhibit prostanoid biosynthesis at inflammatory sites, but not the endogenous protective prostanoids in the gut formed by COX-1, have proved so far to be a successful therapeutic approach to reducing NSAIDs GI damage. The clinical outcome of the use of the second generation of coxibs, and the newer NO NSAIDs is now awaited. [source] Cyclo-oxygenase-2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2000Wei-Hao Sun Abstract Background and Aims: The present study examined the effects of NS-398, a specific cyclo-oxygenase-2 inhibitor, on gastric mucosal cell kinetics and gastric wound healing following acid-induced injury. Methods: Male Sprague-Dawley rats were fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered into the stomach; NS-398 or indomethacin was administered to the animals 10 min after the acid. Levels of constitutive cyclo-oxygenase (COX-1) and mitogen-inducible cyclo-oxygenase (COX-2) in the gastric mucosa were analysed using western blotting and immunohistochemical staining. The grade of the lesion was assessed using planimetry and histological examination, including immunohistochemistry for proliferating cell nuclear antigen (PCNA). Results: Although there was strong expression of COX-1, there was minimal expression of COX-2 in the gastric mucosa. Expression of COX-2 was enhanced mainly in surface epithelial cells and neck cells following HCl administration. Gastric mucosal ulcers and erosions healed within 48 h, during which time the proliferative zone expanded in the control animals. Indomethacin and NS-398 suppressed the expansion of the proliferative zone and delayed the healing of the gastric injury. Conclusion: The present study demonstrated that cyclo-oxygenase-2 inhibitors delay gastric wound healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclo-oxygenase-2 has an important role in gastric mucosal regeneration. [source] The role of erythropoietin in the protection of gastric mucosa from indometacin-induced gastric injury and its relationship with oxidant and antioxidant parameters in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2010Fatih Albayrak Abstract Objectives Erythropoietin has anti-oxidative and anti-inflammatory activity. We wanted to evaluate its activity in preventing damage to the gastric mucosa. Methods We examined the protective effect of erythropoietin on indometacin-induced gastric mucosa damage in the rat stomach and compared its potency with that of famotidine. We also measured effects on oxidant and antioxidant parameters in the rat stomach. Key findings Famotidine and erythropoietin 2500 and 5000 IU/kg reduced the ulcer area by 98%, 31% and 58%, respectively, compared with the indometacin group. Superoxide dismutase activity and glutathione level were decreased and myeloperoxidase activity increased in the indometacin group compared with healthy rats. Famotidine and erythropoietin at all doses increased superoxide dismutase and glutathione levels significantly compared with the indometacin group. Myeloperoxidase activity was decreased by erythropoietin and famotidine. Conclusions These results support the view that erythropoietin counteracts the effects of indometacin in inducing gastric ulcer and could be used as a an antiulcer compound. Its antiulcer effect is less potent than that of famotidine. The antiulcerogenic effects of erythropoietin may be related to its intrinsic ability to sustain the activities of free-radical scavenging enzymes and the bioavailability of glutathione. [source] Nerve growth factor and gastric hyperalgesia in the ratNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2003K. Lamb Abstract We recently demonstrated an association between the development of hyperalgesia and an increase in nerve growth factor (NGF) during gastric inflammation. We hypothesized that block of NGF signalling will blunt injury-induced hyperalgesia. Male Sprague,Dawley rats (300,400 g) were anaesthetized, the stomach was exposed and placed in a circular clamp. Acetic acid (60%) or saline (control) was injected into this area and aspirated 45 s later, resulting in kissing ulcers. A balloon was surgically placed into the stomach and electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. Animals received a daily injection of neutralizing NGF antibody or control serum for 5 days. NGF in the stomach wall was measured with an ELISA. The severity of gastric injury was assessed macroscopically and by determination of myeloperoxidase (MPO) activity. Gastric injury enhanced the visceromotor response to GD and increased NGF content. Anti-NGF significantly blunted the development of hyperalgesia and led to a decrease in gastric wall thickness and MPO activity. Increases in NGF contribute to the development of hyperalgesia after gastric injury. This may be partly mediated by direct effects on afferent nerves and indirectly by modulatory effects on the inflammatory response. [source] Antiulcerogenic effect of Hippophae rhamnoides L.PHYTOTHERAPY RESEARCH, Issue 7 2001H. Süleyman Abstract The antiulcerogenic effect of a hexane extract (HRe-1) from Hippophae rhamnoides (Eleagnaceae) was tested on indomethacin- and stress-induced ulcer models. As a result HRe-1 was found to be active in preventing gastric injury. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||