Gastric Mucosal Ulceration Research Articles

Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages

Aims Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredients in Stillen TM, a drug for the gastric mucosal ulcers. Eupatilin has been known to possess anti-peptic, anti-cancer, and anti-allergy activity. In this report, we defined the effect of eupatilin on the endotoxin-induced inflammation in lipopolysaccharide (LPS)-stimulated macrophages. Main methods Mouse J774A.1 cell line and mouse peritoneal macrophages were used. Gene expression and production of inflammatory mediators were determined by real-time PCR and Western blot. Key findings Eupatilin dose-dependently suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Eupatilin decreased LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines such as cyclooxygenase-2, monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In addition, this suppression of inflammatory mediators was nuclear factor (NF)-κB dependent. Significance Our findings imply that eupatilin suppresses inflammatory responses by the inhibition of NF-κB signaling pathway, and downstream inflammatory mediators in endotoxin-stimulated macrophages.

Role of acid back-diffusion in the formation of mucosal ulceration and its treatment with drugs in diabetic rats.

We have studied the role of acid back-diffusion in the formation of gastric mucosal ulceration and its treatment with several drugs in streptozotocin-induced diabetic rats. After vagotomy, the stomach of 1-8 week-old diabetic rats and age-matched control rats were irrigated with acid solutions of graded concentrations (50-150 mm HCl) for 1 or 3 h. A marked increase in acid back-diffusion and in haemorrhagic ulceration was found in diabetic rats. The extent of acid back-diffusion and the severity of mucosal ulceration were dependent on the concentration and the time of contact of acid solutions with the gastric mucosa. A high correlation (r = 0.9227) between acid back-diffusion and mucosal ulceration was found in 3-h acid-irrigated diabetic rats. In the 2-week diabetic rat, intragastric cimetidine (300 mg kg-1) or NaHCO3 (52 mg kg-1) significantly (P < 0.05) reduced both acid back-diffusion and haemorrhagic ulcer formation, while atropine (1.0 mg kg-1) or bupivacaine (0.5%, 0.4 mL/rat) was ineffective. High blood glucose levels in diabetic rats were not influenced by these agents. Acid back-diffusion and ulceration in the diabetic rat were markedly reduced by daily administration but not single injection of insulin (50 units kg-1, s.c.). Taken together, in the early stage of diabetes development, chronic insulin deficiency rather than nerve degeneration or hyperglycaemia may be responsible for the disruption of mucosal barriers. It is concluded that acid back-diffusion played an important role in the formation of acute haemorrhagic ulceration that can be inhibited by intragastric cimetidine, NaHCO3 or daily injection of insulin.

Gastric mucosal ulceration induced in pigs by tabelts but not suspensions or solutions of aspirin.

Gastric mucosal ulceration induced in pigs by tabelts but not suspensions or solutions of aspirin.

Dual effects of zinc sulphate on ethanol-induced gastric injury in rats: possibly mediated by an action on mucosal blood flow.

The present study examines the protective effect of zinc sulphate against ethanol-induced gastric mucosal ulcers in rats. Absolute ethanol decreased the gastric mucosal blood flow and produced haemorrhagic lesions in the glandular mucosa. Zinc sulphate preincubation in an ex-vivo stomach chamber preparation prevented the formation of ethanol-induced lesions and attenuated the decrease of blood flow produced by ethanol. Subcutaneous injection of the same doses of the drug at 15 and 30 min before ethanol exposure, markedly reduced the blood flow and also aggravated ethanol-induced gastric injury; however, when injected at 23 and 24 h before ethanol administration, zinc sulphate protected against lesion formation but had no effect on the vascular changes induced by ethanol in the gastric glandular mucosa. These findings show that the antiulcer effect of zinc sulphate occurs only when the drug is given orally, or injected s.c. 23 and 24 h before ethanol challenge. Furthermore, this protective action is probably not entirely mediated by preservation of the gastric mucosal blood flow.

Acute and twenty-eight days repeated oral dose toxicity study of besifloxacin in Wistar albino rats

The purpose of this study was to investigate the potential acute and 28-day repeated oral toxicities of besifloxacin (BAF) in Wistar albino rats. In oral acute and repeated dose study, BAF was administered to both sex of rats, at dose levels of 0, 300, 600, 900 mg/kg/day and 0, 100, 200, 500 mg/kg/day, respectively. In the acute study, total white blood cell (WBC) (male, 43.74%; female, 42.60%) and total bilirubin (T-BIL) (male, 80%; female, 60%) were significantly increase, total protein (TP) (male, 23.24%; 27.80%) was significantly decreased, and significant incidence of pericholangitis (male, 83.33%; female, 75%) was shown in males and females of high-dose groups. In repeated oral dose toxicity study, similar type effects were also observed after serum hematological and serum biochemical analysis, whereas additionally sever hepatic injury and focal ulceration in gastric mucosa also observed in high dose groups of both sexes after histopathological analysis. However these toxic effects of besifloxacin were transient and reversible and no-observed adverse effect level (NOAEL) were 300 mg/kg/day for acute and 100 mg/kg/day for repeated dose toxicity study, respectively.

Cyclooxygenase-2 mRNA expression in equine nonglandular and glandular gastric mucosal biopsy specimens obtained before and after induction of gastric ulceration via intermittent feed deprivation

To measure the expression of cyclooxygenase-2 (COX-2) mRNA in gastric biopsy specimens serially obtained from horses before, during, and after an 8-day intermittent feed-deprivation trial and to investigate the mucosal location of COX-2. 9 mixed-breed horses for retrieval of gastric biopsy specimens and 16 additional horses for immunohistochemical analysis. Gastric biopsy specimens were obtained from 6 horses; 3 of these horses and 3 more participated in an intermittent feed-deprivation trial 9 weeks later. A quantitative PCR assay was used to determine the amount of COX-2 mRNA in biopsy specimens from nonulcerated and ulcerated gastric mucosa. Immunohistochemical staining of specimens by use of a polyclonal anti-COX-2 antibody was performed on full-thickness postmortem gastric biopsy specimens. COX-2 mRNA was expressed in all glandular gastric mucosal specimens but was only detectable in nonglandular mucosal specimens when ulceration was present or during ulcer healing. Positive staining for COX-2 was present in 12 of 14 nonulcerated glandular mucosal sections. Although such staining was weak or absent in nonulcerated nonglandular sections, stronger staining was evident in regenerating epithelium at the rims of erosions and ulcers. COX-2 was constitutively present in equine glandular gastric mucosa, although its contribution to mucosal protection remains unclear. Our finding of COX-2 mRNA expression in ulcer margins during healing may support a role for the products of this enzyme in mucosal repair. The potential roles of COX-2 should be considered when COX-2-selective inhibitors are prescribed for horses with gastric ulcers.

Abarema cochliacarpos: Gastroprotective and ulcer-healing activities

Abarema cochliacarpos (Gomes) Barneby & Grimes (Mimosaceae) is a species--in folk medicine of Lagarto city, Sergipe state, northeastern Brazil--reputed to heal gastric ulcer and gastritis. Chloroform (CE) and methanolic (ME) extracts as well as ethyl acetate fraction (AF), butanolic fraction (AC) and aqueous fraction (AQF) of the methanolic extract of Abarema cochliacarpos bark were evaluated against acute gastric ulcer. The AC fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion. The gastroprotective action of CE and ME extracts and the fractions of the latter were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action and mucus production, toxicological and healing activity of the AC (150 mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA, COX-2, VEGF and HSP-70) assays to evaluate the effects of Abarema cochliacarpos. CE (200 and 400 mg/kg, p.o.) and ME (100, 200 and 400 mg/kg, p.o.) extracts were able to protect gastric mucosa against absolute ethanol. Respective inhibitions produced were: 65.31% and 83.80% by the first; 91.69%, 96.75% and 99.80% by the second; and 74.24% by the AC fraction. Antisecretory and mucus production effects were exhibited by the AC fraction, which also accelerated the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA) and induced healing factors including COX-2, VEGF and HSP-70. All these results suggest that Abarema cochliacarpos (Gomes) Barneby & Grimes presents gastroprotective effects and wound-healing properties.

Thrombotic microangiopathy and the antiphospholipid syndrome

The antiphospholipid syndrome (APS) comprises the association between vascular thrombosis, including microthrombosis, pregnancy morbidity and the coexistence of anti-phospholipid antibodies. Thrombotic microangiopathy (TMA) can be one of the manifestations of the APS and may involve any organ. This feature of the APS is probably less recognized by clinical doctors than venous thrombosis and recurrent abortions. This case report presents a patient who developed a widespread TMA with renal failure, gastric mucosa ulceration, urinary bladder ulcerations and a finger necrosis as part of the APS.

Twenty-eight days repeated oral dose toxicity study of gemifloxacin in Wistar albino rats

The purpose of this study was to investigate the potential toxicity of gemifloxacin by 28-day repeated oral dose in Wistar albino rats. The test article, was administered daily by gavage to male and female rats at dose levels of 0, 50, 100, 200 mg/kg/day. At the end of treatment period, 12 rats/sex/group was sacrificed, while six extra rats/sex in the vehicle control and highest dose groups sacrificed after 14 days recovery period. During the treatment and recovery periods, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, phototoxicity, hematology, serum biochemistry, synovial fluid biochemistry, electrocardiogram (ECG), gross findings, organ weights, microscopic examination of synovial fluid, and histopathology were examined. Hematological and serum biochemical investigations revealed a dose-dependent increase in the total white blood cell (WBC), total bilirubin (T-BIL), glucose (GLU), alanine aminotransferase (ALT) and significant decreases in total protein (TP) were observed in both sexes at the same dose, at the end of treatment period, but the levels returned toward normal during the recovery period. Histopathology of talar joint showed that erosion of the articular surface of that joint in both sexes at the end of treatment period at the dose level of 200 mg/kg/day. Degenerative changes in tendinocytes were observed in Achilles tendon of both sexes at the high dose level at the end of treatment period. In histopathological study shows partial effacement of liver architecture and focal ulceration in gastric mucosa at the high dose level at the end of treatment period. Based on these results, it was concluded that 28 days repeated oral dose of gemifloxacin caused increases in the liver weight, WBC count, T-BIL, glucose level, ALT, decreasing the TP, cause chronic hepatitis and acute gastritis, erosion of the articular surface of joint and histopathologic changes in Achilles tendon in rats at the dose level of 200 mg/kg/day.

Natural history of chronic gastritis in a population-based cohort

Objective. To describe and explore the natural history of Helicobacter pylori infection and chronic gastritis in terms of gastric mucosal atrophy and ulcer development over time in a population-based cohort. Material and methods. A population-based cohort of 314 volunteers was re-screened (median follow-up interval of 8.4 years) with gastroduodenoscopy with biopsy, assessment of H. pylori status, analysis of pepsinogens, and monitoring of a nonsteroidal anti-inflammatory drug (NSAID) use and alcohol and smoking habits. Results. The incidence of duodenal or prepyloric ulcer was 0.45 per 100 person years and was associated with weekly NSAID use (odds ratios, OR 27.8), weekly alcohol consumption (OR 19.4) and smoking (OR 31.0), but not with H. pylori status. De novo infection with H. pylori was not observed, and the infection had disappeared in 11 of 113 subjects. Among subjects with chronic gastritis, the incidence of atrophy of the corpus mucosa was 1.4 per 100 person years. Atrophy development was related to age (OR 1.23) and to the severity of chronic inflammation in the corpus mucosa at baseline (OR 8.98). Substituting atrophy for subnormal S-pepsinogen I/S-pepsingen II gave similar results. Conclusions. In this cohort, the minimum incidence of ulcer was 0.45 per 100 person years. Smoking, alcohol, and NSAIDs, but not H. pylori infection were significant risk factors. The incidence of atrophy of the corpus mucosa was 1.4 per 100 person years with a positive relation to age and to the degree of chronic inflammation at baseline. Atrophy was stationary in advanced stages.

Asymptomatic Meckel's diverticulum in adults: is diverticulectomy indicated?

Background/Aim:The objective of this study was to estimate the incidence of the Meckel’s diverticulum (MD) and to study its clinical profile and surgical outcome, as well as to check whether diverticulectomy is indicated for asymptomatic MD in adults.Materials and Methods:This is a prospective study of 1332 patients who were operated upon for acute abdomen during the period August 1999 to July 2009 in a single surgical unit. Preoperative abdominal ultrasonography and plain x-ray abdomen (erect) were done depending on the necessity. These patients were subjected to laparotomy/ appendicectomy depending on the case. A search for MD was done, and if found, surgical resection and analysis by histopathological confirmation of the resected MD were performed.Results:During the operation, this study detected 15 (1.13%) patients with MD. In none of these cases, preoperative diagnosis of Meckel’s diverticulitis was made. The age of the patients ranged from 18 to 68 years (mean age, 32.9 years). Out of 15 patients, 9 (60%) were males; 6 (40%) were females. Seven (46.7%) cases were symptomatic due to MD and 8 (53.3%) were asymptomatic. One patient presented with hematochezia; 2, with intestinal obstruction due to gangrene of the MD; and 4, with Meckel’s diverticulitis. One patient had duplication of (double) Meckel’s diverticulum without any inflammation in both the diverticulae. Histopathological examination of these specimens confirmed 4 cases with inflammation; 2, with gangrene; and 1, with ulcerated gastric mucosa in the MD. Among these, in 2 (13.3%) cases there was heterotopic epithelium (ulcerated gastric mucosa- 1, colonic mucosa- 1).Conclusion:We recommend that a search for MD in every case of appendicectomy/ laparotomy done for acute abdomen should be conducted, and if found, Meckel’s diverticulectomy or resection should be performed to avoid secondary complications arising from it.

The 5-HT4 receptor agonist mosapride attenuates NSAID-induced gastric mucosal damage

The cholinergic anti-inflammatory pathway is a novel physiological mechanism found at various locations in the body where the nicotinic regulation of inflammatory cells through the autonomic nervous system is involved. In this study, we tested the hypothesis that cholinergic nerve stimulation by a 5-HT(4) agonist may modulate the progression of gastric mucosal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Acute gastric ulcers were induced in rats by the oral administration of indomethacin. Gastric damage analysis indicated that pretreatment with mosapride, a selective 5-HT(4) agonist, at 0.25, 0.5, and 0.75 mg/kg, inhibited the mucosal damage induced by indomethacin. In gastric emptying analysis, an evacuation effect was observed in the 3.0 mg/kg mosapride pretreatment group, but this effect was not observed in the lower dose (0.5 mg/kg) group. The antiulcerogenic activity of mosapride treatment (at 0.5 mg/kg) was blocked by a 5-HT(4)-specific antagonist, GR113808 (1 mg/kg, i.v.). Additionally, we demonstrated that methyllycaconitine (0.29 and 0.87 mg/kg i.p.), a selective inhibitor of alpha7 nicotinic acetylcholine (ACh) receptors (alpha7nAChRs), ablated the antiulcerogenic action of mosapride. These results suggest that the mucosal protective action of mosapride may be mediated by an action on immune cells through the acceleration of ACh release from parasympathetic nerves via the activation of 5-HT(4) receptors, followed by activation of the nicotinic anti-inflammatory system. It appears that the alpha7nAChR may be involved in the antiulcerogenic action of mosapride.

Risk factors for the development of gastric mucosal lesions in rheumatoid arthritis patients receiving long-term nonsteroidal anti-inflammatory drug therapy and the efficacy of famotidine obtained from the FORCE study

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury, and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.

Sesame lignan sesamol protects against aspirin-induced gastric mucosal damage in rats

Non-steroidal anti-inflammatory drugs are commonly used to control pain, fever, and various inflammatory diseases; however, they have been identified as gastro-toxic. The aim of the present study was to evaluate the effect of aspirin plus sesamol on gastric mucosa in rats. Rats were given oral aspirin (30 mg/kg/d) and oral sesamol (ranging from 0 to 30 mg/kg/day) for 5 weeks, after which their gastric mucosal integrity, oxidative stress, inflammation, and neutrophil infiltration were assessed 6 h after gastric surgery. Sesamol dose-dependently decreased aspirin-induced gastric haemorrhage and mucosal ulceration, and significantly reduced (a) gastric mucosal lipid peroxidation, (b) nitric oxide production, (c) gastric mucosal proinflammatory cytokines (tumor necrosis factor-α and interleukin 1-β levels), and (d) the activity of gastric mucosal myeloperoxidase compared with aspirin-alone groups. We hypothesize that aspirin plus sesamol decreases aspirin-induced gastro-toxicity by inhibiting neutrophil infiltration and subsequent gastric mucosal inflammation and oxidative stress in rats.

Risk factors for the development of gastric mucosal lesions in rheumatoid arthritis patients receiving long-term nonsteroidal anti-inflammatory drug therapy and the efficacy of famotidine obtained from the FORCE study

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury,and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.

Massive gastric necrosis from hydrochloric acid ingestion

Severe gastrointestinal-tract injury due to ingestion of caustic substances is not an infrequent problem in the emergency department. We report the case of a 57-year-old male who developed massive hemorrhagic, caustic gastric necrosis due to the ingestion of a non-diluted solution containing hydrochloric acid, which propitiated an urgent surgical procedure. The esophago-gastrectomy specimen showed extensive hemorrhagic gastric necrosis with important damage to the gastric wall in the histopathological evaluation. The ingestion of caustic substances is a medical problem that is still frequent in emergency departments, either by mistake or with suicidal purposes. The extent and the severity of tissue damage vary according to different factors related to substance type, amount and concentration, as well as other personal factors. We report the case of a 57-year-old male who ingested 20 cc of a non-diluted solution containing hydrochloric acid as a suicide attempt three hours before he was admitted to our hospital. After that he had experienced vomiting with emission of black sloughs. He was clinically and hemodynamically stable with only intense epigastric pain. An ORL exploration and chest and abdominal radiographs showed no complication signs. An urgent gastroscopy revealed that the esophageal mucosa was not necrotic but ulcerated in some areas. In the esophago-gastric junction a transition to an ulcerated gastric mucosa could be seen, with severe diffuse hemorrhagic necrosis and sloughs that easily fell off with endoscope maneuvers (Fig. 1) compatible with grade-3 caustic gastritis according to Zargar’s classification (1). The duodenum was not explored because of perforation risks. An urgent surgical intervention was performed due to the high risk of perforation. The esophagus was ulcerated and the stomach had extensive areas of necrosis, so partial esophagectomy and total gastrectomy were performed to avoid the risk of future complications, doing an esophagostomy and terminal ileostomy. The histopathological analysis of the surgery specimen showed extensive hemorrhagic gastric

Mouririelliptica: Validation of gastroprotective, healing and anti- Helicobacter pylori effects

Ethnopharmacological relevance Mouriri elliptica Martius (Melastomataceae) is species reputed in folk medicine to heal gastric ulcer and gastritis. Aim of the study Methanolic extract (ME) and ethyl acetate fraction (EAF) from leaves of Mouriri elliptica were evaluated for their gastroprotective, healing, immunological, toxicological and anti- Helicobacter pylori activities. Material and methods The gastroprotective action of ME and EAF was evaluated in rodent experimental models and to elucidate mechanisms of action, the antisecretory action, involvements of NO, SH, PGE 2, anti- Helicobacter pylori action of ME was evaluated. We also used immunohistochemical (PCNA and COX-2) and immunomodulatory (murine peritoneal macrophages) assays to evaluate Mouriri elliptica effects. Results ME present gastroprotective action without antisecretory effect. Otherwise, ME showed anti- Helicobacter pylori action (MIC = 0.025 μg/mL) and was able to inhibit NO production by macrophages. This species also accelerate the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA), COX-2 and maintained basal PGE 2 level independent action of NSAID in gastric mucosa. The phytochemical investigation showed that this species possesses phenolic acid derivatives, acylglycoflavonoids and condensed tannins which probably influenced their pharmacological action. Conclusion All these results suggest the efficacy and safety of Mouriri elliptica in combating and healing gastric ulcer.

Ammonium Glycyrrhizinate Protects Gastric Epithelial Cells from Hydrogen Peroxide-Induced Cell Death

Glycyrrhiza uralensis has a potential for preventing or ameliorating gastric mucosal ulceration. To understand the molecular mechanism about the medicinal effect of G. uralensis, we isolated four single compounds from G. uralensis and one related compound and screened for the cellular protective effect against H(2)O(2)-induced damage in gastric epithelial AGS cells. Interestingly, we found that ammonium glycyrrhizinate (AG) prepared from glycyrrhizin dramatically protects AGS cells from H(2)O(2)-induced damage as measured by the integrity of actin cytoskeleton. AG also inhibited FeSO(4)-induced reactive oxygen radicals in a dose-dependent manner, suggesting the role for AG as a free radical scavenger. To better understand the protective role of AG at the transcriptional level, we performed genome-wide expression profiling using high-density oligonucleotide microarrays, followed by validation using RT-PCR. Among the 33,096 genes that were screened in the microarray, 936 genes were found to be differentially expressed in a statistically significant manner in the presence or absence of H(2)O(2) and AG. Among the 936 genes, 51 genes were differentially expressed at least 3-fold in response to the H(2)O(2) treatment. AG blocked the expression of genes related to apoptotic cell death (GDF15, ATF3, TNFRSF10A, NALP1) or oxidative stress path-ways (HMOX1) which was elevated in response to H(2)O(2) treatment, suggesting a potential protective role for AG in oxidative stress-induced cell death. Collectively, current results demonstrate that AG is a novel antioxidant that could be effective for the treatment of gastric diseases related to the oxidative stress-induced mucosal damage.

Comparative antiulcer effect of Bisdemethoxycurcumin and Curcumin in a gastric ulcer model system

The antiulcer effect of bisdemethoxycurcumin, a yellow pigment found mainly in rhizomes of Curcuma longa, was compared with curcumin in gastric ulcer model systems to validate its clinical application as a remedy for peptic ulcer. Western blot analysis of mouse macrophage cell line RAW 264.7 activated with lipopolysaccharide showed that bisdemethoxycurcumin inhibited inducible nitric oxide synthase (iNOS) production significantly but had no effect on tumor necrosis factor-alpha (TNF-alpha) production, whereas curcumin showed stronger suppression of iNOS protein production and inhibited TNF-alpha protein production significantly. However, bisdemethoxycurcumin and curcumin possessed similar potency in scavenging nitric oxide generated from mouse macrophage cell line RAW 264.7. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that both curcuminoids inhibited the induction of iNOS dose-dependently at the transcriptional level and curcumin also appeared to inhibit the induction of TNF-alpha at post-transcriptional level. In an animal model, intraduodenal administration of bisdemethoxycurcumin (5-80 mg/kg body wt.) showed a strong inhibitory effect on gastric acid secretion in pylorus-ligated rats whereas curcumin (5-20 mg/kg body wt.) showed a less inhibitory effect, with maximum potency at a dose of 20mg/kg body wt. Moreover, oral administration of bisdemethoxycurcumin at doses of 20-80 mg/kg body wt. twice daily for 10 days showed a significant curative efficacy in accelerating the healing of acetic acid-induced chronic gastric ulcer and promotion of mucosal regeneration in the ulcerated portion in a dose-related manner with potency equal to curcumin. In contrast, the curative potency of curcumin tended to decrease at doses over 160 mg/kg body wt./day. Western blot analysis in ulcerated gastric mucosa showed that bisdemethoxycurcumin dose-dependently reduced the increased protein expression level of iNOS but not TNF-alpha. These results indicated that bisdemethoxycurcumin directly accelerates gastric ulcer healing with potency equal to curcumin. Its antiulcer effect might be due to its properties of decreasing gastric acid secretion and enhancing the mucosal defensive mechanism through suppression of iNOS-mediated inflammation.

Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor

To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage. Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively. There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 +/- 3.49, and mean ulcer area; 21.00 +/- 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 +/- 2.47, P > 0.05), 20 mg/kg (2.37 +/- 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 +/- 3.06), and vardenafil 10 mg/kg (1.25 +/- 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 +/- 2.97, P < 0.001) , famotidine 20 mg/kg (0.94 +/- 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 +/- 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 +/- 0.88, P < 0.001) compared to the indomethacin group. MDA levels were significantly higher in indomethacin group (28.48 +/- 14.51), compared to the famotidine 5 mg/kg (6,21 +/- 1.88, P < 0.05), famotidine 20 mg/kg (5.88 +/- 1.60. P < 0.05), vardenafil 2 mg/kg (15.87 +/- 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 +/- 4.50, P < 0.05). NO concentration in gastric tissues of the famotidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed diminished gastric damage for pretreatment groups compared to the indomethacin group (P < 0.05). Vardenafil affords a significant dose-dependent protection against indomethacin induced gastric mucosal lesions in rats.