Gastric Malondialdehyde Research Articles

Gastroprotective mechanism of Talinum triangulare on ethanol-induced gastric ulcer in Wistar rats via inflammatory, antioxidant, and H+/K+-ATPase inhibition-mediated pathways

The increase in the incidence of gastric ulcer (GU) has posed major threat on public health. This research aimed to evaluate gastroprotective properties of the aqueous leaf extract of Talium triangulare (AETT) in ethanol-induced gastric ulceration. GU was induced via oral administration of single dose of 5 mLkg−1 of 90% ethanol in rats and protection of 200 mgkg−1 bw of AETT and 20 mgkg−1 bw of omeprazole was investigated for 14 d via oral treatment. Influence of AETT on anti-inflammatory, redox assays, ulcer index (UI), and gastric mucosa histological alterations were evaluated. Significant increase in myeloperoxidase (MPO) and tumor necrosis factor-alpha levels compared to untreated group established gastric inflammation in rats induced by ethanol. Gastric ulcerated group exhibited heightened oxidative stress with concurrent decline in activities of antioxidant enzymes. Ethanol exposure to rats resulted in induction of lipid peroxidation, prominently elevating gastric malondialdehyde (MDA) concentration. Nevertheless, treatment with AETT or omeprazole exhibited substantial anti-inflammatory effects within gastric mucosa by attenuating expression of markers associated with inflammation. AETT demonstrated reduction in concentrations of MDA and H2O2, thereby alleviating progression of lipid peroxidation cascades. Also, AETT exhibited mitigating effect on ethanol-induced oxidative harm by enhancing the functionality of protective enzymes and elevating glutathione (GSH) concentration. Overall, AETT exhibited enhancements in activities of cytoprotective antioxidant enzymes, mitigated impact of oxidative stress and inflammation, inhibited lipid peroxidation, and decreased UI score. These beneficial effects could be attributed to phytochemicals present in AETT including 6,10,14-trimethyl-2-pentadecanone and Phytol. Outcome of this study established the traditional herbal claims of AETT.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway

BackgroundGastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved.MethodsAn ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done.ResultsThe ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group.ConclusionsAloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation

(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers.

Piper sarmentosum Roxb. methanolic extract prevents stress-induced gastric ulcer by modulating oxidative stress and inflammation.

This study investigated the gastroprotective effect of Piper sarmentosum (PS) on stress-induced gastric ulcers in rats by measuring its effect on oxidative stress, gastric mucosal nitric oxide (NO), and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly divided into four groups; two control groups (non-stress and stress) and two treated groups supplemented with either methanolic PS extract (500mg/kg body weight) or omeprazole (OMZ; 20mg/kg) orally. After 28days of treatment, the stress control, PS, and OMZ groups were subjected to water-immersion restrain stress (WIRS) for 3.5h. Gastric tissue malondialdehyde (MDA), NO, superoxide dismutase (SOD), inducible NO synthase (iNOS), SOD mRNA, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. WIRS significantly increased gastric MDA, NO, and pro-inflammatory cytokine levels compared to the non-stressed control group. PS and omeprazole supplementation significantly reduced WIRS-exposure-induced gastric ulcers and MDA, iNOS, and IL-1β levels. However, only PS reduced NO, TNF-α, and IL-6 levels, which were upregulated in this ulcer model. In conclusion, the gastroprotection afforded by PS is possibly mediated by gastric mucosal NO normalization through reduced iNOS expression and attenuation of inflammatory cytokines. PS showed a greater protective effect than omeprazole in reducing gastric lesions and NO, TNF-α, and IL-6 levels, and iNOS expression.

Gastroprotective activity of yogurt fortified with purple roselle extract in rats exposed with 2,3,7,8-TCDD

Persistent organic pollutant 2,3,7,8-Tetrachlorodiobenzo-p-dioxin (TCDD), known as harmful congeners of dioxin, has many adverse effects on human or animal health. This TCDD enters the body through inhalation, ingestion, and skin contact. Purple Roselle is a well-known herb-medicinal plant having antioxidant properties. This study aimed to evaluate the antioxidant capacity of purple roselle water extract along yogurt against dioxin exposure. The antioxidant properties of the extract were measured by malondialdehyde (MDA) levels and gastrointestinal histology. For this, 25 white male rats (Rattus norvegicus) were used, and these rats were divided into five groups negative control, positive control (TCDD 200 ng/kg BW), and three treatment groups (TCDD 200 ng/kg BW + yogurt fortified with purple roselle water extract concentrations 0.5, 1, and 1.5 percent), all the treatments were given orally. Gastric MDA was determined quantitatively using the Thiobarbituric Acid (TBA) method and the one-way ANOVA test, continued by a Tukey post hoc test with a confidence level of 95% while the gastric histology was observed descriptively. Results of the study revealed that supplementation of fortified yogurt with 1% purple roselle extract could dramatically reduce MDA levels (p<0,05) and heal histological damage in the lamina propria mucosa of stomach rats subjected to TCDD. Results of the study can be concluded that consuming yogurt with purple roselle extract can reduce MDA levels and repair histological damage to the gastric mucosa caused by dioxin exposure.

Lactoferrin mitigates ethanol-induced gastric ulcer via modulation of ROS/ICAM-1/Nrf2 signaling pathway in Wistar rats.

We aimed to investigate the gastroprotective effect of lactoferrin (LF; 100 & 300 mg/kg) in male Wistar rats versus gastric ulcers induced by 96% ethanol. Rats were randomly allocated into 4 groups: control, ethanol, ethanol+LF100, and ethanol+LF300. LF100 & 300 were given 15 days before ulcer induction. At the end of the experiment, the gastric mucosa was examined macroscopically and microscopically. The ethanol group showed damage and degeneration of the stomach mucosa in addition to elevation of oxidative and inflammatory biomarkers. LF showed explicit healing of the gastric mucosal damage. LF reduced gastric malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), and intracellular adhesion molecule-1 (ICAM-1). On the other hand, LF elevated the depleted reduced glutathione (GSH) and Nuclear factor-erythroid factor 2 (Nrf2). Our current study is the first to study the antiulcer effect of LF via its potential modulatory effects on the ROS/ICAM-1/Nrf2 signaling pathway. Moreover, we concluded that pretreatment with LF100 & 300 mitigated the ethanol-induced gastric ulcer via modulation of both oxidative stress and inflammatory responses.

Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury

ABSTRACT Objectives: This study investigated the impact of rohypnol on gastric tissue integrity. Methods: Forty male Wistar rats were randomized into control, low dose rohypnol-treated, high dose rohypnol-treated, low dose rohypnol-treated recovery and high dose rohypnol-treated recovery groups. Results: Rohypnol caused significant rise in gastric malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), tumour necrotic factor-α (TNF-α), and interleukin-6 (IL-6) levels. Also, rohypnol caused reductions in gastric reduced glutathione (GSH) (as well as GSH/GSSG), and activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), cyclo-oxygenase (COX-2). Furthermore, rohypnol upregulated caspase 3 activity and induced gastric DNA damage, evident by a rise in 8-hydroxydeoxyguanosine (8-OHdG) and DNA fragmentation index (DFI) in gastric tissue. These alterations were coupled with reduced gastric weight and distorted gastric cytoarchitecture. Cessation of rohypnol caused a significant but not complete reversal of rohypnol-induced gastric damage. Conclusion: This study revealed that rohypnol induced gastric injury by suppressing glutathione content and COX-2 activity, and upregulating caspase 3-dependent apoptosis, which was partly reversed by rohypnol withdrawal.

The Effects of Isolate of Goat Casein Yoghurt Milk to MDA Level and Gastric Histopathology of Rats Exposed to 2,3,7,8-Tetrachlorinedibenzo-P-Dioxin (TCDD)

Dioxins are toxic compounds belonging to organochlorine compounds are highly reactive and produce free radicals that can damage stomach cells. 2,3,7,8-Tetrachlorinedibenzo-p-dioxin (TCDD) is the type of dioxin that has the highest toxicity. Casein goat milk yogurt has the potential as an antioxidant. This study aims to determine the preventive effect of goat milk yoghurt on exposure to dioxin observed levels of malondialdehyde (MDA) and gastric histopathology. Experimental research using Completely Randomized Design (RAL). The white rats (Rattusnorvegicus) were divided into 6 groups, the normal group, casein control (goat milk yoghurt dose 600 mg / kg BW), positive control (TCDD dose 100 ng / kg BW), treatment 1 (goat milk yoghurt 300 mg / kg BW and TCDD 100 ng / kg BW), treatment 2 (goat milk yoghurt 600 mg / kg BW and TCDD 100 ng / kg BW), and treatment 3 (goat milk yoghurt 900 mg / kg BW and TCDD 100 ng / kg BW). Gastric MDA levels were measured using the Thiobarbituric Acid (TBA) assay method with 530 nm wavelength UV-Vis spectrophotometric measurement and gastric histopathology using Hematoxylin-Eosin (HE) staining observed in the form of gastric mucosal cell damage. Gastric MDA levels were analyzed using one way ANOVA statistical test, α = 5% and gastric histopathology analysis were descriptively processed. The results showed that goat milk yoghurt with dose of 600 and 900 mg / kgBW was the best dose in preventing the increase of MDA level of gastric from white rat (Rattusnorvegicus) exposed TCDD significantly (p <0,01), and dose 900mg / kgBB prevented erosion of gastric mucosal cells. The conclusion of this research is giving goat milk goat yoghurt able to prevent the increase of MDA level and erosion of gastric mucosal cells caused by TCDD.

Gastroprotective Effects of Betanin Against Ethanol-induced Gastric Ulcer in Rats

BackgroundBetanin is the principal pigment and active phytochemical constituent of beetroot. The protective roles of betanin are documented in the heart, kidney, liver, and lung, but its potential gastroprotective effect is not assessed thus far. A number of studies demonstrated that betanin could inhibit lipid peroxidation.ObjectivesThe current study aimed at investigating the gastroprotective effect of betanin in gastric ulcer induced by ethanol.MethodsIn the present study, a group of animals were treated with betanin (50, 100, and 200 mg/kg, orally) and the other group received ranitidine as a reference antiulcer agent. One hour later, the gastric mucosal ulceration was induced by oral administration of absolute ethanol and the rats were sacrificed one hour. The gastric ulcers were assessed by macroscopic and histopathological examinations. Also, gastric malondialdehyde (MDA) level and nitric oxide (NO) content were measured.ResultsOral administration of betanin 100 and 200 mg/kg of body weight prior to receiving ethanol significantly attenuated the number and length of gastric ulcers as compared to the ethanol group. Moreover, pretreatment with betanin could significantly decrease stomach MDA level and maintain stomach NO content similar to that of the control group. Histopathological examinations indicated that ethanol-induced gastric ulcer was attenuated by betanin and no significant difference was observed between the betanin (200 mg/kg) and ranitidine groups.ConclusionsThe findings indicated that betanin has gastroprotective effects on gastric ulcers, which could be related to attenuated lipid peroxidation and reestablished gastric NO content.

Methylene Blue Protects against Acidified Sodium Taurocholate-Induced Gastric Mucosal Damage

The effect of methylene blue (MethyB) on the development of gastric mucosal injury caused by orally given acidified sodium taurocholate (80 mM in 2 ml of 0.15 N HCI) in pylorus-ligated rats was studied. MethyB was intraperitoneally given at doses of 20 and 40 mg/kg at time of pylorus-ligation, and animals were euthanized 90 min later, when gastric secretory responses and the number and severity of mucosal lesions were determined. Lipid peroxidation (malondialdehyde), nitric oxide, reduced glutathione (GSH), and paraoxonase-1 (PON-1) activity in gastric homogenates were measured. Gastric mucosal histopathology and histochemical staining for mucopolysaccharides were also done. Results indicated that acidified sodium taurocholate (Na+-taurocholate) caused severe gastric lesions. It also increased gastric malondialdehyde by 70% and decreased GSH levels by 36.4% compared with the corresponding control values. Additionally, nitric oxide decreased by 49.3% and PON-1 activity fell by 54.2% in gastric tissue of Na+-taurocholate-treated rats. The administration of MethyB reduced the number and severity of gastric mucosal lesions but had no effect on gastric acid secretion in Na+-taurocholate-treated rats. MethyB resulted in decreased malondialdehyde and increased GSH, nitric oxide, and PON-1 activity in a dose-dependent manner. Na+-taurocholate caused massive sloughing and hemorrhagic erosions of the superficial parts of gastric epithelium, lamina propria, and sloughing of gastric glands. These changes were markedly attenuated by MethyB at 40 mg/kg. MethyB also restored gastric mucus as indicated by the increase in apical epithelial cells positively stained with periodic acid Schiff. These data suggest a protective effect for MethyB against gastric mucosal damage caused by Na+-taurocholate which is likely to be due to decreased oxidative stress.

Apoptosis as a mechanism for burn-induced gastric mucosal injury

ABSTRACT Introduction: Severe thermal burns disturb tissue homeostasis of many organs, but the exact mechanisms of gastric mucosa changes are not yet clear. Various cellular mechanisms, such as cell activation, mitochondrial dysfunction, free oxygen radicals and cytokine overproduction may be involved in this process. Aim: The aim of this study was to assess the levels of malondialdehyde (MDA), apoptotic proteins Bax and Bcl-2 in normal gastric mucosa and to test the hypothesis that oxidative stress activation induces apoptotic processes in the stomach after experimental thermal trauma. Materials and M ethods: Under anesthesia, the shaved rats` dorsum was exposed to 90° C bath for 10 s to induce third-degree burn injury, involving 30% of the total body surface area. We determined the tissue level of MDA, a lipid peroxidation marker, by spectrophotometric method and the apoptosis of epithelial cells in gastric mucosa, which was immunohistochemically determined at the level of Bcl-2 and Bax in burn trauma. Results: The gastric MDA level was higher (p<0.01) in the burned group compared to the control group 24 hours after thermal injury. The gastric mucosa in the treated group showed congestion, degenerative changes in the surface epithelium, focal destruction of glandular epithelium with formation of acute erosions. Bax expressed moderately in epithelial cells, predominantly in the basal parts of the gastric glands, while in the control group protein content was localized in the same region, but it was weak. Bcl-2 protein in the control group revealed nuclear expression in surface epithelium, while in the basal layer of gastric mucosa the expression was moderate and mainly cytoplasmic. In the burned group, Bcl-2 expression was more diffuse, nuclear and cytoplasmic, but cytoplasmic expression was weak. C onclusion : Thermal skin trauma induces gastric mucosal injury through the activation of lipid peroxidation, increase of pro-apoptotic Bax protein expression and decrease of anti-apoptotic Bcl-2 protein expression in epithelial cells. We suggest that apoptosis is a possible mechanism for structural changes in the gastric mucosa.

Gastric Mucosal Oxidative Stress Markers in Children with Helicobacter Pylori Infection

'Helicobacter pylori' "H. pylori" is one of the most common infections that colonizes human gastric mucosa and generates reactive oxygen and nitrogen species. The aim of this study was to evaluate the oxidative stress markers in the gastric mucosa of "H. pylori"- infected children. The present study was carried out on 60 children infected with "H. pylori" including 28 males, 32 females with their age ranging from 7-10 years and mean age value of 8.5 ± 1.65 years (Group I). This study included also 60 healthy children as a control group including 26 males and 34 females with their age ranging from 7-11 years and mean age value of 8.99 ± 1.63 years (Group II). All children were subjected to full history taking, thorough clinical examination, diagnosis of "H. pylori" infection through "H. pylori" stool antigen testing using enzyme immunoassay kit (Group I and II) and gastric antrum mucosal biopsies which were tested for urease activity using Campylobacter like organism test (CLO test) (Group I only) and measurement of gastric mucosal oxidative stress markers including Malondialdehyde (MDA), Superoxide dismutase (SOD), reduced glutathione (GSH), Catalase and nitric oxide (NO) [The sum of Nitrite (NO2 -) and Nitrate (NO3 -)]. The main clinical presentations in studied patients and controls were recurrent abdominal pain, recurrent vomiting, dyspepsia and hematemesis with no significant difference between patients and controls as regard abdominal pain, vomiting or dyspepsia but hematemesis was found only in patients. There were significant differences between patients and controls as regard site and duration of abdominal pain with epigastrium being the most common site of pain in patients versus diffuse abdominal pain in control group with significantly longer duration of abdominal pain in patients compared with controls. "H. pylori" infected children has significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, catalase and SOD compared to controls (nitric oxide was 85.68 ± 23.16 nmol/gm in patients versus 106.423±2.111 nmol/gm in controls, reduced glutathione in patients was 1.83 ± 0.16 nmol/gm versus 2.44 ± 0.07 nmol/gm in controls, MDA in patients was 189.15 ± 6.14 nmol/gm versus 166.21 ± 3.13 nmol/gm in controls, catalase was 57.38 ± 19.85 unit/gm in patients versus 36.51 ± 2.34 unit/gm in controls and SOD in patients was 375.52 ± 26.51 unit/gm versus 318.51 ± 32.06 unit/gm in controls. "H. pylori" infection is associated with gastric mucosal oxidative stress with significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, Catalase and SOD in patients compared to controls. Antioxidants may be an important adjuvant therapy for "H. pylori" infection as this infection is associated with gastric mucosal oxidative stress.

The effect of 1,25 dihydroxyvitamin D3 on HCl/Ethanol-induced gastric injury in rats.

This study evaluated ulceroprotective and antioxidant effect of 1,25 dihydroxyvitamin D3 against gastric damage in rats. Rats were treated intraperitoneally with either 1,25 dihydroxyvitamin D3 (0.25 μg/kg) or saline for 14 days. On day-15, the non-selective cyclooxygenase inhibitor indomethacin (10 mg/kg; subcutaneously), the inhibitor of sulfhydryl groups N-ethylmaleimide (10 mg/kg; intraperitoneally) or ATP-sensitive K+ channel blocker glibenclamide (10 mg/kg; orally) was given prior to 1,25 dihydroxyvitamin D3. Animals were euthanized at 60 min post ulcerogenic challenge (0.3 M HCl and 60% ethanol (0.2 mL; orally). Stomach and blood were collected for biochemical and histological evaluations. HCl/Ethanol group revealed severely damaged mucous and glandular epithelium with diffuse hemorrhage and inflammatory cell infiltration (microscopic score: 10.67 ± 0.67 and ulcer index: 33.13 ± 5.09). 1,25 dihydroxyvitamin D3 decreased the extent of damage (microscopic score: 6.80 ± 0.02 and ulcer index: 19.00 ± 4.34; p < 0.05), and the elevations in gastric malondialdehyde level (p < 0.001), myeloperoxidase activity (p < 0.001), nuclear factor-κB expression (p < 0.05), and apoptotic index (p < 0.05) following HCl/Ethanol challenge. Decreased gastric glutathione following HCl/Ethanol administration was restored by 1,25 dihydroxyvitamin D3 (p < 0.01). These findings demonstrated protection of the gastric mucosa against HCl/Ethanol-induced injury by 1,25 dihydroxyvitamin D3 via attenuation of inflammatory reaction, oxidative stress and apoptosis.

Levels of malondialdehyde in the gastric juice: Its association with Helicobacter pylori infection and stomach diseases.

Helicobacter pylori (H.pylori) infection causes elevation of lipid peroxidation product malondialdehyde (MDA) and this association may be due to the bacterium causing reactive oxygen species-mediated damage to DNA in the gastric epithelium. The aim of this study was to investigate the gastric juice MDA levels in relation to H.pylori infection and associated gastric diseases. Gastric juice samples were obtained from 117 patients undergoing endoscopy, and gastric juice MDA levels were determined by high-performance liquid chromatography (HPLC) system. We compared the MDA levels between patients with and without H.pylori infection and assessed the differences of MDA levels between chronic gastritis, gastric intestinal metaplasia, and gastric cancer postsurgical resection. Malondialdehyde levels in gastric juice were significantly higher in chronic gastritis patients with H.pylori infection than in those without H.pylori infection (P<.0001). In patients without H.pylori infection, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection had significantly higher gastric juice MDA level than patients with chronic gastritis. As a whole, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection also had significantly higher MDA levels in gastric juice as compared to patients with chronic gastritis (P<.01). However, the difference of gastric juice MDA levels between gastric intestinal metaplasia and gastric cancer postsurgical resection was not significant. Malondialdehyde in gastric juice could be used as a potential diagnostic biomarker for H.pylori infection and associated gastric diseases. The gastric juice MDA levels increased proportionally with the severity of gastric diseases.

THE EFFECT OF MELATONIN AGAINST GASTRIC OXIDATIVE STRESS AND DYSLIPIDEMIA IN STREPTOZOTOCIN-INDUCED DIABETIC RATS.

The aim of this study was to evaluate the possible protective effects of MT against gastric oxidative stress and dyslipidemia in streptozotocin (STZ) - induced diabetic rats. Forty male Wistar rats were randomly divided into five groups: control, diabetic, MT 5 mg/kg+ STZ, MT 10 mg/kg+ STZ and MT 20 mg/kg+ STZ. STZ (60 mg/kg) was intraperitoneally (ip) injected as a single dose for diabetes induction. One week after STZ administration, MT was injected daily as ip for 14 days. The levels of malondialdehyde (MDA), total thiol and glutathione, as well as superoxide dismutase (SOD) and catalase activities were measured in gastric tissue. Serum concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were also determined. Serum glucose significantly increased in diabetic group compared to control group. STZ induced a significant decrease in gastric tissue levels of total thiol, glutathione, catalase and SOD activities and a significant increase in MDA concentration. In diabetic rats, serum TG, LDL and TC were significantly higher and HDL was significantly lower than in the control group. Treatment of diabetic rats with MT caused a significant increase in gastric total thiol content and glutathione concentration as well as SOD and catalase activities. Gastric MDA concentration and serum LDL, TG and TC were significantly lower in MT-treated groups when compared with diabetic group. These data suggested that MT has a therapeutic effect on gastric oxidative damage and dyslipidemia induced by diabetes that possibly may be due to its antioxidant effects.

Lipoic acid protects gastric mucosa from ethanol-induced injury in rat through a mechanism involving aldehyde dehydrogenase 2 activation

Numerous studies demonstrate that reactive aldehydes are highly toxic and aldehyde dehydrogenase 2 (ALDH2)-mediated detoxification of reactive aldehydes is thought as an endogenous protective mechanism against reactive aldehydes-induced cell injury. This study aims to explore whether lipoic acid, a potential ALDH2 activator, is able to protect gastric mucosa from ethanol-induced injury through a mechanism involving clearance of reactive aldehydes. The rats received 60% of acidified ethanol through intragastric administration and held for 1h to establish a mucosal injury model. Lipoic acid (10 or 30mg/kg) or Alda-1 (a positive control, 10mg/kg) was given 45min before the ethanol treatment. The gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) contents, and ALDH2 activity. The results showed that acute administration of ethanol led to an increase in gastric ulcer index, cellular apoptosis, 4-HNE and MDA contents concomitant with a decrease in ALDH2 activity; these phenomena were reversed by lipoic acid or Alda-1. The gastric protection of lipoic acid was attenuated in the presence of ALDH2 inhibitor. Based on these observations, we conclude that lipoic acid exerts the beneficial effects on ethanol-induced injury through a mechanism involving, at least in part, ALDH2 activation. As a dietary supplement or a medicine already in some countries, lipoic acid can be used to treat the ethanol - induced gastric mucosal injury.

Syzygium aromaticum water extract attenuates ethanol‑induced gastric injury through antioxidant effects in rats.

The aim of the present study was to investigate whether Syzygiumaromaticum water extract (SAWE) has a protective effect against ethanol‑induced gastric injury in rats. Acute gastric injury was induced via intragastric administration of absolute ethanol at a dose of 5ml/kg. SAWE (250or500mg/kg/day) or cimetidine (100mg/kg/day), which was used as a positive control, were administered to the rats 2h prior to ethanol administration for 3days. All rats were sacrificed 24h following the final ethanol administration. To examine whether SAWE has a gastroprotective effect, assays were performed to assess the contents of malondialdehyde (MDA) and glutathione (GSH), the activities of catalase, glutathione‑S‑transferase and superoxide dismutase, and an immune-linked immunosorbent assay was performed for prostaglandin E2 (PGE2) production in gastric tissues by hematoxylin and eosin and periodic acid-Schiff staining. Histological assessment of the gastric wall was performed. Compared with ethanol treatment alone, treatment with SAWE at a dose of 250mg/kg/day significantly decreased the gastric MDA content and increased the GSH content, catalase activity, and production of gastric PGE2. Histological assessment showed that SAWE attenuated inflammatory cell infiltration and the loss of epithelial cells. These findings suggested that SAWE protected against ethanol‑induced gastric mucosal injury in the rats. These effects appeared to be associated with antioxidant activity, activation of the production of PGE2, suppression of inflammatory cell infiltration and loss of epithelial cells in the gastric mucosa. Collectively, SAWE may be beneficial in the prevention of gastric disease associated to oxidative stress.

Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers.

This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-α and IL1-β expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-α and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-α.

NESFATIN-1 TREATMENT ALLEVIATES INDOMETHACIN-INDUCED GASTRIC ULCER IN RATS

Background: Indomethacin is a non-steroidal anti-inflammatory drug which is known to produce serious adverse effects including ulcerative lesions. Nesfatin-1, is an identified anorexigenic peptide to have antioxidant effects. Objective: This study aimed to investigate the possible ameliorative effect of nesfatin-1 against indomethacin induced gastric ulcer in rats, with exploration of the possible mechanisms underlying this effect. Materials and methods: Twenty four adult male albino rats were the animal model of this study. Ulcers were induced using oral indomethacin (20mg/kg) daily for 7 days. The rats were randomly assigned to vehicle-treated control group (I), indomethacin-treated (II), and indomethacin-treated for 7 days followed by nesfatin-1 (1ug/kg i.p) daily for 10 days. Assessment of gastric juice parameters (total acid output, pepsin activity and mucin content),gastric mucosal levels of malondialdehyde (MDA) , tumor necrosis factor –alpha (TNF-alpha) , nitrite and prostaglandin E2 (PGE2) levels were also determined. This in addition to assessment of gastric lesions and histopathologic examination of the gastric mucosa in each group. Results: Nesfatin-1 displayed a significant ameliorative effect in gastric lesions induced by indomethacin as indicated by a significant decrease in ulcer index and improved histopathology, along with a significant reduction in measured gastric juice parameters .It also reduced both gastric mucosal MDA and TNF-alpha significantly and increased nitrite and PGE2 levels in this ulcer model. Conclusion: Nesfatin-1 attenuates indomethacin- induced gastric ulcer and potentiates ulcer healing in the stomach of rats exposed to chronic administration of indomethacin. This effect depended upon decrease in gastric secretion, increase in nitric oxide and PGE2, besides an antioxidant anti-inflammatory role.

Ameliorative effect of the sea cucumber Holothuria arenicola extract against gastric ulcer in rats

Holothuria arenicola is the most important and abundant sea cucumber species in the Mediterranean Sea on the Egyptian coast. This work aimed to investigate the prophylactic and the curative effects of H. arenicola extract HaE (200mg/kg) on gastric mucosal damage following indomethacin and cold stress in healthy rats. Sixty-four rats were randomly divided into four main groups. Rats of the first group (8 rats/group) were administered distilled water orally (control group), rats of the second group (8 rats/group) were administered single oral dose of indomethacin (150mg/kg) and exposed to cold stress (4±1°C) for 30min to induce gastric ulcer (GU) model (ulcer group), rats of the third group, prophylactic group (24 rats/group) were treated with HaE and/or ranitidine (RAN) and then exposed to GU and rats of the fourth group, curative group (24 rats/group) were exposed firstly to GU and then treated with HaE and/or RAN. The results clearly indicate that pre-treatment with HaE and/or ranitidine significantly decreases the ulcer index, showing 72.50%, 53.11% and 80.56% ulceration inhibition, respectively. However, post-treatment with HaE and/or ranitidine significantly decreases the ulcer index, showing 51.66%, 62.41% and 67.78% ulceration inhibition, respectively. The results also showed that pre and post-treatment with HaE and/or RAN significantly decreased gastric malondialdehyde (MDA) level and enhanced reduced glutathione (GSH), catalase (CAT), glutathione-S-transferase (GST) and superoxide dismutase (SOD) levels. The results clearly indicate that pre-treatment with HaE is preferable.