Differentially expressed miRNAs associated with generalized aggressive periodontitis.

OBJECTIVE: This study aimed to investigate miRNA expression profiles in individuals with periodontitis which is a chronic inflammatory condition affecting the integrity of the periodontal attachment. miRNAs play a crucial role in gene regulation through various mechanisms, making them potential diagnostic markers and therapeutic targets for various diseases. MATERIALS AND METHODS: A total of 25 individuals with aggressive periodontitis and 25 controls were included in the study. Gingival tissues were collected for miRNA isolation and cDNA synthesis. miRNAs associated with periodontitis, including hsa-miR-185-5p, hsa-miR-17, hs-miR-146a, hs-miR-146b, hs-miR-155, hs-miR-203, hs-miR-205, hs-miR-223, and hsa-miR-21-3p, were analyzed using a combination of miRTarBase database analysis and literature mining was performed. Real-time PCR was used to assess the expression patterns of the target miRNAs, and the data were analyzed using the REST program. RESULTS: The study revealed upregulated expression levels of hsa-miR-223-3p, hsa-miR-203b-5p, hsa-miR-146a-5p, hsa-miR-146b-5p, and hsa-miR-155-5p in individuals with periodontitis. Conversely, downregulated expression was observed for hsa-miR-185-5p, hsa-miR-21-3p, and hsa-miR-17-3p. CONCLUSION: The findings suggest significant differences in the expression of specific miRNAs associated with inflammation in periodontitis. MZB1 acts as a hormone-regulated adipokine/pro-inflammatory cytokine, driving chronic inflammation and influencing cellular expansion. Predominantly expressed in marginal zone and B1 B cells, specialized subsets that respond rapidly to infections, MZB1 impacts immune protein synthesis and immune cell maturation, notably targeting microRNA-185 to potentially impede T cell development. Further research is needed to elucidate the functional significance and potential implications of these miRNAs. CLINICAL RELEVANCE: miRNAs regulate the expression of target genes by finely tuning protein expression levels. The current findings provide compelling evidence of notable variations in the expression levels of specific miRNAs associated with inflammation in individuals affected by periodontitis; hence, miRNAs hold promise as potential therapeutic targets for periodontitis.

Altered expression of MZB1 in periodontitis: A possible link to disease pathogenesis.

BACKGROUND: Our previous study explored the molecular signatures of generalized aggressive periodontitis (GAgP) using gingival tissues through omics-based-whole-genome transcriptomic analysis. This continuation study aimed to investigate the whole protein profiling of these gingival samples through liquid chromatography-mass spectroscopy/mass spectroscopy (LC-MS/MS) analysis and to validate the identified proteins through immunohistochemistry to provide further evidence for the quality of the results. METHODS: In previous study, gene expression patterns were identified in gingival tissues from 23 GAgP and 25 control individuals. In the current study, comparative proteomic analysis was performed on isolated proteins from the same study groups using LC-MS/MS analysis. The data from the transcriptomics study published before and the proteomics data were integrated to reveal any common genes and proteins. Additionally, immunohistochemical analysis was conducted to further investigate the findings. RESULTS: The most upregulated proteins in patients compared to controls were ITGAM, AZU1, MMP9, BPI, UGGG1, MZB1, TRFL, PDIA6, PRDX4, and PLG. The top six pathways associated with these proteins were involved in innate immune system, post-translational protein phosphorylation, interleukin-4 and -13 signaling, toll-like receptors cascades, and extracellular matrix organization. Based on the integration and validation analysis of transcriptomics and proteomics data, as well as immunohistochemical analysis, MZB1 was identified as a shared gene and protein that were upregulated in the patients. CONCLUSIONS: MZB1 is a protein that is involved in the development of B cells and the production of antibodies. Its upregulation in periodontitis suggests that there may be a dysregulation of the immune response in this condition, and MZB1 may be a potent biomarker for periodontitis.

The apelin-apela receptor APJ is necessary for formation and healing of ischemia reperfusion-induced gastric ulcer in rats.

The apelinergic system widely expressed and regulates hormone-enzyme secretion, motility, and protective mechanisms of the stomach. This system consists of the apelin receptor (APJ) and two peptides known as apela and apelin. The IR-induced experimental gastric ulcer model is a well-known and commonly used one that induces hypoxia and causes the release of proinflammatory cytokines. Expressions of apelin and its receptor APJ are induced by hypoxia and inflammation in the gastrointestinal tract. Apelin has been shown to affect angiogenesis positively, considered the most critical component of the healing process. Although it is known that apelin and AJP expressions are induced by inflammatory stimuli and hypoxia, stimulate endothelial cell proliferation and have a role in regenerative angiogenesis, no information or has been found in the literature regarding the role of APJ in the formation and healing of gastric mucosal lesions induced by I/R. So, we conducted a study to clarify the role of APJ in formation and healing mechanisms of IR-induced gastric lesions. Male Wistar rats were divided into five groups; control, sham-operated, IR, APJ antagonist treated-IR group (F13A+IR), and the healing groups. F13A was intravenously given to the animals. Gastric lesion index, mucosal blood flow, PGE2, NOx, 4-HNE-MDA, HO activity, and protein expressions of VEGF and HO-1 were measured. F13A application before the IR increased the mucosal injury, F13A application following the ischemia delayed the mucosal healing during the reperfusion period. Consequently, blocking apelin receptors may worsen gastric injury due to the IR and delay mucosal healing.

Analysing the effect of sodium bicarbonate and glycine air polishing on tooth surfaces with two different imaging methods.

The aim of this study was to compare two different imaging methods by assessing changes caused by sodium bicarbonate and glycine air polishing on the tooth surfaces. Fourteen single root teeth with exposed root surfaces were included into the study. The teeth were randomly divided into two groups: sodium bicarbonate and glycine group. Samples were scanned in a micro-computed tomography (micro-CT) and CAD/CAM (computer-aided design/computer-aided manufacturing) at baseline and then after air-polishing powder applications, the defect volume values were evaluated. There was a statistically significant difference between mean defect volume values that occurred after glycine and sodium bicarbonate air polishing evaluated with micro-CT and CAD/CAM (p < 0.05). After sodium bicarbonate air polishing, defect volume on enamel surface at maximum power and defect volume on the exposed root surface at medium power values calculated with CAD/CAM were higher. After glycine air polishing, defect volume values on both surfaces at medium power setting calculated with CAD/CAM were lower. Defect volume values on enamel surface at maximum power setting calculated with CAD/CAM were higher than calculated with micro-CT. We concluded that CAD/CAM cannot provide as accurate results as micro-CT. Glycine-based powder is less abrasive than sodium bicarbonate, especially on enamel surface. Lay Description: Micro-CT is a non-destructive imaging method with high resolution and allows to examine all tooth structures individually. CAD/CAM are systems that are widely used in dentistry today. Access to the device is easier than micro-CT. Intraoral scanners in CAD/CAM systems also provide non-destructive image scanning. The aim of this study was to compare two different imaging methods by assessing changes caused by sodium bicarbonate and glycine air polishing on the tooth surfaces. The results showed that because of the analyses made with CAD/CAM, similar results could not be obtained with micro-CT and cannot be used to evaluate the changes that occur after air polishing.

Expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) in mouse uterus during the peri-implantation period.

Nuclear factor-erythroid 2-related factor- 2 (Nrf2) is a nuclear transcription factor that facilitates transcription of genes for detoxification enzymes and antioxidant proteins. We investigated the distribution and expression of Nrf2 during the peri-implantation period. We detected Nrf2 in uteri of mice during estrus (control) and on days 1, 4, 5, 6 and 8 of pregnancy using immunohistochemistry, quantitative real-time polymerase chain reaction and western blotting. Nrf2 immunostaining was significantly greater on days 1, 5 and 6 of pregnancy compared to controls, and on days 4 and 8 of pregnancy; western blotting results were consistent with immunohistochemical observations. Nrf2 mRNA levels on days 5 and 8 were significantly higher than for control uteri. Increased expression of Nrf2 on days 1, 5 and 6 of pregnancy may be important for uterine receptivity, implantation and decidualization by protecting the developing embryo and uterus from the adverse effects of oxidative stress.

Protective effects of apelin on gastric mucosa.

The apelin/APJ system, which has a widespread distribution in the body, is involved in the regulation of physiological and pathophysiological mechanisms such as regulation of blood pressure, stress response, immunological activities, obesity, diabetes, inflammation, and neurodegenerative diseases. Apelin also undertakes various tasks in the digestive system such as cell proliferation, secretion of hormones (eg. cholecystokinin and histamine), modulation of gastric and pancreatic secretions, and motility response. Recent researchs have reported that apelin exerts gastroprotective effects by regulating the components of gastric mucosal barrier. Mucosal disorders that can develop in the stomach due to different reasons such as microbial infections, drug use, smoking habits, alcohol consumption, exposure to stress, pepsin, and acid affect a significant proportion of the human population in the world. This review discusses the role of apelin in the protective mechanisms of gastric mucosa against harmful effects.

The effect of apelin-13 on gastric ischemia/reperfusion injury: the roles of sensory nerves and vagus nerve.

Apelin is a peptide that plays a role in physiological processes such as angiogenesis, apoptosis, and proliferation. The aim of this study was to investigate the role of capsaicin-sensitive afferent neurons and vagus in the effect of apelin against ischemia/reperfusion (I/R) injury. The experimental groups were (1) control, (2) I/R, (3) apelin + I/R, (4) vagotomy + I/R, (5) vagotomy + apelin + I/R, (6) capsaicin + I/R, (7) capsaicin + apelin + I/R, (8) lorglumide + I/R, and (9) lorglumide + apelin + I/R. To test the potential gastroprotective effect of apelin-13, apelin-13 (2 mg/kg i.v.) was administered just before both ischemia and reperfusion. A vagotomy was performed 1 week before I/R in the vagotomized groups; capsaicin (125 mg/kg s.c.) was administrated 2 weeks before I/R in the capsaicin-treated groups and lorglumide (5 mg/kg i.p.) was administered 30 min before I/R in the lorglumide-treated groups. After I/R, a variety parameters in gastric tissue were analyzed. cfos expression was determined in brainstem samples. In the I/R group, the lesion index, myeloperoxidase activity, lipid peroxidation, nitric oxide, and tumor necrosis factor-α increased, and mucosal blood flow, prostaglandin-E2, and calcitonin gene related peptide decreased. Apelin prevented the damaging effects of I/R and increased cfos expression in brainstem areas. Vagotomy, capsaicin, and lorglumide largely eliminated the gastroprotective effects of apelin-13. This study showed that sensory nerves and the vagus play regulatory roles in apelin-induced gastroprotection. Cholecystokinin may play a role in the effect of apelin through sensory neurons.

The effect of docosahexaenoic acid on apelin distribution of nervous system in the experimental mouse model of Parkinson's disease.

Parkinson's disease (PD) is a degenerative disorder of the human central and peripheral nervous systems. n-3 fatty acids docosahexaenoic acid (DHA, C22: 6n-3) and eicosapentaenoic acid (EPA) as well as apelin have anti-inflammatory effects in various cells. At the same time, apelin has anti-oxidative and anti-apoptotic effects. The study was conducted to determine the effect of DHA on the distribution of apelin and apelin receptor (APJ) in the central nervous system in 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-induced PD model. DHA treatment decreased the return time and total down time in the Parkinson group which were measured by pole test. Besides, the ambulatory activity, distance and total locomotor activity were increased by DHA in the PD model of animals. The time mice remained on the rotating rod mile was also significantly increased by DHA treatment in MPTP injected animals. The apelin expression in the pons of mice in the Parkinson, DHA and Parkinson + DHA groups were lower compared to the Control group. When apelin and apelin receptor expressions in cerebrum were examined, there was no statistically significant difference between the groups. When apelin receptor expression in cerebellum was examined, the difference between the Control and Parkinson + DHA, Parkinson and Parkinson + DHA, DHA and Parkinson + DHA groups were statistically significant. Apelin receptor expressions in pons of the Parkinson, DHA and Parkinson + DHA groups were lower compared to the Control group. Apelin protein levels of cerebellum and pons were found to be decreased in DHA group compare with Control group. In conclusion; DHA has been implicated in the expression of the apelin receptor and has reduced the expression of APJ receptor.

Peripheral apelin mediates stress-induced alterations in gastrointestinal motor functions depending on the nutritional status.

Exposure to stress induces gastrointestinal (GI) dysmotility. In rodents, acute restraint stress (ARS) inhibits gastric emptying (GE) and intestinal transit (IT) via central and peripheral corticotropin-releasing factor (CRF)-mediated pathways. Peripherally administered apelin-13 was shown to inhibit GI motor functions; moreover, stress-induced upregulation of gastric apelin content was demonstrated in rats suggesting that peripheral apelin may mediate stress-induced alterations in GI motility. We investigated the role of endogenous peripheral apelin in stress-induced GI dysfunction. GE, IT and gastro-duodenal fasting motility were measured in non-stressed (NS), CRF-injected and ARS-loaded rats. CRF and apelin receptor antagonists astressin or F13A was administered before ARS or peripheral CRF injection. Apelin and APJ receptor expressions were determined using immunohistochemistry and quantified by qRT-PCR. Double immunofluorescence was performed for enteric neuronal apelin. GE and IT were delayed by CRF and ARS. ARS-induced changes were attenuated by F13A, whereas astressin was ineffective. CRF-induced alterations in GE and IT were restored completely by astressin, while they were diminished by F13A. Antral phase III-like contractions were disturbed following ARS which were preserved by preadministration of astressin, but not F13A. CRF impaired gastric and duodenal fasting contractions, while these changes were not altered by F13A. ARS increased apelin expression in stomach and duodenum. Apelin immunoreactivity was detected in mucosa, smooth muscles and myenteric plexi, whereas dense APJ receptor expression was observed within tunica muscularis. APJ receptor was downregulated in rats fasted overnight. These results suggest that enteric apelin acts as an inhibitor stress mediator in the postprandial state.

The effect of apelin on the functions of peritoneal macrophages.

Apelin, the endogenous ligand of the G protein-coupled receptor (APJ), plays an important role in the physiological response to homeostatic perturbations. The aim of the present study was to investigate the effect of apelin on the functions of peritoneal macrophages. A double staining immunofluorescence technique was used to determine the expression of APJ in peritoneal macrophages. Rat peritoneal macrophages were randomly divided into three groups: control, apelin and apelin+F13A. A significant decrease in phagocytic and chemotactic activity of peritoneal macrophages resulted when the macrophages were incubated with [Pry(1)]-Apelin-13 (10 ng/ml). Incubation of peritoneal macrophages with the APJ receptor antagonist, F13A (20 ng/ml) prevented the suppressive effect of apelin on phagocytosis and chemotaxis. Peritoneal macrophages incubated with [Pry(1)]-Apelin-13 exhibited a decrease in the production of TNF-alpha and IL-6 compared to the control macrophages. Incubation of peritoneal macrophages with [Pry(1)]-Apelin-13 plus F13A prevented the decrease in the production of proinflammatory cytokines produced by [Pry(1)]-Apelin-13. In conclusion, apelin may be a mediator that inhibits the functions of activated macrophages.

The role of apelin in the healing of water-immersion and restraint stress-induced gastric damage.

The objective of this study was to explore the role of apelin in the healing of gastric lesions induced by stress. Male Wistar rats were exposed to water immersion and restraint stress (WIRS) for 6 h with or without the apelin receptor antagonist F13A. The rats were killed on the 1st, 3rd, 5th or 10th day after the end of stress induction. Apelin and hypoxia-inducible factor-1α expression was increased on the 1st day after the end of stress exposure and was decreased daily thereafter. However, F13A retarded the healing of gastric lesions by preventing the improvement of mucosal blood flow, prostaglandin E2 production and vascular endothelial growth factor expression in rats exposed to WIRS. Additionally, F13A increased the gastric 4-hydroxynonenol + malondialdehyde content on the 1st and 3rd days after the end of stress induction but did not affect the change in gastric mucosal nitric oxide levels. In conclusion, apelin may be a regulatory protein involved in the healing mechanism of stress-induced gastric damage.

Opposite effects of central oxytocin and arginine vasopressin on changes in gastric motor function induced by chronic stress.

Hypothalamic oxytocin (OXT) and arginine vasopressin (AVP) are known to act oppositely on hypothalamic-pituitary-adrenal (HPA) axis, stress response and gastrointestinal (GI) motility. In rodents, exposure to restraint stress (RS) delays gastric emptying (GE), however, repeated exposure to the same stressor (chronic homotypic stress (CHS)), the delayed GE is restored to basal level, while hypothalamic OXT is upregulated. In contrast, when rats are exposed to chronic heterotypic stress (CHeS), these adaptive changes are not observed. Although the involvement of central OXT in gastric motor adaptation is partly investigated, the role of hypothalamic AVP in CHeS-induced maladaptive paradigm is poorly understood. Using in-vivo brain microdialysis in rats, the changes OXT and AVP release from hypothalamus were monitored under basal non-stressed (NS) conditions and in rats exposed to acute stress (AS), CHS and CHeS. To investigate the involvement of central endogenous OXT or AVP in CHS-induced habituation and CHeS-induced maladaptation, chronic central administration of selective OXT receptor antagonist L-371257 and selective AVP V1b receptor antagonist SSR-149415 was performed daily. OXT was measured higher in AS and CHS group, but not in CHeS-loaded rats, whereas AVP significantly increased in rats exposed to AS and CHeS. Additionally, the response of the hypothalamic OXT- and AVP-producing cells was amplified following CHS and CHeS, respectively. In rats exposed to AS for 90min solid GE significantly delayed. The delayed-GE was completely restored to the basal level following CHS, however, it remained delayed in CHeS-loaded rats. The CHS-induced restoration was prevented by L-371257, whereas SSR-149415 abolished the CHeS-induced impaired GE. A significant correlation was observed between GE and (i) OXT in CHS-loaded rats (rho=0.61, p<0.05, positively), (ii) AVP in CHeS-loaded rats (rho=0.69, p<0.05, negatively). Under long term stressed conditions, the release of AVP and OXT from hypothalamus may vary depending on the content of the stressors. Central AVP appears to act oppositely to OXT by mediating CHeS-induced gastric motor maladaptation. Long term central AVP antagonism might be a pharmacological approach for the treatment of stress-related gastric motility disorders.

Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.

Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway.

Gastroprotective effect of orexin-A and heme oxygenase system.

BACKGROUND: Orexin-A, besides playing an important role in the mechanism of food intake, exhibits a potent gastroprotective action against the formation of acute gastric mucosal injury. The aim of the present study was to determine the effect of administered orexin-A against ischemia-reperfusion (I/R)-induced gastric injury on the expression of heme oxygenase (HO)-1 and HO-2 in gastric tissue. MATERIALS AND METHODS: Wistar rats were subjected to 30 min of ischemia followed by 3 h reperfusion. Orexin-A was infused at a dose of 500 pmol/kg/min during the I/R period. The lesion area was measured by stereomicroscope. The myeloperoxidase activity and 4-hydroxinonenol-malondialdehyde content of gastric mucosa were evaluated spectrophotometrically, and the gastric tumor necrosis factor-α was measured by enzyme linked immune sorbent assay. The expression of HO-1 and HO-2 was determined by Western blotting analysis. RESULTS: Orexin-A significantly decreased the I/R-induced gastric lesions, myeloperoxidase activity, and 4-hydroxinonenol-malondialdehyde concentration in gastric tissue exposed to I/R. The gastroprotective effect of orexin-A in gastric I/R model was accompanied by the increase in HO-2 expression and the decrease in HO-1 expression. CONCLUSIONS: Orexin-A exerts a protective action on gastric mucosa subjected to I/R, and this effect is associated with the reduction of neutrophil infiltration and lipid peroxidation in gastric tissue in addition to the increase in HO-2 expression due to the administration of orexin-A.

The protective effect of apelin against water-immersion and restraint stress-induced gastric damage.

The aim of the present study was to investigate the gastroprotective effect of apelin on water-immersion and restraint stress (WIRS)-induced gastric lesions. Male Wistar rats were divided into four groups: control, WIRS, F13A + WIRS and F13A. APJ receptor antagonist F13A was administered to rats to determine the influence of apelin on stress-induced gastric injury. WIRS administered for 6 h resulted in the development of gastric mucosal lesions accompanied by a significant increase in plasma corticosterone. WIRS increased the concentration of 4-hydroxynonenol (4-HNE) + malondialdehyde (MDA) and the expression of apelin and hypoxia inducible factor-1α (HIF-1α) in gastric mucosa. In addition, WIRS reduced the mucosal blood flow and gastric prostaglandin E(2) (PGE(2)) concentration. Plasma corticosterone, which was increased due to stress, was significantly decreased in the F13A + WIRS group. Gastric lesions and the 4-HNE + MDA concentration were also higher in the F13A + WIRS compared to the WIRS group. We conclude that apelin has a gastroprotective effect against stress-induced lesions possibly by reducing lipid peroxidation in gastric mucosa.

Effect of orexin-A on phagocytic activity of peritoneal macrophage in starved rats.

The aim of this study was to investigate the effect of fasting-induced orexin-A (OXA) on inflammation and macrophage phagocytic activity. Fifty six male wistar rats were fasted for 36 h to stimulate OXA synthesis. In 24 rats, air pouches were induced subcutaneously in the intrascapular area. After (6 h) carrageenan injection into the pouches, the contents of the air pouches were removed. The exudate volume, protein content and cell count were measured. After the determination of fasting on inflammation, the peritoneal macrophages were collected from 32 rats to investigate the effect of fasting-induced OXA on macrophage phagocytic activity. Plasma OXA levels were markedly higher in fasted rats compared with control rats. The phagocytic capability of peritoneal macrophages was obtained as a percentage of phagocytosing macrophages and number of phagocytosed particles per cell. In spite of increased blood OXA level SB-334867, selective orexin type 1 receptor antagonist (10 mg/kg) did not change phagocytic activity of peritoneal macrophages. These findings indicate that 36 h fasting-induced OXA has no significant effect to phagocytosis of peritoneal macrophages.

Endogenous orexin-A modulates gastric motility by peripheral mechanisms in rats.

Orexin-A (OXA) and orexin receptor type 1 (OX1R) are found in enteric nervous system and smooth muscle cells in the digestive tract. Fasting is a stimulant for OXA synthesis. The aim of the present study was to investigate central and peripheral effects of endogenous OXA on gastric motility. Endogenous OXA synthesis was induced by 36h fasting. Vagotomy was used to evaluate N.vagus-mediated effects of OXA. Gastric emptying and interdigestive gastric motility were measured by spectrophotometric and manometric methods, respectively. Rats were pretreated with OX1R antagonist SB-334867 prior to measurements. Plasma OXA concentration was assayed with radioimmunoassay while preproorexin (PPO) expression was determined with Western blotting in gastric and hypothalamic tissues. OXA immunoreactivity in antrum was determined with immunohistochemistry. Plasma OXA level, PPO protein expression and OXA immunoreactivity were significantly increased in response to 36h fasting. Endogenous OXA facilitated gastric emptying and inhibited gastric interdigestive motility. As these effects were abolished with SB-334867, it is likely that gastrokinetic effects of OXA are mediated via OX1R. Vagotomy did not alter OXA-mediated effects. According to current data, OXA is up-regulated both centrally and peripherally upon fasting. Endogenous OXA accelerates gastric emptying while it inhibits interdigestive motility.

Expressions of inducible nitric oxide synthase and cyclooxygenase-2 in gastric ischemia-reperfusion: role of angiotensin II.

BACKGROUND: Angiotensin II contributes to the pathogenesis of inflammation induced by ischemia-reperfusion (I/R) in various organs. Angiotensin II increases vascular permeability that initiates the inflammatory process and leads to the migration of inflammatory cells into the tissue. The aim of the present study was to investigate the effect of angiotensin II on ischemia-reperfusion induced expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat stomachs exposed to ischemia-reperfusion. METHODS: Wistar rats were randomly separated into five groups: sham operated, I/R, I/R plus candesartan (an AT1 receptor antagonist), I/R plus PD123319 (an AT2 receptor antagonist), and I/R plus captopril (an angiotensin-converting enzyme inhibitor). Candesartan (1mg/kg/d), PD123319 (3mg/kg/d), and captopril (20mg/kg/d) were given subcutaneously twice a day for 5 d before I/R. The rats were submitted to gastric ischemia by clamping the celiac artery for 30min followed by 24h reperfusion. RESULTS: Candesartan decreased the neutrophil accumulation, iNOS expression, and increased NOx level, COX-2 expression in the gastric tissue exposed to I/R compared with I/R group. PD123319 did not change the neutrophil accumulation, iNOS expression, PGE(2), or NOx levels, but increased the expression of COX-2 in the gastric tissue exposed to I/R. However, captopril did not play any role in I/R induced change in gastric mucosa. CONCLUSIONS: The results suggest that Angiotensin II via angiotensin II type 1 receptor increases the accumulation of neutrophils and iNOS expression and plays a significant role in mediating inflammation in gastric mucosa exposed to I/R.

Effect of orexin-a on ischemia-reperfusion-induced gastric damage in rats.

BACKGROUND: Orexins are involved in the regulation of sleeping behavior and energy homeostasis, and they are also implicated in the regulation of gastrointestinal functions. Previous reports have demonstrated the expression of orexin receptors in the gastrointestinal system. The aim of this study was to investigate the gastroprotective effect of orexin-A in ischemia-reperfusion-induced gastric mucosal injury. METHODS: The gastric ischemia-reperfusion model was established by clamping the celiac artery for 30 min and reperfusing for 60 min. Orexin-A was administered in doses of 500 pmol.kg(-1).min(-1) by infusion throughout the ischemia-reperfusion period. The mean lesion area, gastric prostaglandin E2 and mucus content, myeloperoxidase activity, and production of thiobarbituric acid reactive substances were measured. RESULTS: Orexin-A significantly attenuated the ischemia-reperfusion-induced gastric lesions and also decreased myeloperoxidase activity and the thiobarbituric acid reactive substances content in gastric mucosa of rats exposed to ischemia-reperfusion. However, the decline in gastric prostaglandin E2 and mucus content was not restored by orexin-A treatment. CONCLUSIONS: Orexin-A exhibited a gastroprotective effect against ischemia-reperfusion-induced lesions by decreasing neutrophil activation and lipid peroxidation.

Effect of docosahexaenoic acid on macrophage functions of rats.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid which has been demonstrated to exhibit anti-inflammatory effects. The objective of this study was to determine the effect of DHA on phagocytic and chemotactic activities of peritoneal macrophages obtained from rats. DHA was dissolved in 1 ml of corn oil at dose of 36 mg/kg/day and given via oral gavage for 4 weeks. Control rats received 1 ml/day corn oil as vehicle. At the end of the treatment period, peritoneal macrophages were isolated and chemotactic and phagocytic activities were assayed. Chemotactic and phagocytic activities were reduced in rats fed with DHA. These results demonstrated the effect of DHA in modulating immune activities of rat peritoneal macrophages.