Effect of thymoquinone on transient receptor potential melastatin (TRPM) channels in rats with liver ischemia reperfusion model in rats.

Objectives: We aimed to investigate the levels of transient receptor potential melastatin (TRPM) gene expression, and the antioxidant and histopathologic effect of thymoquinone (Tmq) in the hepatic I/R rat model. Materials and Methods: Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Sham; Group 3: Hepatic I/R (45 min/45 min); Group 4: Tmq (50 mg/kg); Group 5: Tmq+I/R (ten days before I/R at the dose of 50 mg/kg of Tmq). The hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular clamp in the ischemia groups. The liver tissues and blood samples that were taken at the end of the study were evaluated for histopathologic and biochemical analysis. Besides TRPM gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL, and apoptosis parameters statistically decreased in Tmq and Tmq+I/R groups in comparison with the I/R group in histopathological evaluation. Results: It was observed that biochemical parameters, AST, ALT, GGT, LDH, creatinine, and urea levels significantly increased in the I/R group as compared with, sham, Tmq, and Tmq+I/R groups. It was found that TRPM2,6,7,8 gene expression decreased significantly in Tmq+I/R groups as compared to the I/R group. Conclusion: We showed that thymoquinone can inhibit the entry of Ca+2 into the cell by decreasing TRPM2,6,7,8 gene expression. Based on our findings, we think that Tmq application in the treatment of liver diseases due to I/R damage may be important in terms of both ischemia and apoptosis and can also be used in the treatment of liver-related diseases.

Behavioral and Cognitive Consequences of Obesity in Parents and Offspring in Female and Male Rats: Implications of Neuroinflammation and Neuromodulation.

Obesity is a rapidly growing public health concern that can create a family-wise burden. This study was aimed to investigate behavioral, cognitive, neuroinflammatory, and neuromodulatory consequences of the diet and parental obesity. Female and male Wistar albino rats were fed on either an obesogenic or standard diet for 12 weeks, beginning with weaning. Thereafter, the animals were matched and allowed to mate. Pups born to obese or normal parents received either the diet or standard chow to the same age. The obesogenic diet and/or parental obesity increased the locomotor activity in both females and males. The diet exhibited anxiolytic-like and antidepressant-like properties, and impaired short-term object memory as well as spatial memory. Interestingly, the obesogenic diet resulted in neuroinflammation only in naïve animals, but not in the ones with parental obesity. BDNF, SIRT1, and p53 expressions were decreased, whereas RelN expression was increased in the brain with the diet, regardless of parental obesity. Multi-factor analyses demonstrated that the obesogenic diet is the prominent influencer of cognitive, neuroinflammatory, and neuromodulatory results while parental obesity has an effect on spatial memory, neuroinflammation, and hippocampal RelN and p53 expressions. Here, we provided supporting evidence for detrimental cognitive and neuroinflammatory consequences of early life consumption of the obesogenic diet which accompanies alterations in neuromodulatory factors. Surprisingly, the diet was found beneficial against anxiety-like and depression-like behaviors, and additionally, parental obesity was demonstrated to impair some aspects of cognitive performance which appears unrelated to neuroinflammation.

CREB1 and PPAR-α/γ Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection.

Background: Hepatic ischemia/reperfusion injury is a major problem that can exacerbate complications, particularly in liver transplantations. Objectives: This study aimed to investigate the cellular mechanisms of ischemia/reperfusion injury and hepatoprotection by curcumin. Methods: Wistar albino rats were divided into four groups as Control, Sham, I/R, and Cur+I/R. Hepatic ischemia/reperfusion was induced in I/R and Cur+I/R animals, the latter of which was also given 50 mg/kg/day of curcumin for 14 days. Liver aminotransferases and the transcription regulators of inflammation (RelA, IκB, PPAR-α, PPAR-γ, CREB1) were examined along with the histological examination. Results: Hepatic ischemia/reperfusion was found to disrupt hepatic microstructure and downregulate PPAR-α, PPAR-γ, and CREB1 transcripts. Curcumin supplementation in hepatic ischemia/reperfusion recovered the structural organization and promoted the hepatocyte regeneration while increasing expressions of PPARs and CREB1. RelA and IκB were found unaltered, possibly due to the crosstalk between targeted transcripts by ischemia/reperfusion and curcumin. Conclusions: In sum, PPAR-α/γ and CREB1 were involved in hepatic ischemia/reperfusion and, moreover, were detected to be stimulated by curcumin. PPAR and CREB pathways were found to provide a route to hepatoprotection for curcumin supplementation as evidenced by the microstructural improvement.

Anticonvulsive and behavior modulating effects of sophoretin and rutoside.

INTRODUCTION: Seizures are the hallmarks of most types of epilepsies. Behavioral and cognitive impairments coincide with interictal periods even though it is not clear whether these impairments spring out of the seizure itself or accompanying sociopsychological burden of the disease. MATERIALS AND METHODS: In this study, we investigated behavioral and cognitive consequences of a single GABA receptor-related seizure in mice, and examined the potential anticonvulsive and behavior-modulating properties of sophoretin (quercetin) and rutoside (rutin). RESULTS: The study demonstrated that sophoretin and rutoside, common flavonoids of the human diet, delay the seizure onset and reduce the seizure stage. Moreover, they exerted an antidepressant-like effect, which was independent of the seizure. Neither treatments nor seizure altered recognition and spatial memory performances of the mice. CONCLUSIONS: Behavioral or cognitive disturbances that are evident in epileptic patients did not appear following a single seizure. In addition, we suggest that both sophoretin and rutoside successfully alleviate the seizure severity without interfering in the behavioral stability and cognitive performance. Hence, these flavonoids may be of use as adjuncts to the current treatment options.

Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome in a Rat Model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. METHODS: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. RESULTS: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). CONCLUSION: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.

Detrimental effects of chia (Salvia hispanica L.) seeds on learning and memory in aluminum chloride­induced experimental Alzheimer's disease.

Polyphenols and omega­3 fatty acids are thought to have beneficial effects in Alzheimer's disease, the most common cause of dementia. Seeds of chia (Salvia hispanica L.) are highly rich in these nutrients, and thus, the present study investigated the effects of chia seeds on behavior and cognition in an aluminum­induced Alzheimer's disease model in rats. Experimental animals received chia supplementation either during the generation of the model (i.e., pretreatment) or after the model was established (i.e., treatment). A battery of behavioral and cognitive tests were performed, including open­field, elevated plus maze, Porsolt's forced swim, and Morris' water maze, to evaluate anxiety­ and depression­like behaviors, and learning and memory. Results showed that chia supplementation was ineffective against Alzheimer's­related anxiety, whereas depression­like behaviors were attenuated with both pretreatment and treatment. There was no improvement in learning and memory with chia treatment. Rather, cognitive performance in chia­pretreated animals was remarkably worse as compared to their non­treated disease­induced counterparts. Hippocampal concentrations of amyloid-ß42, amyloid precursor protein, and total tau protein were similarly increased in all disease­induced animals (despite chia supplementation), as compared to the controls. Based on these findings, chia supplementation during the progression of Alzheimer's disease may exacerbate the disease. Although the results presented here emerge from an experimental/preclinical study, we suggest cautious and careful use of chia, especially in early­stage Alzheimer's patients, until future research in different experimental settings is conducted.

Lecture attendance improves success in medical physiology.

The educators have underlined the importance of lecture attendance for decades. Nowadays, students have ample online educational sources, which began a debate on the necessity of in-class lectures. In the present study, we investigated the influence of lecture attendance on the exam success. To this aim, we adopted a novel approach and matched second-year medicine students' answers in three interim exams with the lectures related to those questions. Thereby, we were able to evaluate if attending lectures increases the chance of giving a correct answer to the exam question generated from the attended lecture. Furthermore, we examined students who had never taken the course before (first-time takers) and students who had failed and repeated the course (repeat takers) separately, since repeat takers may have attended a lecture previously. We found that first-time takers attended more lectures and gained higher total scores than repeat takers. Lecture-matched correct answers were significantly higher for attended lectures than for skipped lectures in all interim exams. Moreover, the correlation analyses revealed that the number of correct answers increases by lecture attendance in both first-time and repeat takers. These results indicate that in-class lectures still should be considered as an essential part of the medical physiology education, even in the internet era.

Systemic side effects of locally used oxymetazoline.

OBJECTIVES: The object of the study is to experimentally investigate the possible systemic side effects of Oxymetazoline including its nasal spray which has been in use for a long time both by the physicians and patients. There is no study in the literature to address the damages of oxymetazoline on the end organ. MATERIALS AND METHODS: The study conducted on 2 groups of rat. Group 1 (n = 8): Control; and Group 2 (n = 8): Oxymetazoline. During 4 week, the control group was applied with 2 drops of saline water on each nasal cavity 3 times a day and the other group was applied with 2 drops of oxymetazoline HCl 3 times a day. At the end of experiment, samples from mandible, parotid and tails of the rats were taken in 10% formalin for histopathological investigations. RESULTS: In histopathological experiments, when compared with the control group, the oxymetazoline group showed significant increase in many of the histopathological parameters (ischemic changes: P = 0.0001; congestion: P = 0.0006; arterial thrombosis: P = Ns; PNL accumulations: P = 0.001; necrosis: P = 0.0001; and ulceration: P = 0.014). The results of histopathologic tests on the samples taken from mandible and parotid gland, in comparison with the control group, showed no significant increase (focal inflammation: P = Ns; and lymphocyte aggregation: P = Ns). CONCLUSION: Due to the damage that the long-term use of nasal spray including oxymetazoline, it may cause injury on the end organ, which we revealed in our histopathological experiments. We believe that it's essential for the physicians to provide information on the side effects of the medicine to their patients who use for a long term.

The association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide concentration with microalbuminuria in patients with gestational diabetes.

AIM: Gestational diabetes mellitus (GDM) is a glucose intolerant condition that affects 14% of all pregnancies. Diabetes mellitus (DM) occurs in 30 - 70% of patients with GDM after delivery. DM and GDM are associated with structural and functional deterioration of the renovascular system. Our aim is to investigate the association Glu- 298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene with serum nitric oxide levels and microalbuminuria in patients with GDM and healthy pregnancies. MATERIAL AND METHODS: Serum nitric oxide (NO) levels, urinary excretion of albumin and Glu298Asp polymorphism of the eNOS gene were analyzed in 68 patients with GDM and 73 healthy controls. High performance liquid chromatography (HPLC-Griess) method was used to analyze serum NO levels. Microalbuminuria was evaluated by rate nephelometry method. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: Nitric oxide, glucose, creatinine, and microalbuminuria were significantly different between the patients and the control subjects (p = 0.001, p = 0.001, p = 0.002, and p = 0.005, respectively). There was a significant difference between groups in terms of the ratio of GG/GT+TT of eNOS gene Glu- 298Asp (p = 0.02). The patients with GT+TT genotype had significantly higher microalbuminuria levels and lower NO concentrations (22.16 vs. 9.51, p = 0.005, and 10.56 vs. 12.73, p = 0.021, respectively). The presence of T allele of eNOS gene is an independent predictor of microalbuminuria (OR: 2.346, 95% confidence interval: 1.247 - 5.238, p = 0.02) as well as serum glucose and NO concentration. CONCLUSION: The G894T polymorphism of eNOS gene and decreased NO concentration seem to be independent predictors of increased urinary excretion of albumin in patients with GDM. Determining the frequency of eNOS gene G894T polymorphism may help to identify pregnancies at increased risk of microalbuminuria.

Association with leptin gene C.-2548 G>A polymorphism, serum leptin levels, and body mass index in Turkish obese patients.

Leptin is a protein hormone which plays a critical role in the regulation of both body-weight through reducing food intake and stimulating energy expenditure. Several polymorphisms in leptin gene (LEP), which encodes for leptin, have been described. However, its association with obesity is still controversial. Therefore, in the present study, we aimed to investigate whether LEP c.-2548 G>A polymorphism was associated with serum leptin levels, lipid parameters, and body mass index in Turkish obese patients. Forty-seven obese patients and 48 healthy individuals were included in the study. Blood samples were collected for DNA extraction. LEP c.-2548 G>A polymorphism were detected using polymerase chain reaction-restriction fragment length polymorphism technique. Serum leptin levels and lipid parameters were measured by ELISA and enzyme colorimetric assay techniques, respectively. GA or AA genotypes and A allele carrier frequencies of the c.-2548 G>A polymorphism in the LEP were higher in obese (38.3, 34.0 and 72.3 %) when compared with controls (14.6, 12.5, and 27.1 %; p = 0.011, 0.016, and 0.002, respectively). On the other hand, AA or AG genotypes were also related to increased serum leptin levels (p < 0.001) and body mass index (p < 0.0001). All these consequences showed that LEP -2548 AA or AG genotypes are important predictors for increased levels of leptin and BMI in Turkish obese patients and it may be a useful marker for obesity risk in our population.

Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model.

It has been suggested that free oxygen radicals play a role in the genesis of epilepsy and in post-seizure neuronal death. The aim of this study was to investigate the dose dependent effect of ghrelin on pentylenetetrazole (PTZ)-induced oxidative stress in a rat seizure model. For this purpose, the ghrelin groups were treated with intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80 microg/kg before the PTZ injection. Superoxide dismutase (SOD) and catalase (CAT) activities, and reduced glutathione (GSH) and thiobarbituric acid-reactive substance (TBARS) levels were measured in erythrocytes, liver and brain tissue. TBARS, the indicator of lipid peroxidation, was significantly increased in erythrocytes, liver and brain tissue, while antioxidant enzyme activities and glutathione levels were significantly decreased in PTZ injected rats. Ghrelin pretreatment prevented lipid peroxidation and the reduction in antioxidant enzyme activities and GSH levels against PTZ-induced oxidative stress in a dose dependent manner. The present data indicates that PTZ at a convulsive dose induces an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in the erythrocytes, liver and brain of rats. Ghrelin pretreatment diminished oxidative stress and prevented the decrease in antioxidant enzyme activities, and thus may reduce neuronal death in the brain during seizures. However, further studies are needed in order to confirm our hypothesis.

Effect of mesalamine on healing in experimental colon anastomosis: a randomised experimental study.

OBJECTIVE: We aimed to investigate the effect of mesalamine on healing of experimental colon anastomosis model. MATERIAL/METHODS: Forty adult male Wistar albino rats were performed segmentary colonic resection and end-to-end anastomosis. Animals were randomly divided into four groups: group I, anastomosis group, received no treatment (GI, n=8); group II, anastomosis+oral mesalamine group (100mg/kg/day); group III, anastomosis+rectal mesalamine (2mL) group, (GIII, n=8); group IV, anastomosis+oral mesalamine+rectal mesalamine (GIV, n=8) group. A sham group (n=8) was constituted and was performed laparotomy. Bursting pressure, hydroxyproline levels and histopathological characteristics of the anastomosis were analyzed. RESULTS: Although it was not statistically significant, there was an increase in the burst pressure of the mesalamine group. When hydroxyproline measurements were compared there were statistically significant difference between the non-treated colon and all groups. There were significant differences between GI and GIII-GIV, GII and GIV. The differences between group I and II and group II and III were not statistically significant. When we compared the median amount of the histopathological changes, we found significant difference between the anastomosis and the mesalamine groups (P<0.05). But when mesalamine groups were compared with each other we did not observe a significant difference. CONCLUSION: Mesalamine had positive effects which were not statistically significant on bursting pressure and statistically different significant effects on hydroxyproline (HP) levels based on the way of administration and statistically significant positive effects on histopathologic anastomotic healing in experimental anastomosis model.

Serum nitric oxide levels and flow-mediated dilatation in patients with Sheehan syndrome and the effect of combination therapy consisting of L-thyroxine, prednisolone, and conjugated estrogen/medroxyprogesterone acetate.

Baseline and stimulated nitric oxide (NO) levels were higher, whereas baseline arterial diameter, FMD-stimulated NO increment, and arterial dilatation ratio were lower in Sheehan syndrome (SS) patients than in control subjects. After combination therapy consisting of prednisolone, L-thyroxine, and conjugated estrogen, baseline and stimulated NO levels of SS remained as high, but FMD-stimulated NO, NO increment ratio, and arterial dilatation ratio increased with treatment.

Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats.

Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropine+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 microg/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P<0.01, P<0.05, P<0.05, P<0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats.

Alteration of nitric oxide production in rats exposed to a prolonged, extremely low-frequency magnetic field.

The purpose of this study is to investigate the possible effect of an extremely low-frequency magnetic field (ELF-MF) on nitric oxide (NO) level. In this study, 27 male Sprague-Dawley rats were used. The rats were divided into three groups: two experimental and one control (sham-exposed). The first and second experimental group (n = 10) were exposed to 100 microT and 500 microT ELF-MF during 10 months, 2 h a day, respectively, and the third (n = 7) group was treated like an experimental group except for ELF-MF exposure in methacrylate boxes. After ELF-MF and sham exposure, serum nitrite levels were measured by Griess reaction. A significant reduction was observed in nitrite levels among the first and second experimental groups of rats and sham-exposed rats after exposure for 10 months, 2 h a day, to ELF-MF of 100 and 500 microT (p < 0.01). These results suggest that prolonged ELF-MF exposure at intensities of exposure limits, determined by ICNIRP for public and occupational, may reduce NO production probably affected by NO generation pathways.

Antiepileptic effects of ghrelin on pentylenetetrazole-induced seizures in rats.

It is well known that neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA) exert antiepileptic effects in animal models. It has recently been shown that ghrelin neurons increase the activities of GABA and NPY in the brain. Therefore it can be said that ghrelin is an antiepileptic agent. In this study we aimed to investigate the antiepileptic effect of ghrelin in an acute experimental epilepsy model in pentylenetetrazole (PTZ) injected rats. Adult male Wistar albino rats were divided into a control group and four experimental groups with seven rats in each group. In order to generate epileptic seizures, PTZ (50mg/kg) was injected intraperitoneally. The experimental groups received intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80microg/kg 30min before PTZ injection. After PTZ injection, the latencies were separated into three components: first myoclonic jerk, generalized clonic seizures and tonic generalized extension. The injection of 50mg/kg PTZ-induced epileptic seizures in the control group. The onset times of the three characteristic behavioral changes were significantly delayed and the duration of tonic generalized extension was diminished by dose-dependent ghrelin administration. Our results demonstrated that ghrelin suppresses the onset time of PTZ-induced seizures. In the light of our current knowledge, it seems that ghrelin may be considered as an antiepileptic drug.

Effect of nitric oxide on phagocytic activity of lipopolysaccharide-induced macrophages: possible role of exogenous L-arginine.

Among the antimicrobial mechanisms associated with macrophages, NO produced by iNOS plays a major role in intracellular killing, but the relationship between NO and phagocytic activity after injection of inflammatory agents into the peritoneal cavity is not clear. The aim of the present study was to investigate the effect of nitric oxide (NO) on macrophage function after treatment with intraperitoneal lipopolysaccharide (LPS) and the role of exogenous L-arginine administration in this event. Six experimental groups and one control group, each consisting of seven Wistar rats were used: Group I: Control; Group II: LPS; Group III: LPS+L-arginine; Group IV: LPS+L-arginine+Aminoguanidine; Group V: LPS+Aminoguanidine; Group VI: L-arginine; Group VII: Aminoguanidine. Macrophage phagocytic activity and total plasma nitrite levels were increased in the LPS group. In the LPS+L-arginine group, both the phagocytic activity and total plasma nitrite levels showed large increases. Administration of aminoguanidine (AG), a specific iNOS inhibitor, abolished macrophage phagocytic activity and total plasma nitrite levels in the LPS and LPS+L-arginine groups. As a result, we showed that NO produced by macrophages has a role not only in intracellular killing, but also in phagocytic activity.

Change of nitric oxide concentration in men exposed to a 1.5 T constant magnetic field.

This study was carried out in order to determine nitric oxide (NO) production immediately after a 1.5 T magnetic field 30 min exposure to an experimental group, comprising 33 healthy young male volunteers aged 18-26 years old. In addition, a control group, comprising 30 healthy male volunteers aged 19-26 years old, was not exposed to the magnetic field and their NO levels were also measured. The experimental group was exposed using a magnetic resonance imaging (MRI) apparatus. Nitrite and nitrate concentrations were determined by UV-VIS spectrophotometer. The results, related to the parameters measured in this study, were analyzed by one-way ANOVA. Total nitrite concentration in post-magnetic field samples was found to be higher than in pre-magnetic field samples (P < .05).

Effect of ghrelin administration on phagocytic activity in acute cold-restraint stress exposed rats.

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, was identified in the rat stomach. This peptide acts through nitric oxide (NO) by expressing endothelial nitric oxide synthase (eNOS) and down regulating inducible nitric oxide synthase (iNOS) at its gastroproprotective effect against restraint stress induced damage. Recently the ghrelin receptor has also been detected in peripheral systems including immune tissue. We have investigated the possible effect of ghrelin on phagocytic activity of peritoneal macrophages in acute cold-restraint stress (ACRS) exposed rats. The rats were divided into control, stress and ghrelin groups. In ghrelin groups, single dose and three days consecutive dose of ghrelin (20 microg/kg. i.p.) were applied to rats that were exposed to ACRS for 4 h. 1 ml of saline was injected i.p. after ACRS for 3 consecutive days to the rats of the stress groups. Ghrelin administration reduced the increased phagocytic activity induced by ACRS. We conclude that ghrelin exerts an important role at macrophage phagocytic activity in ACRS exposed rats.