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.

The effect of maternal period nutritional status on oro-sensorial fat perception and taste preference in rats.

CD36 and GPR120 play an important role in the perception and preference for fat-rich food consumption. We aimed to investigate the relationship between oro-gustatory perception of lipids, fatty taste preference, and maternal (Gestation + Lactation)-maturation period nutrition status in offspring Sprague-Dawley rats. In our study, mother rats were fed with control (C) or high-fat diets (HFD) during gestation (21 days) and lactation (21 days) periods. After weaning, the offspring were fed with control (C) or high-fat diets (HFD) during the maturation (120 days) period. Daily calorie intake and weekly body weight measurements were monitored. Two-bottle preference (TBPT) and licking tests measured the fat perceptions and preferences. Plasma levels of insulin, leptin, glucose, and triglyceride were measured. The protein and mRNA expressions of CD36 and GPR120 in the circumvallate papillae (CVP) were determined. The 48 h TBPT results revealed that maternal HFD-exposed offspring rats significantly preferred 2% rapeseed oil solution regardless of the type of maturation diet. According to the licking test, C/C group (C diet exposed group in maternal and maturation periods) offspring licked 0.1% oleic acid-containing water more than C/HFD (C diet exposed in maternal period and HFD exposed group in maturation period) and HFD/HFD group. (HFD exposed group in maternal and maturation periods) groups. Plasma insulin and leptin concentrations significantly increased in HFD/HFD groups compared to C/C group. CD36 protein expressions were significantly lower in HFD/HFD than C/HFD and HFD/C groups. GPR120 and GNAT3 mRNA expressions in HFD/C group were significantly higher than in C/HFD group. Our results suggest that HFD exposure during maternal and maturation period may play a role in fat perception/preference through oral lipid sensors.

Combinatorial effects of melatonin and paclitaxel differ depending on the treatment scheme in colorectal cancer in vitro.

AIMS: Colorectal carcinoma (CRC) is the third most prevalent cancer with high mortality. Besides regulating the circadian rhythm, melatonin (MTN) exerts anticancer activities. Paclitaxel (PTX) is successful against different malignancies, however, acquired resistance and variability in patient response restrict its use. mTOR and MAPK pathways are often deregulated in human cancers. We aimed to investigate whether MTN enhances or sensitizes the chemotherapeutic activity of PTX and if so, determine the underlying possible mechanisms in CRC in vitro. MAIN METHODS: Antiproliferative and cytotoxic activities of PTX and MTN were assessed alone and in combination, as well as with different treatment regimens (renewal or replacement of the treatment after 24 h), up to 48 h. Apoptosis, viability and autophagy were assessed by flow cytometry. mTOR and MAPK pathway activities were investigated by immunoblotting. KEY FINDINGS: Both drugs reduced cell viability in a dose-dependent manner at 24 and 48 h. Only the highest dose of MTN (500 µM) potentiated the cytotoxicity of PTX (50 nM). Replacement of PTX after 24 h with MTN was superior in reducing cell viability than vice versa via apoptosis induction. Renewal of MTN treatment every 24 h reduced autophagy compared to the control group, while other treatments did not alter the autophagic activity. A 24 h MTN treatment followed by 24 h PTX treatment increased S6 phosphorylation in a mTOR-independent manner and increased Erk1/2 phosphorylation. SIGNIFICANCE: The present study suggests that sequential treatment with MTN and PTX distinctly affect apoptosis and cytotoxicity via regulating mTOR and MAPK pathways differentially in CRC.

Investigation of obesogenic effects of hexachlorobenzene, DDT and DDE in male rats.

Obesity has become a very important public health problem and is increasing globally. Genetics, individual and environmental factors play roles in the etiology of this complex disorder. Recently, several environmental pollutants have been suggested to have obesogenic activities. Peroxisome proliferator activating receptor gamma (PPARγ), uncoupling protein-1 (UCP1) and their expression in white adipose tissue (WAT) and brown adipose tissue (BAT) play key roles in adipogenesis. UCP3 and irisin were reported to play roles in non-shivering thermogenesis. Our primary aim was to investigate obesogenic effects of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in rats. In addition, thermoregulatory effects of HCB, DDT and DDE were also investigated by analyzing the levels of Ucp3 and irisin. Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups as control, HCB, DDT and DDE. Animals were administered with organochlorine pesticides (OCPs; 5 mg/kg bw) by oral gavage every other day for five weeks. At the end of the experimental period, the animals were sacrificed, BAT and WAT samples were collected to analyze Pparγ, Ucp1 and Ucp3 levels. Moreover, skeletal muscle samples were collected to examine Ucp3 and irisin levels. Serum glucose, cholesterol and triglyceride levels were also determined. Body weight and core temperature of the animals were not significantly affected by any of the OCP administration. Serum glucose, cholesterol and triglyceride levels were similar among the experimental groups. Pparγ expression was significantly elevated by HCB administration only in WAT (p < 0.05). On the other hand, both Pparγ and Ucp1 expressions were diminished in WAT and BAT (p < 0.01) by DDT treatment, while in WAT, DDE significantly decreased Pparγ expression without altering its expression in BAT (p < 0.001). Ucp3 and irisin levels in skeletal muscle were not altered. Our findings show that both DDT and DDE reduce the browning of WAT by suppressing white adipocytes and thus may have obesogenic activity in male rats without altering thermoregulation. In addition, HCB, DDT and DDE-induced alterations in expression of Pparγ and Ucp1 in WAT implicates differential regulation of adipogenic processes.

Evaluation of body mass index and related lifestyle factors among 14-17-year-old Turkish adolescents.

OBJECTIVE: During adolescence, unhealthy body weight status is considered as a global concern as it may lead to adverse health consequences in adulthood, therefore evaluation of the risk factors is crucial. The aim of the study was to determine the prevalence of adolescents under the risk of being underweight, overweight, and obese among 14-17-year-old Turkish adolescents. In addition, we examined the association between unhealthy body weight categories and lifestyle factors. METHODS: This study was designed as cross-sectional study which included body weight status and associated parameters of 1561 adolescents aged between 14 and 17 who were registered 25 different high schools in Istanbul, Uskudar. Height and body weight of participants were measured and related factors were obtained through a questionnaire. Differences in distributions were analyzed using the Chi-square test and to control confounding factors, multivariate logistic regression analysis was performed. As statistical significance limit of p<0.05 was determined. RESULTS: Body mass index (BMI) percentile analyses indicated that 3.6% of participants were underweight, 14.3% were overweight, and 13.8% were obese. We demonstrated that age, gender, and school types were statistically very significantly associated with BMI (p<0.001) and daily meal frequency, eating speed, and mealtime regularity were significantly related with BMI (p<0.05). In addition, according to multivariate analysis results, gender and school types were closely related with obesity among 14-17-year old Turkish adolescents. CONCLUSION: This study has been demonstrated that frequency of adolescent obesity in Istanbul, Turkey, has increased and obesity closely related to gender and type of school. Further educational and interventional studies should be organized in this region with consideration of relevant risk factors.

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.

The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats.

The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.

Anti-inflammatory and cytoprotective properties of hydrogen sulfide.

Hydrogen sulfide is an endogenous gaseous mediator that plays important roles in many physiological processes in microbes, plants, and animals. This chapter focuses on the important roles of hydrogen sulfide in protecting tissues against injury, promoting the repair of damage, and downregulating the inflammatory responses. The chapter focuses largely, but not exclusively, on these roles of hydrogen sulfide in the gastrointestinal tract. Hydrogen sulfide is produced throughout the gastrointestinal tract, and it contributes to maintenance of mucosal integrity. Suppression of hydrogen sulfide synthesis renders the tissue more susceptible to injury and it impairs repair. In contrast, administration of hydrogen sulfide donors can increase resistance to injury and accelerate repair. Hydrogen sulfide synthesis is rapidly and dramatically enhanced in the gastrointestinal tract after injury is induced. These increases occur specifically at the site of tissue injury. Hydrogen sulfide also plays an important role in promoting resolution of inflammation, and restoration of normal tissue function. In recent years, these beneficial actions of hydrogen sulfide have provided the basis for development of novel hydrogen sulfide-releasing drugs. Nonsteroidal anti-inflammatory drugs that release small amounts of hydrogen sulfide are among the most advanced of the hydrogen sulfide-based drugs. Unlike the parent drugs, these modified drugs do not cause injury in the gastrointestinal tract, and do not interfere with healing of preexisting damage. Because of the increased safety profile of these drugs, they can be used in circumstances in which the toxicity of the parent drug would normally limit their use, such as in chemoprevention of cancer.

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.

H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential.

Hydrogen sulfide exerts a number of cytoprotective and anti-inflammatory effects in many organ systems. In an effort to exploit these potent and beneficial effects, a number of hydrogen sulfide-releasing derivatives of existing drugs have been developed and extensively tested in pre-clinical models. In particular, efforts have been made by several groups to develop hydrogen sulfide-releasing derivatives of a number of nonsteroidal anti-inflammatory drugs. The main goal of this approach is to reduce the gastrointestinal ulceration and bleeding caused by this class of drugs, particularly when used chronically such as in the treatment of arthritis. However, these drugs may also have utility for prevention of various types of cancer. This paper provides an overview of some of the mechanisms underlying the anti-inflammatory and cytoprotective actions of hydrogen sulfide. It also gives some examples of hydrogen sulfide-releasing anti-inflammatory drugs, and their actions in terms of reducing inflammation and attenuating the development of cancer in experimental models.

Mechanism of the beneficial effect of melatonin in experimental Parkinson's disease.

This study aimed to elucidate locomotor activity changes in 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) and investigate the possible beneficial effects of melatonin on altered levels of locomotor activity, cyclooxygenase (COX), prostaglandin E2 (PGE2), nuclear factor kappa-B (NF-κB), nitrate/nitrite and apoptosis. Male Wistar rats were divided into five groups: vehicle (V), melatonin-treated (M), 6-OHDA-injected (6-OHDA), 6-OHDA-injected + melatonin-treated (6-OHDA-Mel) and melatonin treated + 6-OHDA-injected (Mel-6-OHDA). Melatonin was administered intraperitoneally at a dose of 10 mg/kg/day for 30 days in M and Mel-6-OHDA groups, for 7 days in 6-OHDA-Mel group. Experimental PD was created stereotactically via unilateral infusion of 6-OHDA into the medial forebrain bundle (MFB). The 6-OHDA-Mel group started receiving melatonin when experimental PD was created and treatment was continued for 7 days (post-treatment). In the Mel-6-OHDA group, experimental PD was created on the 23rd day of melatonin treatment and continued for the remaining 7 days (pre- and post-treatment). Locomotor activity performance decreased in 6-OHDA group compared with vehicle; however melatonin treatment did not improve this impairment. Nuclear factor kappa Bp65 and Bcl-2 levels were significantly decreased while COX, PGE2 and caspase-3 activity were significantly increased in 6-OHDA group. Melatonin treatment significantly decreased COX, PGE2 and caspase-3 activity, increased Bcl-2 and had no effect on NF-κB levels in experimental PD. 6-Hydroxydopamine injection caused an obvious reduction in TH positive dopaminergic neuron viability as determined by immunohistochemistry. Melatonin supplementation decreased dopaminergic neuron death in 6-OHDA-Mel and Mel-6-OHDA groups compared with 6-OHDA group. Melatonin also protected against 6-OHDA-induced apoptosis, as identified by increment in Bcl-2 levels in dopaminergic neurons. The protective effect of melatonin was more prominent for most parameter following 30 days treatment (pre- and post-) than 7 days post-treatment. In summary, melatonin treatment decreased dopaminergic neuron death in experimental PD model by increasing Bcl-2 protein level and decreasing caspase-3 activity.

Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat.

A relationship has been shown between preeclampsia (PE) and intrauterine growth restriction (IUGR) and oxidative stress (OS). Since such pregnancies experience OS, we aimed to detect the distribution pattern and expression levels of a transcription factor, Nuclear factor erythroid 2-related factor-2 (Nrf2) that has a role in the regulation of antioxidant enzymes, and peroxiredoxin 6 (Prdx6) an antioxidant enzyme, in human healthy, IUGR, PE and in groups of rat healthy and IUGR placentas using immunohistochemistry and Western blotting. Both Nrf2 and Prdx6 immunoreactivities were weaker in human and rat IUGR group placentas compared to human and rat control group placentas, respectively. Nrf2 and Prdx6 were immunostained in labyrinth trophoblasts, decidua, giant, glycogen and fetal vessel endothelial cells in rat control and IUGR group placentas. Nrf2 and Prdx6 immunoreactivities were seen in the decidua, syncytiotrophoblasts, villous stromal cells, and vascular endothelium in human control, IUGR and PE group placentas. Results of Nrf2 and Prdx6 Western blotting applied for rat and human placentas were compatible with the results of Nrf2 and Prdx6 immunohistochemical observations with regard to rat and human placentas. Down-regulation of Nrf2 and Prdx6 proteins in human and rat IUGR group placentas may have led to the formation of OS which may have impaired proliferation and invasion of cytotrophoblasts.

NSAID-gastroenteropathy: new aspects of pathogenesis and prevention.

Nonsteroidal anti-inflammatory drugs (NSAIDs) remain among the most commonly used medications because of their effectiveness in reducing pain and inflammation. Inhibitors of gastric acid secretion can substantially reduce the damaging effects of NSAIDs in the stomach and duodenum. However, there are no proven effective preventative or curative treatments for NSAID-induced enteropathy. In recent years, substantial progress has been made in better understanding the pathogenesis of NSAID-enteropathy, and in particular the interplay of enteric bacteria, bile and the enterohepatic recirculation of the NSAIDs. Moreover, it is becoming clear that suppression of gastric acid secretion significantly worsens NSAID-enteropathy.

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.

The effects of water immersion and restraint stress on the expressions of apelin, apelin receptor (APJR) and apoptosis rate in the rat heart.

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A)+WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A+WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A+WIRS group than that of the control group. Our study showed that WIRS for 6h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.

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.

The effect of docosahexaenoic Acid on visual evoked potentials in a mouse model of Parkinson's disease: the role of cyclooxygenase-2 and nuclear factor kappa-B.

This study aimed to investigate the effect of docosahexaenoic acid (DHA) on visual evoked potentials (VEPs) in a mice model of Parkinson's disease (PD). Mice model was created by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and DHA was given by gavage. Cyclooxygenase-2 (COX-2), caspase-3 activities, nuclear factor kappa-B (NF-κB) and prostaglandin E2 (PGE2) levels were determined in substantia nigra (SN) and retina. Cyclooxygenase-2 intensities were also determined immunohistochemically. The tyrosine hydroxylase (TH) immunolabelling was significantly decreased in MPTP group compared to control. Docosahexaenoic acid decreased dopaminergic neuron death in MPTP + DHA group when compared to MPTP group. Mice treated with MPTP showed motor deficits as compared to control. Significant improvement was observed in MPTP + DHA group when compared to MPTP group. Treatment with MPTP significantly increased the activity of COX-2 and total COX in SN when compared to the control group. Docosahexaenoic acid caused a significant decrease in total COX and COX-2 activity in SN of mice given MPTP. Cyclooxygenase-2 showed strong immunostaining in MPTP group when compared to other groups in SN. Levels of PGE2 increased in MPTP group when compared to control in SN. Docosahexaenoic acid treatment in MPTP group reduced PGE2 in SN. Nuclear factor kappa-B levels were found to be decreased in SN of MPTP group. The mean latencies of P1, N1, P2, N2, P3, N3, P4, N4, and P5 VEP components were significantly prolonged in MPTP group when compared to control. In MPTP + DHA group, the mean latencies of all components except P5 returned to control values. Current data shows that DHA treatment improves prolonged VEPs latencies and locomotor activity.

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.