Mucosal Malondialdehyde Research Articles

Effect of N-acetyl-L-cysteine administration in drinking water of broilers exposed to heat stress on performances, intestinal integrity, and oxidative status

Supplementing the diet of broiler with N-acetyl-L-cysteine (NAC) has been shown to support small intestinal integrity, and as a precursor of L-cysteine, it may also support antioxidant functions. As heat-stressed chickens suffer from intestinal disturbances caused by oxidative stress and at the same time increase water consumption, it was hypothesised that NAC supplemented via the drinking water could reinforce finisher broiler productivity under heat stress. Hence, three hundred 15-day-old male Ross 308 broilers were assigned to three treatments until 39 days of age: thermoneutral (TN), heat-stressed (HS), or HS + NAC. NAC was administered to the drinking water at 1000 mg/L starting on day 20. At 22 days, a chronic cyclic heat stress model was initiated in the HS and HS + NAC groups. On day 39, birds were euthanized and sampled for physiological measurements. Heat stress significantly decreased weight gain and feed intake from 22 to 39 days but did not affect feed efficiency. Rectal temperature and respiration rate significantly increased in heat-stressed broilers on days 23, 30, and 38. Also, ileal mucosal malondialdehyde (MDA) and plasma MDA levels were significantly higher in the HS group and the HS + NAC group, respectively, as compared to the TN group, whereas MDA levels in lung tissue were lower in both HS groups. Small intestinal villus height was significantly lower and serum FITC-d levels were significantly higher in the HS group compared to the TN group, without the effect of NAC supplementation. Furthermore, hepatic gene transcript of glutamate-cysteine ligase catalytic subunit was upregulated under heat stress conditions which may reflect higher glutathione synthesis, whereas in HS + NAC birds cystathionine-beta synthase-like (CBSL) mRNA level was dramatically reduced, indicating decreased transsulfuration activity. In conclusion, the administration of 1000 mg/L NAC in drinking water did not alleviate the reduced performances of heat-stressed finisher broilers. Nevertheless, it resulted in the downregulation of CBSL expression, suggesting a potential methionine-sparing effect.

Herbal cake-separated moxibustion relieves aspirin induced gastric mucosal injury by activating Nrf2/ARE/HO-1 signaling in rats

To investigate whether herbal cake-separated moxibustion can activate nuclear factor erythroid 2-related factor 2 （Nrf2） / antioxidant responsive element （ARE） /hemeoxygenase-1 （HO-1） signaling pathway to repair aspirin induced gastric mucosal injury （GMI） in rats. SD rats （half male and half female） were randomly divided into blank control, model, moxibustion, inhibitor of HO-1 （inhibitor）, model+inhibitor, moxibustion + inhibitor groups, with 20 rats in each group. The GMI model was established by gavage of aspirin 150 mg/kg（1 mL/100 g）. Herbal cake-separated moxibustion was alternatively applied to bilateral "Zusanli" （ST36） and "Zhongwan" （CV12） and bilateral "Pishu" （BL20） and "Weishu" （BL21） for 30 min, once daily for 8 days. The rats in the three inhibitor groups received intraperitoneal injection of HO-1 inhibitor zinc protoporphyrin （5 mg/kg）. The rats' behavior score, emotional response score, skin hair score, diet score and stool state score were given. The GMI index was calculated according to Guth's methods. Histopathological changes of gastric mucosa were observed by H.E. staining. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the gastric mucosal tissue and serum were detected by ELISA. The levels of Nrf2/ARE/HO-1 signaling pathway-related factors Keap1, Nrf2, HO-1, CAT, GST, and NQO1 in the gastric mucosal tissue were detected by quantitative real-time PCR and Western blot, separately. Compared with the blank control group, the behavior score, emotional response score, skin hair score, diet score and stool state score, GMI index, MDA contents of gastric mucosal tissue and serum, expression le-vels of Keap1 mRNA and protein were significantly increased （P<0.01）, while the activity of gastric mucosal and serum SOD, the expression levels of Nrf2, HO-1, CAT, GST and NQO1 mRNAs and proteins were considerably decreased （P<0.01） in the model group. Compared with the model group, moxibustion obviously reversed the increase of emotional response score, skin hair score, stool state score, GMI index, MDA levels of gastric mucosal tissue and serum, and expression levels of Keap1 mRNA and protein （P<0.01, P<0.05）, and the decrease of activity of SOD of gastric mucosal and serum, and the expression levels of Nrf2, HO-1, CAT, GST and NQO1 mRNAs and proteins （P<0.01, P<0.05）. After administration of antagonist of HO-1, the effects of moxibustion were eliminated or weakened pronouncedly in reducing skin hair score, GMI index, contents of gastric mucosal and serum MDA, and expression of Keap1 mRNA and protein, and in up-regulating gastric mucosal and serum SOD, and expression of HO-1, CAT, GST and NQO1 mRNAs and proteins （P<0.01, P<0.05）. Herbal-cake separated moxibustion can improve the GMI in rats, which may be associated with its effects in reducing oxidative stress and activating Nrf2/ARE/HO-1 signaling pathway.

Herbal cake-separated moxibustion relieves aspirin induced gastric mucosal injury by activating Nrf2/ARE/HO-1 signaling in rats

To investigate whether herbal cake-separated moxibustion can activate nuclear factor erythroid 2-related factor 2 （Nrf2） / antioxidant responsive element （ARE） /hemeoxygenase-1 （HO-1） signaling pathway to repair aspirin induced gastric mucosal injury （GMI） in rats. SD rats （half male and half female） were randomly divided into blank control, model, moxibustion, inhibitor of HO-1 （inhibitor）, model+inhibitor, moxibustion + inhibitor groups, with 20 rats in each group. The GMI model was established by gavage of aspirin 150 mg/kg（1 mL/100 g）. Herbal cake-separated moxibustion was alternatively applied to bilateral "Zusanli" （ST36） and "Zhongwan" （CV12） and bilateral "Pishu" （BL20） and "Weishu" （BL21） for 30 min, once daily for 8 days. The rats in the three inhibitor groups received intraperitoneal injection of HO-1 inhibitor zinc protoporphyrin （5 mg/kg）. The rats' behavior score, emotional response score, skin hair score, diet score and stool state score were given. The GMI index was calculated according to Guth's methods. Histopathological changes of gastric mucosa were observed by H.E. staining. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the gastric mucosal tissue and serum were detected by ELISA. The levels of Nrf2/ARE/HO-1 signaling pathway-related factors Keap1, Nrf2, HO-1, CAT, GST, and NQO1 in the gastric mucosal tissue were detected by quantitative real-time PCR and Western blot, separately. Compared with the blank control group, the behavior score, emotional response score, skin hair score, diet score and stool state score, GMI index, MDA contents of gastric mucosal tissue and serum, expression le-vels of Keap1 mRNA and protein were significantly increased （P<0.01）, while the activity of gastric mucosal and serum SOD, the expression levels of Nrf2, HO-1, CAT, GST and NQO1 mRNAs and proteins were considerably decreased （P<0.01） in the model group. Compared with the model group, moxibustion obviously reversed the increase of emotional response score, skin hair score, stool state score, GMI index, MDA levels of gastric mucosal tissue and serum, and expression levels of Keap1 mRNA and protein （P<0.01, P<0.05）, and the decrease of activity of SOD of gastric mucosal and serum, and the expression levels of Nrf2, HO-1, CAT, GST and NQO1 mRNAs and proteins （P<0.01, P<0.05）. After administration of antagonist of HO-1, the effects of moxibustion were eliminated or weakened pronouncedly in reducing skin hair score, GMI index, contents of gastric mucosal and serum MDA, and expression of Keap1 mRNA and protein, and in up-regulating gastric mucosal and serum SOD, and expression of HO-1, CAT, GST and NQO1 mRNAs and proteins （P<0.01, P<0.05）. Herbal-cake separated moxibustion can improve the GMI in rats, which may be associated with its effects in reducing oxidative stress and activating Nrf2/ARE/HO-1 signaling pathway.

Cornu aspersum mucin attenuates indomethacin-induced gastric ulcers in mice via alleviating oxidative stress and inflammation

In the past three decades, a significant progress has been made in the prevention and treatment of gastric ulcers. The incidence of the disease has decreased, but gastric ulcer is still a medical problem. Currently, the available drugs for gastric ulcer treatment have many side effects; therefore, searching for new and safe therapeutic agents is mandatory. The present study aims to investigate the gastroprotective potential of Cornu aspersum (C. aspersum) mucin against gastric ulcers, and the mechanisms related to oxidative stress and inflammation. C. aspersum mucin was collected from 50 snails. The characteristics of C. aspersum mucin (chemical and microbiological) were evaluated. Mice were pretreated with famotidine and C. aspersum mucin (7.5 and 15 ml/kg b.w.) for 5 days, and then gastric ulcers were induced by indomethacin. Macroscopic examination, biochemical estimations, and Quantitative real-time PCR were carried out. Also, histopathological and immunohistopathological examinations were evaluated. We found that the high dose of the mucin significantly decreased the gastric mucosal malondialdehyde (MDA) and nitric oxide (NO) contents as well as interleukin 1β (IL-1β) and nuclear factor kappa β (NF-ҡB) expression, and inducible nitric oxide synthase (iNOS) immunostaining. It also increased the gastric mucosal GSH and catalase contents as well as hemoxygenase-1 (HO-1) and nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions with regressions in gastric mucosal lesions. In conclusion, C. aspersum mucin could be a potential therapeutic candidate to protect against gastric ulceration.

Remifentanil Promotes PDIA3 Expression by Activating p38MAPK to Inhibit Intestinal Ischemia/Reperfusion-Induced Oxidative and Endoplasmic Reticulum Stress.

Background: Remifentanil protects against intestinal ischemia/reperfusion (I/R) injury; however, its exact mechanism remains to be elucidated. The objective of this study was to investigate the underlying molecular mechanism of remifentanil in intestinal I/R injury in mice. Methods: We evaluated the intestine-protective effect of remifentanil in adult male mice with 45 min superior mesenteric artery occlusion followed by 4 h reperfusion by determining the following: intestinal Chiu’s scores, diamine oxidase, and intestinal fatty acid binding protein in serum; the apoptotic index, lipid peroxidation product malondialdehyde (MDA), and superoxide dismutase (SOD) activity in the intestinal mucosa; and the intestinal mRNA and protein expressions of Bip, CHOP, caspase-12, and cleaved caspase-3, reflecting endoplasmic reticulum (ER) stress. Furthermore, conditional knockout mice, in which the protein disulfide isomerase A3 (PDIA3) gene was deleted from the intestinal epithelium, and SB203580 (a selective p38MAPK inhibitor) were used to determine the role of PDIA3 and p38MAPK in I/R progression and intestinal protection by remifentanil. Results: Our data showed that intestinal I/R induced obvious oxidative stress and endoplasmic reticulum stress–related cell apoptosis, as evidenced by an increase in the intestinal mucosal malondialdehyde, a decrease in the intestinal mucosal SOD, and an increase in the apoptotic index and the mRNA and protein expression of Bip, CHOP, caspase-12, and cleaved caspase-3. Remifentanil significantly improved these changes. Moreover, the deletion of intestinal epithelium PDIA3 blocked the protective effects of remifentanil. SB203580 also abolished the intestinal protection of remifentanil and downregulated the mRNA and protein expression of PDIA3. Conclusion: Remifentanil appears to act via p38MAPK to protect the small intestine from intestinal I/R injury by its PDIA3-mediated antioxidant and anti-ER stress properties.

Dietary Lycopene Supplementation Could Alleviate Aflatoxin B1 Induced Intestinal Damage through Improving Immune Function and Anti-Oxidant Capacity in Broilers.

Simple SummaryAflatoxin B1 (AFB1) is a common and devastating food-borne fungal toxic in the broiler industry. AFB1 has adverse effects on the world poultry industry as it impairs the health, performance, intestinal integrity, and immunity of broilers. There has been a great economic concern in the global poultry production, leading to billions of dollars loss every year due to AFB1. Antibiotic-free broiler production relies on feed supplementation as an alternative to antibiotic usage. We previously reported that dietary supplementation with lycopene (LYC) has shown a promising effect on performance and intestinal integrity in the broilers infected with AFB1. However, there are few reports on the effects of LYC on the intestinal development and antioxidant capacity in the broiler against AFB1. The present study was conducted to evaluate the effects of LYC supplementation on the intestinal immune function, barrier function, and antioxidant capacity of broilers fed with an AFB1 contaminated diet. The findings of this research highlighted that the diet supplemented with LYC has a potential effect to improve intestinal health and reduce AFB1 related oxidative and inflammatory status. Hence, this study suggested that addition of LYC in broiler poultry production alleviates the AFB1 toxicity.The present study aims to evaluate the effects of lycopene (LYC) supplementation on the intestinal immune function, barrier function, and antioxidant capacity of broilers fed with aflatoxinB1 (AFB1) contaminated diet. A total of 144 one-day-old male Arbor Acres broilers were randomly divided into three dietary treatment groups; each group consisted of six replicates (eight birds in each cage). Treatments were: (1) a basal diet containing neither AFB1 nor LYC (Control), (2) basal diet containing 100 µg/kg AFB1, and (3) basal diets with 100 µg/kg AFB1 and 200 mg/kg LYC (AFB1 and LYC). The results showed that dietary LYC supplementation ameliorated the AFB1 induced broiler intestinal changes by decreasing the inflammatory cytokines interferon-γ (IFN-γ), interleukin 1beta (IL-1β), and increasing mRNA abundances of cludin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in the jejunum mucosa. On the other hand, AFB1-induced increases in serum diamine oxidase (DAO) activities, D-lactate concentration, mucosal malondialdehyde (MDA), and hydrogen peroxide (H2O2) concentrations were reversed by dietary LYC supplementation (p < 0.05). Additionally, LYC supplementation ameliorated the redox balance through increasing the antioxidant enzyme activities and their related mRNA expression abundances compared to AFB1 exposed broilers. In conclusion, dietary supplementation with LYC could alleviate AFB1 induced broiler intestinal immune function and barrier function damage and improve antioxidants status.

Dietary chitosan oligosaccharides alleviate heat stress–induced intestinal oxidative stress and inflammatory response in yellow-feather broilers

The purpose of this study was to evaluate the effects of chitosan oligosaccharides (COS) on intestinal permeability, morphology, antioxidant status, and inflammatory response in heat-stressed broilers. A total of 108 thirty-five-day-old Chinese yellow-feather broilers (body weight 470.31 ± 13.15 g) were randomly allocated to 3 dietary treatments as follows: CON group, basal diet and raised under normal temperature (24°C); HS group, basal diet and raised under cycle heat stress (34°C from 10:00–18:00 and 24°C for the rest time); HSC group, basal diet with 200 mg/kg COS supplementation and raised under cycle heat stress. Each treatment had 6 replication pens and 6 broilers per pen. Compared with the CON group, heat stress decreased (P < 0.05) the relative weight of duodenum and jejunum; the relative length and villus height (VH) of duodenum, jejunum, and ileum; the ileum VH to crypt depth ratio; duodenum mucosal catalase (CAT) activity; and jejunum mucosal glutathione peroxidase (GSH-Px) and CAT activity, whereas it increased (P < 0.05) serum diamine oxidase (DAO) activity and D-lactate acid (D-LA) content, duodenum and jejunum mucosal malondialdehyde (MDA) and interleukin-1β (IL-1β) content, and ileum mucosal tumor necrosis factor-α content. Compared to the HS group, dietary COS supplementation increased (P < 0.05) the relative length of duodenum, jejunum, and ileum; the VH of jejunum and ileum; and duodenum and jejunum mucosal GSH-Px activity, whereas it decreased (P < 0.05) serum DAO activity and D-LA concentration and duodenum and jejunum mucosal MDA and IL-1β content. These results suggested that dietary COS supplementation had beneficial effects on intestinal morphology by increasing jejunum and ileum VH; permeability by decreasing serum DAO activity and D-LA content; antioxidant capacity by decreasing duodenum and jejunum mucosal MDA content and by increasing duodenum and jejunum GSH-Px activity; and inflammatory response by decreasing duodenum and jejunum mucosal IL-1β content.

Laxative and antioxidant effects of ramie (Boehmeria nivea L.) leaf extract in experimental constipated rats.

Ramie leaf (Boehmeria nivea L.) is rich in cellulose, polyphenol compounds, vitamin C, and minerals. The leaves of this plant, which are used for medicinal purposes, have long been reported to have anti‐inflammatory, antioxidant, anticolitis, and antidiabetic effects. We investigated the protective effects of ramie leaf ethanol extract (RLE) against loperamide‐induced constipation and oxidative stress in rats. Male Sprague‐Dawley rats were administered 200 or 400 mg/kg body weight of RLE (RLEL and RLEH groups) by gavage, while normal (NOR) and control (CON) rats received saline. Loperamide (4.0 mg/kg, twice per day) was injected subcutaneously to induce constipation in RLEL, RLEH, and CON groups. Total fecal number, wet weight, and water content decreased, while the total number of loperamide‐induced fecal pellets in the distal colon increased with administration of RLE in a dose‐dependent manner. Gastrointestinal transit time was more greatly reduced in RLE‐treated groups than in the CON group. Serum total cholesterol (TC) level, as well as alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activity, was significantly lower in both RLEL and RLEH groups compared with the CON group. Intestinal mucosa malondialdehyde (MDA) and hydrogen peroxide (H2O2) production decreased significantly in a dose‐dependent manner in the RLE‐treated groups. Loperamide decreased the antioxidant enzyme activity, including that of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), while RLE administration increased the antioxidant activity. These results suggest that RLE exerts potent laxative and antioxidant effects in model rats with loperamide‐induced constipation.

Age-dependent Role of Cilostazol on Cold Restraint Stress-induced Gastric Ulceration in Female Rats

Introduction: Cilostazol (CIL), a phosphodiesterase III inhibitor, is a potent antiplatelet drug which possesses vasodilator and anti-inflammatory activity that making it an effective drug in gastric ulcer protection. Objectives: This study investigated the influence of age on the effects of CIL against cold restraint stress (CRS) - induced gastric ulcer in rats. Methods: CIL (10 mg/kg/day) was administered orally for 2 weeks to adult and aged female rats before CRS-induced gastric ulcer. Results: This syudy showed that CIL exhibited gastroprotective effects in both adult and aged rats as evidenced by significant decrease in ulcer index, gastric mucosal malondialdehyde level, myeloperoxidase activity and tumor necrosis factor-α protein expression with concomitant increase in gastric mucosal reduced glutathione level and glutathione peroxidase activity, nitric oxide, prostaglandin E2 level, cyclooxygenase-1 and 2 protein expression and gastric juice mucin concentration compared to adult and aged CRS rats, respectively. Additionally, the histopathological examination results came to confirm the protection afforded by CIL in CRS - induced gastric ulcer. Conclusion: The possible protective effect of CIL against CRS-induced gastric ulceration in both adult and aged rat’s may be explained via its antioxidant and antiinflammatory properties and by enhancement of gastric mucus secretion. It could be recommended that CIL is considered as a more proper antiplatelet drug for adult and elderly patients who are at risk of gastric ulceration.

124 Impact of heat stress and antioxidant supplements in feed or drinking water on growth, intestinal morphology, and oxidative and immune status in growing pigs

Abstract The objective of this study was to evaluate the impact of vitamin E (vitE) or polyphenols supplemented in feed or drinking water as a heat abatement strategy in growing pigs. Individually housed pigs (n = 128, 47.3 ± 5.0 kg BW) were assigned within weight blocks and sex to a 2x4 factorial arrangement consisting of 2 environments (thermo-neutral [21.2°C] or heat-stressed [30.9°C]) and 4 supplementation treatments (control diet [25 IU/kg dl-α-tocopherol acetate]; control+100 IU/L vitE [d-α-tocopherol] in water; control+200 IU/kg vitE [dl-α-tocopherol acetate] in feed; or control+400 mg/kg polyphenols in feed). Supplementation was started 7 d prior to temperature treatments applied for 28 d. Heat stress reduced (P ≤ 0.001) final BW, ADG, and ADFI (-7.4 kg, -26.7%, and -25.4%, respectively) and increased (P &amp;lt; 0.001) respiration rate and rectal temperature, but no effects of supplementation were detected. Serum vitamin E concentration increased (P &amp;lt; 0.001) with vitE supplementation (1.64, 3.59, 3.24, and 1.67 mg/kg for control, vitE in water, vitE in feed, and polyphenols, respectively) and was greater when supplemented in water vs. feed (P = 0.002), especially when measured on d 28 (chronic) vs. d 2 (acute) of heat stress. Liver vitamin E increased (P &amp;lt; 0.001) with vitE supplementation, especially in water, but not polyphenols (3.9, 31.8, 18.0, 4.9 ppm for control, vitE in water, vitE in feed, and polyphenols, respectively). Serum malondialdehyde (MDA) was greater (P &amp;lt; 0.05) for supplemented pigs compared to control, and heat stress reduced (P = 0.014) serum MDA on d 2, but not d 28. No differences were detected for intestinal morphology or MDA in mucosa of jejunum or ileum. Heat stress decreased (P &amp;lt; 0.03) TNF-α in mucosa of ileum and jejunum, and supplementation reduced (P &amp;lt; 0.05) TNF-α in mucosa of the ileum, but not jejunum. Heat stress markedly reduced performance of growing pigs, and supplementing antioxidants in feed or water was not effective in alleviating the impact of heat stress.

Dietary supplementation of xylanase and protease on growth performance, digesta viscosity, nutrient digestibility, immune and oxidative stress status, and gut health of newly weaned pigs

This study was to investigate the effect of dietary supplementation with xylanase and protease on growth performance, digesta viscosity, apparent ileal digestibility (AID) of nutrients, and gut health in nursery pigs. Forty-eight pigs (24 barrows and 24 gilts at 21 d of age with 7.2 ± 0.4 kg BW) were randomly allotted to 4 dietary treatments (2 × 2 factorial arrangement) in a randomized complete block design and fed in 2 phases (phase 1 for 10 d and phase 2 for 14 d). Factors were xylanase (0 or 45,000 XU/kg) and protease (0 or 300,000 U/kg). Feed intake and BW gain were measured on d 10 and 24. Titanium dioxide (0.25%) was added to all diets as an indigestible external marker from d 20 to 24. On d 24, all pigs were euthanized to obtain jejunal and ileal digesta to measure viscosity and apparent ileal digestibility. The jejunal mucosa was collected to measure immune and oxidative stress status. Jejunal tissues were used to measure morphology and crypt cells proliferation. In phase 2, xylanase increased (P < 0.05) the average daily gain (ADG) which was further increased (P < 0.05) when combined with protease. Overall, combinational use of xylanase and protease increased (P < 0.05) ADG compared with the use of xylanase or protease alone, whereas protease improved (P < 0.05) feed efficiency. In jejunum, xylanase reduced (P < 0.05) viscosity of digesta, mucosal malondialdehyde (MDA), crypt depth and crypt cells proliferation, and protease increased (P < 0.05) villus height, and decreased (P < 0.05) crypt depth and crypt cells proliferation. Collectively, xylanase improved growth performance, digesta viscosity, and oxidative stress, whereas protease improved feed efficiency and gut morphology. The combinational use of xylanase and protease enhanced growth performance of newly weaned pigs.

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.

Adeno-associated virus-mediated colonic secretory expression of HMGB1 A box attenuates experimental colitis in mice.

Extracellular high mobility group box 1 (HMGB1) is crucially implicated in the pathogenesis of inflammatory bowel diseases (IBDs). A box domain of HMGB1 has been identified as a specific antagonist of HMGB1. In the present study, we tested the effects of adeno-associated virus (AAV)-mediated colonic secretory expression of HMGB1 A box on murine experimental colitis. Self-complementary AAV-2 carrying mouse immunoglobin Gκ leader-human HMGB1 A box (AAV-HMGB1 A box) was constructed. The effects of intracolonically administered AAV-HMGB1 A box on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were assessed by the disease activity index (DAI), colon length, macroscopic and histological scoring, myeloperoxidase (MPO) activity, and epithelial apoptosis and complementary proliferation. Colonic immune cell infiltrates, mucosal malondialdehyde content and superoxide dismutase activity, colonic tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 levels, serum HMGB1 concentration, and colonic HMGB1 release were determined to investigate the underlying mechanisms. Intracolonically administered AAV-HMGB1 A box efficiently mediated secretory expression of HMGB1 A box and led to significant decreases in DAI, macroscopic and histological scores and colonic epithelial apoptosis in both DSS- and TNBS-treated mice. Modulating inflammation-associated cytokines, such as inhibiting colonic TNF-α and IL-1β expression, decreasing HMGB1 release, and restoring colonic IL-10 levels, and thereby inhibiting inflammatory cell infiltration and alleviating oxidant damage, might be the underlying mechanism. Intracolonic application of AAV-HMGB1 A box is effective in alleviating murine colitis and has therapeutic potential in human IBDs.

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.

Malondialdehyde and SOD-induced changes of gastric tissues in acute gastric mucosal injury under positive acceleration.

The aim of this study was to investigate the impacts of positive acceleration (+Gz) on the gastric mucosal tissues in cases of acute gastric mucosal injury and to explore the role of oxygen free radicals. Thirty Sprague Dawley rats were randomly divided into the absolute ethanol control group (A group), absolute ethanol +5Gz group (B group), absolute ethanol +10Gz group (C group). Following centrifugation, the gastric tissues of each group were studied for the presence of gastric mucosal injuries and morphological changes. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) contents were simultaneously investigated. Degree of gastric mucosal injuries were as follows: C group (visually 49.080 ± 10.254, under light microscopy 9.400 ± 2.011) > B group (visually 23.654 ± 9.678, under light microscopy 5.000 ± 1.054) > A group (visually 11.410 ± 3.742, under light microscopy 3.800 ± 1.399). The gastric mucosal MDA content (0.376 ± 0.084 vs 0.235 ± 0.044) was significantly higher in the C group than in the A group, whereas the SOD content (8.852 ± 1.001 vs 10.694 ± 0.965) was lower than that in the A group. However, the MDA and SOD contents did not change much in the B group. Our results suggest that the +Gz exposure might aggravate the acute gastric mucosal injury, and changes in MDA and SOD contents in the gastric tissues indicated that the oxygen free radicals play an important role in this regard.

Gastroprotective potentials of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats

This study investigated the protective effects of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats. Gastric ulceration was induced by single intraperitoneal injection of indomethacin (30 mg/kg b.wt.). M. maderaspatana extract produced significant reduction in gastric mucosal lesions, malondialdehyde and serum tumour necrosis factor-α associated with a significant increase in gastric juice mucin content and gastric mucosal catalase, nitric oxide and prostaglandin E2 levels. The volume and acidity of the gastric juice decreased in pretreated rats. The plant extract was evaluated in the gastric juice of rats, untreated has showed near normal levels in pretreated rats. The M. maderaspatana was able to decrease acidity and increase the mucosal defence in the gastric area, therefore justifying its use as an antiulcerogenic agent. Ranitidine significantly increased pH value and decreased pepsin activity and gastric juice free and total acidity. The anti-ulcer effect was further confirmed histologically.

The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa.

Background/AimsThe aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage.MethodsThe enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (−) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a 13C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay.ResultsBSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups.ConclusionsBSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.

Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production

Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production.

The effect of a minor constituent of essential oil from Citrus aurantium: The role of β-myrcene in preventing peptic ulcer disease

The monoterpene β-myrcene has been widely used in cosmetics, food and beverages, and it is normally found in essential oil from citrus fruit. The aim of this study was to investigate the anti-ulcer effects of β-myrcene on experimental models of ulcers that are induced by ethanol, NSAIDs (non-steroidal anti-inflammatory drugs), stress, Helicobacter pylori, ischaemia–reperfusion injury (I/R) and cysteamine in order to compare with the essential oil of Citrus aurantium and its major compound limonene. The results indicate that the oral administration of β-myrcene at a dose of 7.50mg/kg has important anti-ulcer activity with significantly decreased gastric and duodenal lesions as well as increased gastric mucus production. The results showed treatment with β-myrcene caused a significant increase in mucosal malondialdehyde level (MDA), an important index of oxidative tissue damage. The β-myrcene was also endowed with marked enhancement of antioxidant enzyme activity from GR system as evidenced by the decreased activity of superoxide dismutase (SOD) and increased levels of glutathione peroxidase (GPx), glutathione reductase (GR), and total glutathione in gastric tissue. Our results also shown that treatment with β-myrcene is not involved with thioredoxin reductase (TrxR) activity. Our results reveal, for the first time, the importance of β-myrcene as an inhibitor of gastric and duodenal ulcers and demonstrate that an increase in the levels of gastric mucosa defence factors is involved in the anti-ulcer activity of β-myrcene.

Mechanisms of the Protective Effects of Curcumin against Indomethacin-Induced Gastric Ulcer in Rats

Background/Aims: Curcumin, a naturally occurring polyphenolic compound, exhibits anti-inflammatory and antioxidant properties that render it an attractive candidate for protection against gastric ulcer. The aim of this study is therefore to evaluate the protective effects of curcumin against indomethacin-induced gastric ulcer in rats. Methods: Gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Curcumin (50 mg/kg, p.o.) was administered 30 min before ulcer induction. Results: Curcumin showed gastroprotective effects as evidenced by significant decreases in ulcer index, total acid output and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, and concomitant increases in gastric juice mucin concentration, gastric mucosal nitric oxide level and catalase and superoxide dismutase activities as compared to the indomethacin-induced ulcer group. Moreover, immunohistochemical investigations demonstrated that curcumin treatment markedly decreased expression of inducible nitric oxide synthase, nuclear factor-κB, and caspase-3. Conclusion: Curcumin protected the rats' gastric mucosa against indomethacin-induced gastric ulceration possibly, at least in part, by enhancement of the gastric mucosal barrier and reduction in acid secretory parameters in addition to antioxidant and antiapoptotic activities.