Effects of Aloe vera and sucralfate on gastric microcirculatory changes,cytokine levels and gastric ulcer healing in rats

AIM： To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS： Male Spraque-Dawley rats （n=48） were divided into four groups. Group 1 served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-α and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. RESULTS： On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly （P〈 0.05） increased in the ulcer groups when compared to the control group. The level of TNF-α was elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-a had no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-α were still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-α level. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. CONCLUSION： Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-α level and reduce IL-10 level. Aloe vera treatment can reduce leukocyte adherence and TNF-αlevel, elevate IL-10 level and promote gastric ulcer healing.

Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents

AIM： To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions （HML） and the mechanism of gastroprotective effect of sucralfate.METHODS： Rats were given 1 mL of 75% ethanol, 25%NaCl, 0.6 mol/L HCI, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically （i.g.） and sacrificed 1, 3, 6 or 12 min later. Total （reduced and oxidized） glutathione （GSH ＋ GSSG）, glutathione disulfide （GSSG）, protein free sulfhydryls （PSH）, protein-glutathione mixed disulfides （PSSG） and protein cystine disulfides （PSSP） were measured in gastric mucosa and liver.RESULTS： Reduced glutathione （GSH） was depleted in the gastric mucosa after ethanol, HCI or NaCl exposure,while oxidized glutathione （GSSG） concentrations increased, except by HCI and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed,NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals.No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.CONCLUSION： Our modified methods are now suitable for direct measurements of major protein and nonprotein thiols/disulfides in the gastric mucosa or liver.A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.

High-potency sucralfate prevents and rapidly reverses chemo-radiation mucositis in a patient with stage 4b head and neck cancer

AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.

Is there still a role for sucralfate in the treatment of gastritis?

The endoscopic diagnosis of gastritis is usually made when a patient develops symptoms and undergoes an upper gastrointestinal endoscopy.There are often obvious aetiological causes such as smoking,alcohol Helicobacter pylori infection or drug treatment.Lifestyle changes can sometimes improve symptoms but often patients will be treated with a proton pump inhibitor.The stomach mucosa produces a protective mucous to prevent damage cause by gastric acid and exogenous agents can disrupt this layer.Repair of this protective layer can be enhanced by reduction in gastric acid secretion using H2 receptor antagonist or proton pump inhibitors or by cytoprotective drugs such as misoprostol,sucralfate,aluminium ions or bismuth subsalts.Sucralfate is a complex polymer which at a low pH changes its chemical configuration and binds to serum protein to form a protective layer protecting the mucosa against further injury.Cytoprotective drugs were the first line treatment for peptic disease including gastritis for many years but since the launch of cimetidine in 1976 and the subsequent launch of omeprazole in 1988,their use has slowly declined.First line treatment for patients with symptomatic gastritis after removal of potential causative factors is likely to be a proton pump inhibitor in 2019.This is despite the fact that there is some evidence that sucralfate is superior than a H2 receptor antagonist in the endoscopic healing rates in patients with gastritis.The logical treatment choice in patients with resistance symptoms is a combination of a proton pump inhibitor and sucralfate but evidence is lacking.Until such evidence is available In the meantime,we would suggest that there is a role for sucralfate in the treatment of intransigent gastritis and that mucosal protection should be considered even ahead of acid suppression given its favourable safety and toxicity profile.

Expedited Management of Canine and Feline Vomiting and Diarrhea. Observational Study in 3952 Dogs and 2248 Cats Using Sucralfate-Like Potency-Enhanced Polyanionic Phyto-Saccharide—Elm Mucilage

A potency-enhanced polyanionic phyto-saccharide of elm mucilage (PEPPS) was prescribed by 197 small animal veterinarians in an open-labeled field trial. Clients provided informed consent to veterinarians to prescribe PEPPS to 3952 dogs and 2248 cats. A 2 day/4 dose response rate, determined by veterinarians’ consensus, provided clinical threshold for a significant clinical outcome. Data was collected through phone interviews conducted over a period of 3.5 years from June 2003 through December 2006. 82% of 1928 vomiting dogs and 77% of 1064 vomiting cats responded to PEPPS within 2 days or four doses. 93% of 2024 dogs and 79% of 1184 cats with diarrhea responded to PEPPS within 2 days or four doses. PEPPS appears useful for managing vomiting and diarrhea in dogs and cats. However, a randomized blinded placebo controlled trial is needed to quantify true clinical efficacy.

Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis

Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.

Protective Effect of Holothurian Intestine Against Indomethacin Induced Gastric Mucosal Damage in Rats

Our study aimed to investigate the protective effects of Holothurian intestines(HI) on NSAIDs-induced gastric mucosal damage and the possible mechanism. At first, 60 male Wistar rats were induced of gastric lesions with indomethacin(IDM, 30 mg kg^(-1)). The rats were pretreated for 15 consecutive days with saline, sucralfate, or HI(0.4g kg^(-1) d-1, 0.8 g kg^(-1) d^(-1) and 1.6 g kg^(-1) d^(-1)) prior to IDM treatment, followed by evaluations of macroscopic damage and microscopic features; and investigation of the levels of inflammatory cytokines, oxidative stress parameters, gastric mucosal prostaglandin E2(PGE2) and total hexosamine in tissues. The expression of COX-1 and COX-2 m RNA in the gastric tissue were determined by quantitative polymerase chain reaction(q PCR). Pathological gastric ulcer indexes, levels of pro-inflammatory cytokines(IL-1β, IL-17, TNF-α) and lipid peroxidation were significantly decreased in HI-treated groups, whereas the levels of protective factors(TGF-β, GSH, SOD activity and PGE2) were significantly elevated especially in the group with HI 1.61 g kg^(-1) d^(-1)(P < 0.05). Furthermore, the expression of COX-2 mRNA decreased significantly in HI groups(P < 0.05). The study investigates that holothurian intestines may act as a kind of marine medicine which have protective effect on IDM-induced gastric ulcer, which could be a dietary preventive agent for the prevention of gastric damage.

Prevention of pelvic radiation disease

Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes radiotherapy. Gastrointestinal(GI) radiation-induced toxicity is a major complication and the transient or long-term problems, ranging from mild to very severe, arising in non-cancerous tissues resulting from radiation treatment to a tumor of pelvic origin, are actually called as pelvic radiation disease. The incidence of pelvic radiation disease changes according to the radiation technique, the length of follow up, the assessmentmethod, the type and stage of cancer and several other variables. Notably, even with the most recent radiation techniques, i.e., intensity-modulated radiotherapy, the incidence of radiation-induced GI side effects is overall reduced but still not negligible. In addition, radiation-induced GI side effects can develop even after several decades; therefore, the improvement of patient life expectancy will unavoidably increase the risk of developing radiation-induced complications. Once developed, the management of pelvic radiation disease may be challenging. Therefore, the prevention of radiation-induced toxicity represents a reasonable way to avoid a dramatic drop of the quality of life of these patients. In the current manuscript we provide an updated and practical review on the best available evidences in the field of the prevention of pelvic radiation disease.

Pelvic radiation disease:Updates on treatment options

Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue,especially of distal large bowel,thus inducing gastrointestinal(GI) radiation-induced toxicity. Indeed,up to half of radiationtreated patients say that their quality of life is affected by GI symptoms(e.g.,rectal bleeding,diarrhoea). The constellation of GI symptoms- from transient to longterm,from mild to very severe- experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease(PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories,i.e.,medical and endoscopic. Of note,most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding(i.e.,causing chronic anemia) should firstly be considered for medical management(i.e.,sucralfate enemas,metronidazole and hyperbaric oxygen); in case of failure,endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute,transfusion requiring,bleeding. More well-performed,high quality studies should be performed,especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments.