Stress-induced Ulcers Research Articles

Dose-dependent protective effects of Lactobacillus rhamnosus GG against stress-induced ulcer.

Stress-related diseases are on the rise and stress is one of the common factors that lead to ulcer. Stress-induced mucosal bleeding is a serious complication observed in many critically ill patients. Due to the harmful side effects of proton pump inhibitors, natural and active alternative treatment methods for peptic ulcer treatment that are safe in terms of side effects are an urgent need for human health. We aimed to investigate the dose-dependent protective effects of Lactobacillus rhamnosus GG (LGG) against stress ulcer induced by cold restraint stress in rats. This study was performed in a total of 42 rats, in control group (C), stress group (S), pantoprazole (20 mg kg-1 day-1) group (P), LGG (3 × 108 cfu mL-1 day-1) + stress group (M1), LGG (15 × 108 mL-1 day-1) + stress group (M5) and LGG (30 × 108 mL-1 day-1) + stress group (M10) (each n = 7). Ulceration areas (mm2) were determined quantitatively with ImageJ software. Glucocorticoid, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by ELISA and malondialdehyde levels were determined by spectrophotometric measurement. Histopathological examinations were performed in gastric tissue. Therapeutic dose of LGG increased CAT, SOD and GPx levels; prevented excessive activation of the hypothalamic-pituitary-adrenal axis; reduced ulceration and bleeding in the gastric mucosal layer; and provided stabilization of mast cells. We can suggest that LGG may be beneficial for reducing the negative effects of stress on the body, for protecting against ulcer disease and for reducing or preventing the risk of stress-induced gastrointestinal bleeding in patients staying in intensive care units. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Toxicity study and ameliorative effects of the aqueous leaf extract of Lecanoidiscus cupanioides Planch (ex. Benth) on the stress-induced ulcer

Lecaniodiscus cupanioides Planch (ex. Benth) is effective in treating burns, fevers, and inflammatory conditions. This study investigates the toxicity effects of the aqueous leaf extract (ALE) of L. cupanioides and its effect on stress-induced ulcers in animal models. The plant was collected and a 1:30 (g/ml) plant powder/solvent ratio was extracted using an ultrasonic bath at 50 °C for 45 min. Up-and-down procedure was used for acute toxicity. During subacute toxicity testing, a total of 20 mice were divided into four groups of five animals each. While group 1 served as control, groups 2, 3, and 4 received 250, 500, and 1000 mg/kg of the extract daily for 21 days. On day 22nd, animals were sacrificed and samples were collected for hematology, biochemical, and histological analyses. In the stress-induced ulcer activity, male albino mice were randomly separated into 5 groups of 5 animals, treated with the test drug, and then dissected after being stressed using the water immersion model. LD50 was > 5000 mg/kg, and in biochemical examination, there was a significant decrease in the ALP level at medium and high doses (p value < 0.05) and non-significant alterations in the values of urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight and hematology parameters (p > 0.05). The histology results showed no evidence of liver and kidney toxicity. In conclusion, aqueous leaf extract of L. cupanioides was safe following a single dose (at 5000 mg/kg) and following repeated doses for 21 days (at 250, 500, and 1000 mg/kg). This study demonstrated that the extract had a significant effect on stress-induced ulcers at various dose levels when compared to the control (native, negative control, and omeprazole). The animals treated with 200mg/kg and 400mg/kg of the extract showed a significant increase in ulcer score, ulcer index, ulcer severity, and total acidity (p < 0.05). The ulcer protection ability of the aqueous plant extract was dose-dependent.

A comprehensive review on phytochemicals as potential therapeutic agents for stress-induced gastric ulcer

AbstractGastric ulcers are the most common chronic gastrointestinal tract disorders, marked by an inflamed break of the mucus membrane covering the alimentary tract. According to recent research, stress-induced ulcers are widespread in our society. A stress ulcer is a mucosal defect that may become complicated due to upper gastrointestinal tract bleeding. The underlying cause of this condition is pH. Physiological stress leads to severe sickness by triggering the excessive secretion of peptic juices or gastric acid. There is a never-ending quest for safe and affordable medication for this disorder. Nature offers many medicinal plants that can be used to treat a wide range of human ailments. Due to their relatively harmless and comparatively free of harmful effects, health-promoting features, pharmacological practices, and affordability to common people to regulate various diseases, medicinal plants, and herbal preparations are gaining a lot of interest in scientific communities these days. Many studies have recently been performed to classify extracts and their constituents that may have a therapeutic effect on peptic ulcers. Therefore, this review aims to address the molecular mechanisms and pharmacological effects of various phytochemicals related to stress-induced gastric ulcers. Combining phytochemical constituents with modern drugs and treatment methods can lead to the development of therapeutic drugs for gastric ulcers. Gastric ulcers and other related diseases may be treated permanently with this approach.

Proton Pump Inhibitors For HIV+ Patients - A Word Of Caution.

Madam, HIV (human immunodeficiency virus) is on the rise in Pakistan. A Lancet global health modeling study reports that patient registration with the National Aids Control Program (NACP) has risen from 4500 in 2013 to 24331 in 2019 [1]. In HIV+ patients, the gastrointestinal tract is a common site of infection, often leading to anorexia, dysphagia, vomiting, weight loss, and diarrhoea. A study conducted in 2016 showed that 80% of HIV-infected adults had moderate-severe GERD (gastro-oesophageal reflux disorder) symptoms [2]. Physicians often prescribe proton pump inhibitors (PPIs) to treat GERD and stomach or duodenal ulcers. This class of drugs is the most potent inhibitor of gastric acid secretion and is ,unfortunately, prescribed excessively and often inappropriately, regardless of if the patient is HIV+. A recent study shows that 66.2% of patients in a tertiary care hospital in Karachi, Pakistan receive PPIs without proper indication [3]. However, PPIs being prescribed inappropriately pose severe health risks to individuals that are HIV+. A recent study in 2019 raised the valid concern that the use of PPIs in patients already receiving anti-retroviral (ARV) therapy in HIV+ patients could very well be related to an increased risk of acute kidney infection (AKI) [4]. This is not the only research to show the adverse effect of PPI use in HIV patients. A 2017 study shows statistically significant increased innate immune activation due to the translocation of microbial products in HIV+ patients taking PPIs [5]. This can carry serious future implications for these patients post-treatment because higher levels of innate immune activation markers are associated with immunological failure in HIV-treated patients [6]. These statistics raise a very critical question- is it safe for PPIs to be prescribed so freely without any attention to patients being HIV+ or on ARV therapy? It is suggested that existing and future ARV therapies be planned carefully if PPIs are prescribed, and close attention be paid to a patient’s virologic response. In the case of acute hospital admission, where PPIs are prescribed for preventing stress-induced or GI ulcers, medication reconciliation algorithms that acknowledge the interaction between protease inhibitors (PIs) and PPIs should be used [7]. It would be prudent to use PPIs strictly when prescribed and for lesser periods of time.

Prevention of Psychological Stress Induced-Ulcer in rats Treated with Fruit Extract of Gymnospora montana

Gymnosporia montana (Roth) Bemth. is a traditional herbaceous plant of Celastraceous family found in different regions of India. We have earlier reported its antiulcer activity in aspirin-induced, pylorus-ligation induced, and cysteamine-induced ulcer models. As stress-induced ulcer amount to a majority of clinically evident ulcers, it was thought worthy to investigate the effects of the ethanolic extract of Gymnosporia montana in stress-induced ulcer paradigm. Psychological stress was produced by intra-species emotional communication in a jumping box. Rats were randomly divided into two groups; one was used as the ‘sender’ group that received electrical foot shocks of 10 s duration with 50 s intervallic current for the shock was increased stepwise from 10mA to 25mA. The animals showed emotional responses such as abnormal squealing and jumping. The other group called the ‘responder’ group were able to observe the ‘sender’ group mice but were not subjected to the shocks. A separate group of sender rats was used on each day. The receiver group was exposed to sender group for three consecutive days at the end of which, they were sacrificied and were observed for the presence of gastric lesions. Separate groups of rats were treated half an hour before with Ethanolic extract (500mg/kg, p.o.) and diazepam (5mg/kg, p.o.) and the protocol was repeated. At the end the ulcer index, pH of gastric contents and gastric volume was determined. Further, hisotopathology was also performed. Results revealed a good anti-ulcer activity which was comparable to that of diazepam. In conclusion, the present study affords a significant contribution in confirmation of the forklore effects of a traditional remedy.

Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial

BackgroundCritically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection.MethodsThe ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.DiscussionProphylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.Trial registrationREVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].

Antiulcer Effect of Aqueous Ethanolic Extracts of Pseudocedrela kotschyi (Schweinf) Harms (Meliaceae) and Ximenia americana L. (Olacaceae).

This study aimed to provide pharmacological evidence of Pseudocedrela kotschyi and Ximenia americana in preventing or healing peptic ulcers claimed by traditional healers in Burkina Faso. The trunk bark of Pseudocedrela kotschyi and the roots bark of Ximenia americana (Olacaceae) were macerated in mixed ethanol/water (80:20), respectively, to obtain dried extracts. Two models of hydrochloric acid (HCl, 0.3 M/ethanol, 60%) and hypothermic stress-induced peptic ulcer were used. The cytoprotective effect of individual or combined plant extracts was assessed at 1; 10; 30mg/kg. bw. Then, the healing effect of the extracts at 10mg/kg.bw was evaluated within 21 days of treatment on the hydrochloric acid-induced ulcer model. The extracts' antioxidant activity and phenolic content were assessed to support the plant extracts' efficiency. The extracts of P. kotschyi and X. americana at 10 mg/kg.bw reduced ulceration index in hydrochloric acid- and hypothermic stress-ulcer models by more than 83% and 65%, respectively. The extract from X. americana at 10mg/kg.bw allowed complete ulcer healing but not the association of the two plant extracts. The plant extracts had IC50of inhibition of DPPH radical lower than 5μg/mL and total ferric reducing antioxidant power of more than 77 mg EQAA/100mg. The total polyphenolic content was 64.82 ±0.99 and 53.75 ±1.39 mg EGA/g of dried extract of P. kotschyi and X. americana, respectively. X. americana extract is better than the combined two plant extracts in gastric cytoprotection and ulcer healing. Further investigations are needed to highlight mechanism-based effects.

Evaluation of gastroprotective and phytochemical properties of Terminalia superba engl. & diels (combretaceae) stem bark methanol extract

ABSTRACT Peptic ulcer is a disease that is affecting a large part of the population world-wide irrespective of the race and tribe. Advances made in the search for an ideal or perfect antiulcer drug has been eroded by cost, side effects and treatment failure. Search for cheap, safe, and effective drugs continues. It is the aim of the research to identify the secondary metabolites present in Terminalia superba Engl. & Diels (Combretaceae) stem bark methanol extract and investigate its gastroprotective properties. Methanol extract of T. superba was prepared by cold maceration extraction method using methanol. The extract was concentrated and subjected to acute toxicity test using Lorke’s method, and phytochemical investigation using standard methods. Gastro-protective activity was investigated by three models: aspirin- induced gastric ulcer, hypothermic restraint stress-induced ulcers and ethanol-induced gastric ulcer. The extract was safe in mice at doses below 2154 mg per Kg body weight and the extract contained the major secondary metabolites-alkaloids, flavonoids tannins, saponins, terpenoids, steroids. Pre-treatment with the extract reduced gastric ulceration in rats. There was a 77.3% reduction in the aspirin model, 75.2 % in the ethanol model and an 84 % in the Hypothermic restraint stress-induced ulcers model. There was a statistically significant difference at p= .05 between the treated groups and the un-treated group The methanol extract of Terminalia superba bark is rich in the major secondary metabolites and has gastro-protective a property.

Evaluation of Aqueous -Methanol Stem Bark Extract of Andira inermis for Peptic Ulcer-Protective Activity in Rats

Peptic ulcer disease is one of the commonest gastrointestinal diseases in the world and several orthodox drugs have been employed for the treatment of this disease. Although effective, some of these drugs produce adverse effects with a great tendency for the disease to reoccur. Hence, the need for further screening of medicinal plants for potential antiulcer activity and as sources for antiulcer lead compounds. Andira inermis is one of the plants identified to be used traditionally in ulcer-related conditions. This research work was aimed at evaluating the peptic ulcer-protective effects of aqueous-methanol stem bark extract of A. inermis in rats with acetylsalicylic acid and cold stress-induced ulceration. Adult Wistar rats were grouped into 5 of five rats each. Rats in Group A were administered normal saline (30 ml/kg i.p) to serve as the negative control. Rats in groups B, C and D were pretreated with the graded doses of the extract (100, 200 and 400 mg/kg i.p). Rats in group E were treated with Cimetidine (100 mg/kg i.p) to serve as the positive control group. Thirty minutes post-treatment, ulceration was induced with acetylsalicylic acid (150 mg/kg p.o) and all the rats were subjected to cold restrain stress for a 4h period. The rats were then sacrificed humanely and their stomachs were excised for gross examination and scoring of ulcer indices. The mean ulcer indices, percentage severity of ulceration and percentage ulcer protection were determined using corresponding calculations. The results revealed that acetylsalicylic acid combined with cold stress caused mostly marked congestion, gross erosions and deep ulcers with ecchymotic and petechial hemorrhages on the gastric mucosa of the rats treated with normal saline (30 ml/kg i.p.). The aqueous methanol stem bark extract of A. inermis significantly (p < 0.05) inhibited the formation of these lesions. The extract caused increased secretion of mucous on the gastric mucosa of rats and a dose-dependent reduction in ulcer indices. This was significant (p < 0.05) at the dose of 400 mg/kg i.p of the extract. The extract, at graded doses of 100, 200 and 400 mg/kg i.p produced percent ulcer protection of 60.0%, 73.3%, and 80.0% respectively. This was comparable to Cimetidine which showed a percent ulcer protection of 86.7%. This shows that the stem bark extract of Andira inermis possesses gastro-protective effects and has the potential to be developed as an agent for the treatment of peptic ulcers..

Modulation of lipid peroxidation and energy metabolism in the gastric mucosa as a mechanism ofantiulcer activity of placental cryoextract in the healing of stress-induced ulcers

Background. Peptic ulcer disease has a leading place in the overall structure of digestive diseases: its prevalence is 6.00–10.0% of the population in developed countries, and mortality ranges from 6 to 9.7 per 100 thousand population. An important etiological factor of this pathology is the neuropsychological background, primarily stress, which under repeated exposure becomes the initiating factor of physiological imbalance between the elements of aggression and protection of the gastric mucosa. The purpose was to establish the mechanisms of the protective activity of placental cryoextract based on the biochemical indicators of lipid peroxidation and antioxidant protection in the gastric mucosa on a model of stress-induced erosive-ulcerative damage. Materials and methods. Studies were performed on 28 nonlinear laboratory male rats weighing 200–220g. Stress-induced gastric ulcer was modeled under water-immobilization stress in rats according to the K.Y. Takagi etal. In the gastric mucosa, the content of reactants with thiobarbituric acid was determined spectrophotometrically by the method of T. Asakawa etal., catalase activity— spectrophotometrically by the method of M.A.Korolyuk etal., the content of reduced glutathione— spectrophotometrically by the method of E.D. Beutler etal., the level of adenyl nucleotides was determined using chromatographic method. Energy charge was calculated by D.E. Atkinson equation. Results.The prophylactic five-day use of placental cryoextract led to a decrease in the severity of stress-induced lipid peroxidation and energy imbalance in the gastric mucosa. Thus, it was found that rats who received placental cryoextract had a statistically significant (p<0.001) increase in adenosine triphosphate content by 73.3%, an increase in adenosine diphosphate (p<0.001) by 37.3% and a decrease in adenosine monophosphate (p<0.001) by 47.6% that led to an increase in energy charge (p<0.001) by 35.1% compared to rats exposed to water-immobilization stress without correction (control group). It was shown that the use of placental cryoextract led to a statistically significant (p<0.001) increase in the antioxidant-prooxidant index by 3.1 times versus control group, which was (26.60±0.96) and (8.60±0.43), respectively. Conclusions. Prophylactic five-day administration of placental cryoextract leads to the restoration of balance in the system of adenyl nucleotides and, accordingly, to a statistically significant (p<0.001) increase in the energy charge by 35.1% compared to the control animals. Inhibition of stress-induced hyperactivation of lipid peroxidation in the gastric mucosa is one of the mechanisms of its antiulcer activity.

Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials.

Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications. We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30-0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23-0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26-1.06; p = 0.07; I2 = 0%). In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.

Involvement of microRNA/cystine/glutamate transporter in cold-stressed gastric mucosa injury.

Stress ulcers are complicated by severe trauma and other critical diseases, the mechanism of which remains unclear. An increasing number of studies have shown that microRNAs (miRNAs) are important regulators of stress responses such as hypoxia, abnormal temperature, and inflammation. The evidence indicates that miRNAs are also involved in regulating stress-induced ulcers. Recently, we demonstrated that gastric mucosal injury induced by aspirin is related to the reduction of glutamate levels by inhibition of cystine/glutamate transporter (xCT) activity. In the present study, the effect of a miRNA/xCT on gastric mucosal injury induced by cold stimulation was investigated. We found that cold stimulation induced gastric mucosa injury with a reduction in glutamate levels and xCT activity and upregulation of miR-143, miR-152, and miR-181 expression. Exogenous glutamate significantly alleviated gastric mucosa injury by cold stimulation. In vitro experiments demonstrated that treatment with miR-143, miR-152, or miR-181 mimics directly induced cell damage. The effects of these mimics were alleviated by exogenous glutamate. The present study suggests that miR-143, miR-152, and miR-181 are involved in cold stimulation-induced acute gastric mucosal injury. Furthermore, the regulatory effect of miRNAs on gastric mucosa injury induced by cold stimulation is related to a decrease in glutamate release by reduction of cystine/glutamate transporter activity.

Gastroprotective potential of Annona senegalensis ethanol leaf extract in Wistar rats

The leaves of Annona senegalensis are traditionally used for the treatment of different diseases in Nigeria, including gastrointestinal disorders. The anti-diarrheal and ulcer-protective activities of its ethanol extract were determined in Wistar rats. This extract was investigated for castor oil-induced diarrhoea, intestinal transit time and castor oil-induced enteropooling in rats. The leaf extract was also tested for its ulcer protective potentials in acetylsalicylic acid, ethanol and stress-induced ulceration in rats. The phytoconstituents and oral acute toxicity of the leaf extract were also assessed. The extract significantly reduced the frequency of faecal dropping in castor oil-induced diarrhoea. It also inhibited the masses and volumes of intestinal accumulation in castor oil-induced enterpolling in rats. The distance travelled by charcoal meal was as well reduced. The phytochemical tests revealed the presence of alkaloids, saponins, tannins, flavonoids, terpenoids, and anthraquinone. However, the LD50 was greater than 5000 mg/kg in rats. The ethanol leaf extract of A. senegalensis exhibited strong antidiarrheal and ulcer protective activities, thus justifying its folkloric use by the local population against gastrointestinal disorders.

Possible cytoprotective mechanisms of oxytocin against 5-fluorouracil-induced gastrointestinal mucositis.

Gastrointestinal mucositis is a common and dose-limiting side effect characterized by ulcerative lesions in the mucosa of the digestive tract in patients receiving anticancer drugs such as 5-fluorouracil (5-FU), a potent antineoplastic drug. Several protocols have reported the efficacy of therapeutic interventions to prevent this side effect, although complete success has not yet been achieved and mucositis remains one of the most serious complications associated with 5-FU therapy. Oxytocin, a well-known antistress agent, has been reported to have comparable effects to ranitidine. Previous studies have shown that oxytocin inhibits gastric acid secretion and the expression of proinflammatory cytokines in rats. If oxytocin can reduce stress-induced ulcers via antioxidant, antiapoptotic, and anti-inflammatory pathways, then it may have a dose-dependent effect on gastrointestinal mucositis caused by 5-FU.

Fluvoxamine Suppressed Oxidative Stress associated with Tissue Erosion

Centrally-acting drugs have been increasingly used for gastrointestinal diseases, such as opioids used for diarrhea and phenothiazine as antiemetic agents. Recent reports focused on the identification of the efficacy of these drugs in peptic ulcer protection; by tackling the oxidative stress associated with the inflammatory reaction of ulceration. The present study aimed to identify the differences between fluoxetine versus fluvoxamine in terms of antioxidant activity. To do so, an animal model of stress-induced ulcer was utilized by exposing rats to high doses of indomethacin and these rats were sub-classified into four groups (control, fluoxetine, fluvoxamine, and misoprostol) for comparison. Blood samples were collected from the studied groups and analyzed by measuring plasma levels of total antioxidant and malondialdehyde (MDA). The results confirmed that fluvoxamine possesses an antioxidant activity that is comparable to misoprostol and significantly higher than that of fluoxetine effects; the latter showed a non-significant effect in ordinary doses. In conclusion, these findings might provide a clue for future directions for the discovery of new antiulcer agents through structural modification of the newly introduced antidepressant agents in clinical use.

Melatonin rescues swim stress induced gastric ulceration by inhibiting matrix metalloproteinase-3 via down-regulation of inflammatory signaling cascade

AimThis study investigated the link between forced swim induced acute gastric ulceration, inflammation and MMP-3 along with the possible mechanism of protective efficacy of melatonin. Main methodsWe distributed Balb/c mice into four different groups. Group 1 and 2 were given PBS gavage. Group 3 and 4 were given melatonin (60 mg/kg b.wt.) and omeprazole (25 mg/kg b.wt.), respectively, an hour prior to forced swim. Ulcer index, tissue histology, immunohistochemistry, protein carbonylation, lipid peroxidation, Myeloperoxidase, Zymography, Western blotting, reactive oxygen species (ROS), mitochondrial dehydrogenase, mitochondrial transmembrane potential and bioinformatical analysis were performed. Key findingsOur data revealed that gastric ulceration due to forced swim stress is responsible for overproduction of ROS, which may be a prime reason for mitochondrial dysfunction and induction of apoptosis via activation of Caspase-3. ROS is also responsible for p38 phosphorylation which in turn increases the activity of MMP-3 in ulcerated milieu, along with the oxidation of proteins, peroxidation of lipids and altered expression patterns of heat shock protein (HSP)-70. Melatonin is shown to reduce the inflammatory burden in gastric milieu and offers gastroprotection by binding to the active site of MMP-3; thereby inhibiting its activity, as suggested by in silico studies. Melatonin also inhibits the downregulation of HSP-70 and activates p38 dephosphorylation and thereby, it rescues gastric mucosal cells from stress-induced ulceration. SignificanceOur findings suggest that, melatonin imparts its gastroprotective effect by down-regulating the activation of MAPK-ERK pathway along with binding to the active site of MMP-3.

Gastroprotective effect of Phyllanthus reticulatus Poir. against pylorus ligation-, ethanol-induced, and stress-induced ulcer models in Wistar rats

Gastroprotective effect of Phyllanthus reticulatus Poir. against pylorus ligation-, ethanol-induced, and stress-induced ulcer models in Wistar rats

Comparative study on the possible protective effect of boswellic acids and/or co-enzyme Q10 against stress-induced peptic ulcer in normally fed and protein malnourished rats

Comparative study on the possible protective effect of boswellic acids and/or co-enzyme Q10 against stress-induced peptic ulcer in normally fed and protein malnourished rats

EVALUATION OF GASTROPROTECTIVE EFFECTS OF METHANOL EXTRACT OF TEPHROSIA VILLOSA AGAINST EXPERIMENTALLY INDUCED ULCERS IN WISTAR RATS

Objective: The present research work was designed to investigate the gastroprotective potentials of methanol extract of Tephrosia villosa. Methods: The aerial parts of Tephrosia villosa were dried under shade, powdered and deffated with petroleum ether and then marc leftover was subjected to methanol extraction using soxhlet apparatus using soxh-let apparatus. Antiulcer activity of methanol extract was determined against stress-induced and aspirin-induced ulcers in experimental animal models. The total number of ulcers formed, ulcer index, percentage inhibition, ulcerated area, protected area, pH and Total acidity were parameters in the study. Results: Methanol extract of Tephrosia villosa at medium (200 mg/kg) and high (200 mg/kg) could significantly (P&lt;0.01) reduced the total number of ulcers formed, ulcer index, ulcerated area and total acidity in therapeutic groups compared to vehicle control and thereby significantly (P&lt;0.01) increased percentage inhibition of ulcers and protected area which was evident by the significant rise in pH of gastric content. The effect of extracts was dose-dependent and results were comparable to that of standard drug omeprazole. Conclusion: The results obtained from the present work suggest that the methanol extract of Tephrosia villosa possess significant anti-ulcer potentials against experimentally induced ulcers in albino rats.

Gastroprotective effects of hydrogen sulfide, carbon monoxide and nitric oxide on an experimental ulcer model in rats

Background/Aim: Gastric mucosal injury induced by several agents such as ethanol, stress or nonsteroidal anti-inflammatory drugs (NSAIDs) is a common severe disorder. Hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) are gaseous autacoids that are endogenously produced in mammalian tissues. Recently, several studies confirmed that H2S, CO and NO play a role in gastroprotection. Our work aimed to evaluate and compared the gastroprotective effects of H2S, CO and NO on ethanol-, indomethacin- and stress-induced rat ulcer models. Methods: The effects of NaHS (5 mg/kg), CORM-2 (5 mg/kg) and L-arginine (100 mg/kg) were investigated on gastric ulcer models induced by ethanol (1 ml 96% i.g.), stress (cold+immobility) and indomethacin (40 mg/kg i.g.). The ulcer index, gastric mucus secretion, free and total acidity, and levels of TNF-α, PGE2, MDA GSH, COX-1, COX-2 were measured. Results: NaHS and CORM-2 decreased the increased TNF-α and MDA levels in ethanol-induced ulcer. L-arginine reduced mucin secretion, TNF-α and GSH levels in stress-induced gastric ulcer. Conclusion: The present study showed that H2S and CO may have gastroprotective activity against ethanol-induced ulcers and NO may be gastroprotective against stress-induced ulcers.