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MPO Activity (mpo + activity)
Selected AbstractsEvaluation of systemic oxidative status and mononuclear leukocytes DNA damage in children with caustic esophageal strictureDISEASES OF THE ESOPHAGUS, Issue 4 2006M. Kaya SUMMARY., Esophageal stricture (ES) due to accidentally caustic digestions is a common problem in children. Mucosal damage and repeated dilatations lead to chronic inflammation and finally ES. We investigated the oxidative status and DNA damage of children with ES. Five children with ES were compared with the same age- and sex-matched healthy subjects. Oxidative status of plasma was evaluated by measuring myeloperoxidase (MPO) activity, and total peroxide (TP) level. Anti-oxidative status of the plasma was evaluated by measuring catalase (CAT) activity, and total antioxidant response (TAR). We used the Single Cell Gel Electrophoresis (also called Comet Assay) to measure DNA strand break in peripheral blood mononuclear leukocytes. Mean MPO activity and TP levels in the ES group were significantly higher than the control group (0.83 ± 0.35, 0.09 ± 0.03 and 0.98 ± 0.38, 0.34 ± 0.20, P = 0.009 and P = 0.047 respectively). There was no significant difference in CAT activity and TAR levels between the two groups (P = 0.347). DNA damage in patients with ES was increased compared to control subjects (108.8 ± 51.2 and 57.6 ± 31.2 arbitrary units, respectively), but this difference was not significant statistically (P= 0.09). This study shows that systemic oxidative stress and alteration at the nuclear level occur in patients with ES, as a result of multiple dilatations and tissue injury. On the other hand, these results support that patients with ES may benefit from antioxidant treatment. [source] Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regeliiEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2009D. H. Kim Abstract Background, Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation. Materials and methods, Anti-inflammatory effects of celastrol (0,1 ,M) were examined in lipopolysaccharide (LPS)-stimulated RAW 264·7 macrophages. To investigate the effects of celastrol (0,50 ,g per mice) in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12- O -tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear oedema model. Results, Our in vitro experiments showed that celastrol suppressed not only LPS-stimulated generation of nitric oxide and prostaglandin E2, but also expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264·7 cells. Similarly, celastrol inhibited LPS-induced production of inflammatory cytokines, including tumour necrosis factor-, and interleukin-6. In an animal model, celastrol protected mice from TPA-induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines. Conclusions, Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases. [source] Dipeptidyl peptidase expression during experimental colitis in miceINFLAMMATORY BOWEL DISEASES, Issue 8 2010Roger Yazbeck PhD Abstract Background: We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection. Materials and Methods: Wildtype (WT) and DPIV,/, mice consumed 2% DSS in drinking water for 6 days to induce colitis. Mice were treated with saline or the DP inhibitors Ile-Pyrr-(2-CN)*TFA or Ile-Thia. DP mRNA and enzyme levels were measured in the colon. Glucagon-like peptide (GLP)-2 and GLP-1 concentrations were determined by radioimmunoassay, regulatory T-cells (Tregs) by fluorescence activated cell sorting (FACS) on FOXp3+T cells in blood, and neutrophil infiltration assessed by myeloperoxidase (MPO) assay. Results: DP8 and DP2 mRNA levels were increased (P < 0.05) in WT+saline mice compared to untreated WT mice with colitis. Cytoplasmic DP enzyme activity was increased (P < 0.05) in DPIV,/, mice at day 6 of DSS, while DP2 activity was increased (P < 0.05) in WT mice with colitis. GLP-1 (63%) and GLP-2 (50%) concentrations increased in WT+Ile-Pyrr-(2-CN)*TFA mice compared to day-0 controls. MPO activity was lower in WT+Ile-Thia and WT+Ile-Pyrr-(2-CN)*TFA treated mice compared to WT+saline (P < 0.001) at day 6 colitis. Conclusions: DP expression and activity are differentially regulated during DSS colitis, suggesting a pathophysiological role for these enzymes in human inflammatory bowel disease (IBD). DP inhibitors impaired neutrophil recruitment and maintenance of the Treg population during DSS-colitis, providing further preclinical evidence for the potential therapeutic use of these inhibitors in IBD. Finally, DPIV appears to play a critical role in mediating the protective effect of DP inhibitors. Inflamm Bowel Dis 2010 [source] Kinetics of inhibition of peroxidase activity of myeloperoxidase by quercetinINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 7 2008Tatjana Momi The inhibition of myeloperoxidase (MPO), isolated from human neutrophils, by quercetin was investigated by following peroxidase activity of the enzyme using o -dianisidine as the substrate. The inhibition parameters (IC50) were obtained by graphical analysis of the inhibition curves. A reaction mechanism, which involved the enzyme inhibition by quercetin and H2O2 in excess, was proposed. The rate and equilibrium constants for the proposed reaction path were calculated from experimental data. Kinetic analysis in noninhibiting H2O2 concentration range in the absence and the presence of quercetin revealed that the reaction mechanism underwent Michaelis,Menten kinetics. K and V values indicated that quercetin was a mixed inhibitor of MPO activity. The initial reaction rates were recalculated using the obtained results. Calculated curves fitted the experimental results within the range of experimental error. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 384,394, 2008 [source] The effect of sildenafil, a phosphodiesterase-5 inhibitor, on acetic acid-induced colonic inflammation in the ratJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2009Sevgin Ozlem Iseri Abstract Background and Aim:, Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid-induced colitis. Methods:, Colitis was induced by intrarectal administration of 1 mL of 5% acetic acid to Sprague-Dawley rats (200,250 g; n = 7,8/group). Control rats received an equal volume of saline intrarectally. In treatment groups, the rats were treated with either sildenafil citrate (5 mg/kg/day; subcutaneously) or saline for 3 days. After decapitation, distal colon was weighed and scored macroscopically and microscopically. Tissue samples were used for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and oxidant production. Trunk blood was collected for the assessment of serum tumor necrosis factor (TNF)-, and interleukin (IL)-1, levels. Results:, In the colitis group, the colonic tissue was characterized by lesions, increased lipid peroxidation with a concomitant reduction in GSH content, increased MPO activity and oxidant production. Serum TNF-, and IL-1, levels were higher in the colitis group compared to control values. Sildenafil reversed these inflammatory parameters nearly back to control values. Conclusions:, Sildenafil citrate administration to rats with acetic acid-induced colitis seems to be beneficial via prevention of lipid peroxidation, oxidant generation, cytokine production and neutrophil accumulation. [source] Role of interleukin-18 in the development of acute pulmonary injury induced by intestinal ischemia/reperfusion and its possible mechanismJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2007Yong-jie Yang Abstract Background and Aims:, Lung injury is an important target for the systemic inflammatory response associated with intestinal ischemia/reperfusion (I/R). In the present study, the role of interleukin (IL)-18 in the development of acute pulmonary injury induced by intestinal I/R and its possible mechanism in relation to the increased activity of inducible nitric oxide synthase and tumor necrosis factor (TNF)-, were investigated. Methods:, Mice were randomly divided into three groups: normal control group without operation; sham group with sham operation; and I/R group in which mice underwent superior mesenteric artery occlusion for 30 min followed by reperfusion for 3 h. Each group received pretreatment with exogenous IL-18, anti-IL-18 neutralizing antibody or L-NIL, the selective inhibitor of inducible nitric oxide synthase, 30 min before ischemia. The expression of TNF-, was detected by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Lung injury was evaluated by means of Evans blue dye (EBD) concentration, myeloperoxidase (MPO) activity and morphological analysis. Results:, The experimental results showed that both in the sham-operated and I/R groups of animals, pretreatment with exogenous IL-18 clearly enhanced pulmonary MPO activity, microvascular leakage and the expression of TNF-, mRNA and protein. In contrast, IL-18 did not increase the TNF-, level and degree of lung injury, although it clearly enhanced the pulmonary MPO activity in normal animals. Meanwhile, IL-18 antibody given prior to ischemia led to a reduction in the sequestration of neutrophils, extravasation of EBD and downregulation of the serum level of TNF-, in the I/R group of animals. In addition, selective inhibition of inducible nitric oxide synthase (iNOS) that inhibited plasma extravasation and pulmonary injury without affecting the MPO activity could be demonstrated in all treated animals. Conclusions:, These data suggested a role of IL-18 in the activation and sequestration of neutrophils in lungs. Our results were consistent with the hypothesis that increased sequestration of neutrophils and microvascular leakage might, respectively, relate to the increased IL-18 level and the elevation of TNF-,/iNOS activity, and these two aspects might synergically contribute to intestinal I/R-induced pulmonary dysfunction. [source] Protective effect of rebamipide on indomethacin-induced intestinal damage in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2001Hiroyuki Mizoguchi Abstract Background and Aim: We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. Methods: The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30,300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. Results: Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 ,g/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. Conclusion: These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action. [source] Antimicrobial activity of platelet-leukocyte gel against Staphylococcus aureusJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008Dirk Jan F. Moojen Abstract Platelet-leukocyte gel (PLG) contains high concentrations of platelets and leukocytes. As leukocytes play an important role in the innate host-defense, we hypothesized that PLG might have antimicrobial properties. This study investigated the antimicrobial activity of PLG against Staphylococcus aureus and the contribution of myeloperoxidase (MPO), present in leukocytes, in this process. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from whole blood of six donors. PLG was prepared by mixing PRP with autologous (PLG-AT) or bovine thrombin (PLG-BT). Antimicrobial activity of PLG-AT, PLG-BT, PRP, and PPP was determined in a bacterial kill assay. MPO release was measured by ELISA and activity was measured using a MPO activity assay. Cultures showed a rapid decrease in the number of bacteria for both PLG-AT and PLG-BT, which was maximal between 4 and 8 h, to approximately 1% of the bacteria in controls. The effect of PLG-AT was largest and significantly different compared to PRP (p,=,0.004) and PPP (p,<,0.001), however not compared to PLG-BT (p,=,0.093). PLG-AT, PLG-BT, and PRP showed a comparable, gradually increasing MPO release. MPO activity was comparable for all groups and remained stable. No correlation between MPO release, activity, and bacterial kill could be found. PLG appears to have potent antimicrobial capacity, but the role of MPO in this activity is questionable. PLG might represent a useful strategy against postoperative infections. However, additional research should elucidate its exact antimicrobial activity. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:404,410, 2008 [source] Pomegranate peel extract prevents liver fibrosis in biliary-obstructed ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2007Hale Z. Toklu ABSTRACT Punica granatum L. (pomegranate) is a widely used plant that has high nutritional value. The aim of this study was to assess the effect of chronic administration of pomegranate peel extract (PPE) on liver fibrosis induced by bile duct ligation (BDL) in rats. PPE (50 mg kg,1) or saline was administered orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin 1 beta) in the serum and anti-oxidant capacity (AOC) were measured in plasma samples. Samples of liver tissue were taken for measurement of hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemilumi-nescence assay. Serum AST, ALT, LDH and cytokines were elevated in the BDL group compared with the control group; this increase was significantly decreased by PPE treatment. Plasma AOC and hepatic GSH levels were significantly depressed by BDL but were increased back to control levels in the PPE-treated BDL group. Increases in tissue MDA levels and MPO activity due to BDL were reduced back to control levels by PPE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with PPE treatment. Thus, chronic PPE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function. It therefore seems likely that PPE, with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver from fibrosis and oxidative injury due to biliary obstruction. [source] Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptomsJOURNAL OF PINEAL RESEARCH, Issue 3 2009Mehmet Ersahin Abstract:, Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood,brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+ -K+ -ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+ -K+ -ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema. [source] Melatonin protects against endosulfan-induced oxidative tissue damage in ratsJOURNAL OF PINEAL RESEARCH, Issue 4 2008Gülden Z. Omurtag Abstract:, Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)-induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor-, (TNF-,), interleukin-, (IL-,) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF-, and IL-,), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan-treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan-induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant,antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity. [source] Melatonin limits lung injury in bleomycin treated miceJOURNAL OF PINEAL RESEARCH, Issue 2 2005Tiziana Genovese Abstract:, Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. The aim of this study was to investigate the effect of melatonin on the lung injury caused by bleomycin (BLM) administration. Mice subjected to intratracheal administration of BLM developed significant lung injury characterized by a marked neutrophil infiltration [assessed by myeloperoxidase (MPO) activity] and by tissue edema. In addition, an increase of immunoreactivity to nitrotyrosine, poly-ADP-ribose (PAR) was also observed in the lung of BLM-treated mice. Also, lung injury induced by BLM administration was correlated with a significant loss of body weight and with a significant mortality. Administration of melatonin (10 mg/kg i.p.) daily significantly reduced the (i) loss of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation and (v) histological evidence of lung injury. Administration of melatonin also markedly reduced the nitrotyrosine and PAR formation. Taken together, our results demonstrate that treatment with melatonin significantly reduces lung injury induced by BLM in the mice. [source] Melatonin treatment protects against ischemia/reperfusion-induced functional and biochemical changes in rat urinary bladderJOURNAL OF PINEAL RESEARCH, Issue 3 2003Göksel, ener Abstract: Reactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several systems. The aim of this study was to investigate the role of melatonin against I/R injury of the rat urinary bladder. The abdominal aorta was clamped to induce ischemia for 30 min, then the animals were subjected to 60 min of reperfusion. Melatonin (10 mg/kg, i.p.) or the vehicle (control 1% alcohol i.p.) was administered before I/R. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for measurement of products of lipid peroxidation (LP), glutathione (GSH) levels and myeloperoxidase activity (MPO). Bladder strips were suspended in oxygenated Tyrode's buffer at 37°C and isometric contractions to carbachol (CCh; 10,8,10,4 m) were recorded. In the I/R group, the contractile responses of the bladder strips were lower than those of the control group (P < 0.01,0.001) and were reversed by treatment with melatonin (P < 0.05,0.001). LP which was higher in I/R group compared with control (27.68 ± 1.69 and 10.59 ± 1.27 nmol/g, respectively; P < 0.001) was partially reversed by melatonin (19.01 ± 1.85 nmol/g; P < 0.01). Similarly, GSH showed a decrease in the I/R group compared with controls (0.27 ± 0.03 and 0.43 ± 0.04 ,mol/g, respectively; P < 0.05) and melatonin prevented this effect completely (0.45 ± 0.04 , mol/g; P < 0.05). MPO activity in the I/R group (4.19 ± 0.08 U/g) was significantly higher than that of the control group (1.41 ± 0.08 U/g; P < 0.001) and melatonin treatment reduced MPO levels compared with I/R alone (3.16 ± 0.07; P < 0.001). Melatonin almost completely reversed the low contractile responses of rat urinary bladder strips to CCh and prevented oxidative tissue damage following I/R. [source] Sirtinol attenuates hepatic injury and pro-inflammatory cytokine production following trauma-hemorrhage in male Sprague,Dawley ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2008F.-C. LIU Background: Although studies have demonstrated that sirtinol administration following adverse circulatory conditions is known to be protective, the mechanism by which sirtinol produces the salutary effects remains unknown. We hypothesized that sirtinol administration in male rats following trauma-hemorrhage decreases cytokine production and protects against hepatic injury. Methods: Male Sprague,Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). A single dose of sirtinol (1 mg/kg of body weight) or vehicle was administered intravenously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 levels in the liver and plasma alanine aminotransferase (ALT) concentrations were measured (n=6 Sprague,Dawley rats/group). Results: Trauma-hemorrhage increased hepatic MPO activity, CINC-1, CINC-3, ICAM-1, and IL-6 levels and plasma ALT concentrations. These parameters were significantly improved in the sirtinol-treated rats subjected to trauma-hemorrhage. Conclusion: The salutary effects of sirtinol administration on attenuation of hepatic injury following trauma-hemorrhage are, at least in part, related to reduction of pro-inflammatory mediators. [source] Nerve growth factor and gastric hyperalgesia in the ratNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2003K. Lamb Abstract We recently demonstrated an association between the development of hyperalgesia and an increase in nerve growth factor (NGF) during gastric inflammation. We hypothesized that block of NGF signalling will blunt injury-induced hyperalgesia. Male Sprague,Dawley rats (300,400 g) were anaesthetized, the stomach was exposed and placed in a circular clamp. Acetic acid (60%) or saline (control) was injected into this area and aspirated 45 s later, resulting in kissing ulcers. A balloon was surgically placed into the stomach and electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. Animals received a daily injection of neutralizing NGF antibody or control serum for 5 days. NGF in the stomach wall was measured with an ELISA. The severity of gastric injury was assessed macroscopically and by determination of myeloperoxidase (MPO) activity. Gastric injury enhanced the visceromotor response to GD and increased NGF content. Anti-NGF significantly blunted the development of hyperalgesia and led to a decrease in gastric wall thickness and MPO activity. Increases in NGF contribute to the development of hyperalgesia after gastric injury. This may be partly mediated by direct effects on afferent nerves and indirectly by modulatory effects on the inflammatory response. [source] Betulinic acid protects against ischemia/reperfusion-induced renal damage and inhibits leukocyte apoptosisPHYTOTHERAPY RESEARCH, Issue 3 2010Emel Ek, lu-Demiralp Abstract The possible protective effect of betulinic acid on renal ischemia/reperfusion (I/R) injury was studied. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Betulinic acid (250 mg/kg, i.p.) or saline was administered at 30 min prior to ischemia and immediately before the reperfusion. Creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and TNF-, as well as the oxidative burst of neutrophil and leukocyte apoptosis were assayed in blood samples. Malondialdehyde (MDA), glutathione (GSH) levels, Na+, K+ -ATPase and myeloperoxidase (MPO) activities were determined in kidney tissue which was also analysed microscopically. I/R caused significant increases in blood creatinine, BUN, LDH and TNF-,. In the kidney samples of the I/R group, MDA levels and MPO activity were increased significantly, however, GSH levels and Na+, K+ -ATPase activity were decreased. Betulinic acid ameliorated the oxidative burst response to both formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA) stimuli, normalized the apoptotic response and most of the biochemical indices as well as histopathological alterations induced by I/R. In conclusion, these data suggest that betulinic acid attenuates I/R-induced oxidant responses, improved microscopic damage and renal function by regulating the apoptotic function of leukocytes and inhibiting neutrophil infiltration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Therapeutic efficacy of pycnogenol in experimental inflammatory bowel diseasesPHYTOTHERAPY RESEARCH, Issue 12 2004Miyako Mochizuki Abstract Pycnogenol was administered for 10 days by gavage to Sprague-Dawley rats fed an elemental diet, then inflammatory bowel disease (IBD) was induced by intrarectal administration of ethanol 2,4,6-trinitrobenzene sulfonic acid (TNBS). Twelve hours after TNBS treatment, the rats were killed, the colon was assessed by a macroscopic damage score and mucosa homogenate was assayed for myeloperoxidase (MPO) activity. The supplementation of pycnogenol significantly inhibited the macroscopic damage score and MPO activity in a dose-dependent manner. These results suggested that pycnogenol ameliorates TNBS-induced inflammation by radical scavenging activity, and may have beneficial effects as a supplement in enteral nutrition for IBD. Copyright © 2004 John Wiley & Sons, Ltd. [source] Electroporation-mediated interleukin-10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allograftsTHE JOURNAL OF GENE MEDICINE, Issue 2 2006Reza Tavakoli Abstract Objectives Human interleukin 10 (hIL-10) may reduce acute rejection after organ transplantation. Our previous data shows that electroporation-mediated transfer of plasmid DNA to peripheral muscle enhances gene transduction dramatically. This study was designed to investigate the effect of electroporation-mediated overexpression of hIL-10 on acute rejection of cardiac allografts in the rat. Methods The study was designed to evaluate the effect of hIL-10 gene transfer on (a) early rejection pattern and (b) graft survival. Gene transfer was achieved by intramuscular (i.m.) injection into the tibialis anterior muscle of Fischer (F344) male recipients followed by electroporation 24 h prior to transplantation. Heterotopic cardiac transplantation was performed from male Brown Norway rat to F344. Four groups were studied (n = 6). Treated animals in groups B1 and B2 received 2.5 µg of pCIK hIL-10 and control animals in groups A1 and A2 distilled water. Graft function was assessed by daily palpation. Animals from group A1 were sacrificed at the cessation of the heart beat of the graft and those in group B1 were sacrificed at day 7; blood was taken for ELISA measurement of hIL-10 and tissue for myeloperoxidase (MPO) measurement and histological assessment. To evaluate graft survival, groups A2 and B2 were sacrificed at cessation of the heart beat of the graft. Results Histological examination revealed severe rejection (IIIB-IV) in group A1 in contrast to low to moderate rejection (IA-IIIA) in group B1 (p = 0.02). MPO activity was significantly lower in group B1 compared to group A1 (18 ± 7 vs. 32 ± 14 mU/mg protein, p = 0.05). Serum hIL-10 levels were 46 ± 13 pg/ml in group B1 vs. 0 pg/ml in group A1. At day 7 all heart allografts in the treated groups B1 and B2 were beating, whereas they stopped beating at 5 ± 2 days in groups A1 and A2 vs. 14 ± 2 days in group B2 (p = 0.0012). Conclusions Electroporation-mediated intramuscular overexpression of hIL-10 reduces acute rejection and improves survival of heterotopic heart allografts in rats. This study demonstrates that peripheral overexpression of specific genes in skeletal muscle may reduce acute rejection after whole organ transplantation. Copyright © 2006 John Wiley & Sons, Ltd. [source] Glial-derived neurotrophic factor regulates intestinal epithelial barrier function and inflammation and is therapeutic for murine colitis,THE JOURNAL OF PATHOLOGY, Issue 2 2010Dei Kui Zhang Abstract Although enteric glial cells (EGCs) have been demonstrated to play a key role in maintaining intestinal epithelial barrier integrity, it is not known how EGCs regulate this integrity. We therefore hypothesized that glial-derived neurotrophic factor (GDNF) produced by EGCs might be involved in this regulation. Here we investigated the role of GDNF in regulating epithelial barrier function in vivo. Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by dextran sulphate sodium (DSS). The disease activity index (DAI) and histological score were measured. Epithelial permeability was assayed using Evans blue dye. The anti-apoptotic potency of GDNF in vivo was evaluated. The expression of tumour necrosis factor- , (TNF- ,), interleukin-1, (IL-1,), and myeloperoxidase (MPO) activity were measured by ELISA assay and/or RT-PCR. The expression of ZO-1, Akt, caspase-3, and NF- ,B p65 was analysed by western blot assay. Our results showed that GDNF resulted in a significant reduction in enhanced permeability, inhibited MPO activity, IL-1, and TNF- , expression, and increased ZO-1 and Akt expression. Moreover, GDNF strongly prevented apoptosis in vivo and significantly ameliorated experimental colitis. Our findings indicate that GDNF participates directly in restoring epithelial barrier function in vivo via reduction of increased epithelial permeability and inhibition of mucosal inflammatory response, and is efficacious in DSS-induced colitis. These findings support the notion that EGCs are able to regulate intestinal epithelial barrier integrity indirectly via their release of GDNF in vivo. GDNF is namely an important mediator of the cross-talk between EGCs and mucosal epithelial cells. GDNF may be a useful therapeutic approach to the treatment of inflammatory bowel disease. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Role of mast cells in the development of pancreatitis-induced multiple organ dysfunctionBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2002M. Dib Background: Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP). Methods: AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured. Results: The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0·05), decreased the release of histamine at 1 h (P < 0·05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0·05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation. Conclusion: Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction. © 2002 British Journal of Surgery Society Ltd [source] Glutamine attenuates hyperoxia-induced acute lung injury in miceCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1 2010Wann-Cherng Perng Summary 1.,Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo. 2.,Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored. 3.,Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-, and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice. 4.,In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia. 5.,The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival. [source] | ||||||||||||||||||||||||||||