Ellagic acid alleviates motor, cognitive and hippocampal electrical activity deficits in the male rats with 2-vessel occlusion cerebral ischemia/reperfusion.

Objective: Cerebral ischemia/reperfusion (I/R) has been known as a major cause of inability and mortality worldwide. Ellagic acid (EA) has many pharmacological effects including antioxidant, antithrombotic and neurorestoration activities. The aim of this study was evaluation of the effects of EA on motor and cognitive behaviors, hippocampal local field potential (LFP), brain oxidative stress in male rats with cerebral 2-vessel occlusion ischemia/reperfusion (2VO I/R). Materials and Methods: Forty-eight male Wistar rats (250-300 g) were assigned into six groups. 1) The Sham: rats were treated with DMSO10%/normal saline as solvent of EA 3 times daily for 1 week; 2) I/R+Veh; I/R rats received vehicle; 3-5) EA-treated groups: I/R rats received 50, 75, or 100 mg/kg EA; and 6) Cont+EA100: intact rats received EA. The cerebral 2VO I/R was made by the bilateral common carotid arteries closing for 20 min followed by reperfusion. The behavioral tests and hippocampal LFP recording were performed after treatment with EA. The oxidative stress parameters were assayed by special ELISA kits. Results: Cerebral 2VO I/R significantly decreased motor coordination, memory and hippocampal LFP and significantly increased oxidative stress. Treatment with EA improved all I/R complications. Conclusion: The current findings showed that treatment of I/R rats with EA could reverse cognitive and motor functions, and improve the LFP and oxidative stress markers. So, effects of EA on cognitive and motor function may at least in part, be due to its antioxidative actions.

Ellagic acid attenuates post-cerebral ischemia and reperfusion behavioral deficits by decreasing brain tissue inflammation in rats.

OBJECTIVES: Cerebral ischemia/reperfusion (I/R) causes brain inflammation that ultimately causes long time brain function disturbances. We aimed to evaluate the effect of ellagic acid (EA) on anxiety, depression, locomotion behaviors, blood-brain barrier (BBB) permeability, brain edema, and inflammation in male rats with cerebral I/R. MATERIALS AND METHODS: Sixty male Wistar rats (250-300 g) divided into 6 groups randomly with 10 in each: 1) Sham+Veh; rats submitted to the surgery without any I/R and received vehicle (10% DMSO in normal saline 5 ml/kg, gavages). 2) I/R+Veh; 3-5) I/R+EA; I/R rats received 50, 75 and 100 EA mg/kg, by gavages 3 times daily for one week. The cerebral I/R injury was induced by clamping the bilateral common carotid arteries for 20 minutes followed by reperfusion. Behaviors were tested one week after treatment, and brain tissue cytokines were measured by special ELISA kits. RESULTS: Cerebral I/R disrupted BBB function (P<0.001), increased brain water content (P<0.01), anxiety-like (P<0.001), depression-like (P<0.001) behaviors and cytokines in the brain tissue (P<0.001), while decreased locomotion and exploratory behaviors significantly (P<0.01 and P<0.001, respectively). Administration of EA (100 mg/kg but not other doses) could improve post-ischemic complications such as clinical signs (P<0.01), BBB function (P<0.001), brain edema (P<0.01), brain tissue cytokines (P<0.001), locomotion and exploratory behaviors significantly (P<0.05 and P<0.001, respectively). CONCLUSION: The results suggest that EA could be a potential therapeutic agent against cerebral I/R, possibly through its intertwined anti-inflammatory effects. Further research is required to investigate the involved mechanisms in details.

Exposure to ambient dusty particulate matter impairs spatial memory and hippocampal LTP by increasing brain inflammation and oxidative stress in rats.

OBJECTIVES: Exposure of healthy subjects to ambient airborne dusty particulate matter (PM) causes brain dysfunction. This study aimed to investigate the effect of sub-chronic inhalation of ambient PM in a designed special chamber to create factual dust storm (DS) conditions on spatial cognition, hippocampal long-term potentiation (LTP), inflammatory cytokines, and oxidative stress in the brain tissue. METHODS: Adult male Wistar rats (250-300 g) were randomly divided into four groups: Sham (clean air, the concentration of dusty PM was <150 µg/m3), DS1 (200-500 µg/m3), DS2 (500-2000 µg/m3) and DS3 (2000-8000 µg/m3). Experimental rats were exposed to clean air or different sizes and concentrations of dust PM storm for four consecutive weeks (exposure was during 1-4, 8-11, 15-16 and 20-23 days, 30 min, twice daily) in a real-ambient dust exposure chamber. Subsequently, cognitive performance, hippocampal LTP, blood-brain barrier (BBB) permeability and brain edema of the animals evaluated. As well as, inflammatory cytokines and oxidative stress indexes in the brain tissue measured using ELISA assays. RESULTS: Exposing to dust PM impaired spatial memory (p < 0.001), hippocampal LTP (p < 0.001). These disturbances were in line with the severe damage to respiratory system followed by disruption of BBB integrity (p < 0.001), increased brain edema (p < 0.001), inflammatory cytokines (p < 0.001) excretion and oxidative stress (p < 0.001) in brain tissue. CONCLUSIONS: Our study showed that exposure to ambient dust PM increased brain edema and BBB permeability, induced memory impairment and hippocampal LTP deficiency by increasing the inflammatory responses and oxidative stress in the brain of the rats.

A new method to induce nonalcoholic steatohepatitis (NASH) in mice.

BACKGROUND: General overnutrition is one of the key factors involved in the development of nonalcoholic fatty liver disease (NAFLD) as the most common liver disease occur by two steps of liver injury ranges from steatosis to nonalcoholic steatohepatitis (NASH). Here the effect of fructose, fat-rich and western diet (WD) feeding was studied along with aggravative effect of cigarette smoking on liver status in mice. METHODS: Sixty-four male NMRI mice were included in this study and assigned into 4 groups that fed standard, fructose-rich, high fat-, and western-diet for 8 weeks and then each group divided in two smoker and nonsmoker subgroups according to smoke exposing in the last 4 weeks of feeding time (n = 8). Histopathological studies, serum biochemical analyses and hepatic TNF-α level were evaluated in mice to compare alone or combination effects of dietary regimen and cigarette smoking. RESULTS: Serum liver enzymes and lipid profile levels in WD fed mice were significantly higher than in other studied diets. Exposing to cigarette smoke led to more elevation of serum biochemical parameters that was also accompanied by a significant increase in hepatic damage shown as more severe fat accumulation, hepatocyte ballooning and inflammation infiltrate. Elevated TNF-α level confirmed incidence of liver injury. CONCLUSION: The finding of this study demonstrated that a combination of cigarette smoke exposure and WD (rich in fat, fructose, and cholesterol) could induce a more reliable mouse model of NASH.

Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis.

Aim: Stimulation of Fas death receptor is introduced as a major cause of non-alcoholic steatohepatitis (NASH) progression through suppression of cell viability. Therefore, the blocking of death pathways is hypothesised to be express new approaches to NASH therapy. For this purpose, current experiment applied synthetic small interference RNA (SiRNA) to trigger Fas death receptor and to show its potential therapeutic role in designed NASH model. Methods: Male mice were placed on a western diet (WD) for 8 weeks and exposed to cigarette smoke during the last 4 weeks of feeding to induce NASH model. In the next step, Fas SiRNA was injected to mice aiming to examine specific Fas gene silencing, after 8 weeks. As a control, mice received scrambled SiRNA. Reversible possibility of disease was examined by 3 weeks of recovery. Results: Analysis of data is accompanied with the significant histopathological changes (steatosis, ballooning and inflammation), increased lipid profile and hepatic enzyme activities (AST, ALT, ALP) plus TBARS as well as decreased antioxidants levels in NASH model. Upon Fas-SiRNA injection, almost all measured parameters of NASH such as overexpression of Fas receptor, caspase3, NF-kB genes and marked increase of hepatic TNF-α were significantly restored and were remained nearly unchanged following recovery liking as scrambled groups. Conclusions: The suppression of Fas receptor signalling subsequent RNAi therapy may represent an applicable strategy to decline hepatocyte damages and so NASH progression in mice.

Ellagic Acid Protects Cardiac Arrhythmias Following Global Cerebral Ischemia/Reperfusion Model.

BACKGROUND: Cerebral ischemia/reperfusion (I/R) could increase the reactive oxidative stress in the cardiomyocytes. Also, some studies report cardiac arrhythmias following oxidative stressor such as I/R. Hence, this study was aimed to investigate the effects of ellagic acid (EA) against arrhythmias in a cerebral I/R model. MATERIALS AND METHODS: Thirty-two male rats were randomly allocated into four groups: Sham (normal saline, 10 days), EA (100 mg/kg EA, 10 days), I/R (20 min ischemia followed by 30 min reperfusion, 10 days), and EA + I/R (100 mg/kg EA before I/R). In all animals, electrocardiogram (ECG) was recorded pre-ischemia and postischemia on the first and 11th days, respectively. RESULTS: The I/R group showed an abnormally prolonged QTc interval after ischemia compared to the preischemia and control groups. EA administration in the EA+I/R group significantly reduced this prolonged QTc interval (P< 0.01). In the I/R group, ischemic/reperfusion resulted in a prolonged QRS complex and an elevated ST, which EA significantly prevented (P<0.01). In addition, EA significantly prevented the dramatically shortened RR interval induced by reperfusion (P<0.01). The incidence of ventricular fibrillation significantly increased in the I/R group; then it dramatically decreased following the administration of EA (P<0.0001). CONCLUSION: EA pretreatment repaired the adverse effects of I/R on the ECG parameters, which can be attributed to its negative chronotropic effects. EA pretreatment can prevent the cerebral I/R-induced heart arrhythmias.

Neuroprotective effects of gallic acid in a rat model of traumatic brain injury: behavioral, electrophysiological, and molecular studies.

OBJECTIVES: Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. Clinically, it is essential to limit the development of cognitive impairment after TBI. In the present study, the neuroprotective effects of gallic acid (GA) on neurological score, memory, long-term potentiation (LTP) from hippocampal dentate gyrus (hDG), brain lipid peroxidation and cytokines after TBI were evaluated. MATERIALS AND METHODS: Seventy-two adult male Wistar rats divided randomly into three groups with 24 in each: Veh + Sham, Veh + TBI and GA + TBI (GA; 100 mg/kg, PO for 7 days before TBI induction). Brain injury was made by Marmarou's method. Briefly, a 200 g weight was fallen down from a 2 m height through a free-falling tube onto the head of anesthetized animal. RESULTS: Veterinary coma scores (VCS), memory and recorded hDG -LTP significantly reduced in Veh + TBI group at 1 and 24 hr after TBI when compared to Veh + Sham (P<0.001), respectively, while brain tissue content of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) were increased significantly (P<0.001). Pretreatment of TBI rats with GA improved clinical signs, memory and hDG-LTP significantly (P<0.001) compared to Veh + TBI group, while brain tissue content of IL-1ß, IL-6, TNF-α and MDA were decreased significantly (P<0.001). CONCLUSION: Our results propose that GA has neuroprotective effect on memory and LTP impairment due to TBI through decrement of brain lipid peroxidation and cerebral pro-inflammatory cytokines.

Effects of ellagic acid pretreatment on renal functions disturbances induced by global cerebral ischemic-reperfusion in rat.

OBJECTIVES: Global cerebral ischemia-reperfusion (GCIR) causes disturbances in brain functions as well as other organs such as kidney. Our aim was to evaluate the protective effects of ellagic acid (EA) on certain renal disfunction after GCIR. MATERIALS AND METHODS: Adult male Wistar rats (n=32, 250-300 g) were used. GCIR was induced by bilateral vertebral and common carotid arteries occlusion (4-VO). Animal groups were: 1) received DMSO/saline (10%) as solvent of EA, 2) solvent + GCIR, 3) EA + GCIR, and 4) EA. Under anesthesia with ketamine/xylazine, GCIR was induced (20 and 30 min respectively) in related groups. EA (100 mg/kg, dissolved in DMSO/saline (10%) or solvent was administered (1.5 ml/kg) orally for 10 consecutive days to the related groups. EEG was recorded from NTS in GCIR treated groups. RESULTS: Our data showed that: a) EEG in GCIR treated groups was flattened. b) GCIR reduced GFR (P<0.01) and pretreatment with EA attenuated this reduction. c) BUN was increased by GCIR (P<0.001) and pretreatment with EA improved the BUN to normal level. d) Serum creatinine concentration was elevated by GCIR but not significantly, however, in EA+GCIR group serum creatinine was reduced (P<0.05). e) GCIR induced proteinuria (P<0.05) but, EA was unable to reduced proteinuria. CONCLUSION: Results indicate that GCIR impairs certain renal functions and EA as an antioxidant can improve these functions. Our results suggest the possible usefulness of ellagic acid in patients with brain stroke.

Preventive Effects of Ellagic Acid on Nucleus Tractus Solitarius Electrical Activity and Oxidative Stress Altered by Cerebral Global Ischemia/Reperfusion in Rat

ABSTRACT Cerebral ischemia commonly occurs when the blood flow to the entire brain or some part of the brain is disrupted. Global cerebral ischemia attenuates the nucleus tractus solitaries (NTS) EEG rhythm, increases the free radicals production and brain inflammation. Ellagic acid (EA) has antioxidative and anti-inflammatory effects against neural damages. The aim of this study was to evaluate the role of ellagic acid on EEG power in the global cerebral ischemia.Rats were divided into four groups: SO (sham) received normal saline, EA+SO, I/R (normal saline + ischemia/reperfusion), and EA + I/R. EA (100 mg/kg, dissolved in normal saline) or normal saline was administered orally (gavage) for 10 days. Animal underwent to 20 minutes of ischemia followed by 30 minutes of reperfusion in I/R and I/R+EA groups. EEG was recorded from NTS and serum antioxidant enzyme activity was measured.Data showed that ellagic acid improved electrical power of NTS. Theta and delta bands frequencies in the ischemic animals were decreased in I/R group with compared to SO group significantly (P<0.001). Ellagic acid has beneficial effect on superoxide dismutase activity in the ischemic animals with compared to I/R group (P<0.01). In contrast, ellagic acid has no significant role on glutathione peroxidase activity in the pretreated ischemic rats in comparison with I/R group.These findings suggest that ellagic acid increased antioxidant enzymes activity that scavenge the ROS due to ischemia so that it may have neuroprotective effect on NTS neurons and consequently reverse its electrophysiology pattern.

Mucosal acidification increases hydrogen sulfide release through up-regulating gene and protein expressions of cystathionine gamma-lyase in the rat gastric mucosa.

OBJECTIVES: This study was performed to investigate the effects of mucosal acidification on mRNA expression and protein synthesis of cystathionine gamma lyase (CSE), cystathionine beta synthase (CBS), and mucosal release of H2S in gastric mucosa in rats. MATERIALS AND METHODS: Thirty-two rats were randomly assigned into 4 groups (8 in each), including: the control group, HCl (10 mM) treated group, HCl (100 mM) treated group, and one group to study the effect of Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Anesthetized rats underwent tracheostomy and midline laparotomy. Ninety min after the instillation of neutral or acidic solutions, animals were sacrificed and the gastric mucosa was collected to measure the H2S concentration by ELISA method and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR (qRT-PCR). Protein synthesis was also detected by Western blot method. RESULTS: Mucosal acidification with 10 and 100 HCl, significantly increased mucosal levels of H2S (P<0.01 and P<0.001) and mRNA (P<0.01 and P<0.001) and protein expressions of CSE (P<0.01 and P<0.001). L-NAME treatment reversed H2S release to control level. CONCLUSION: Our findings indicated that mucosal acidification with HCl increased mucosal release of H2S through upregulation of CSE gene and its protein expression. This effect is mainly mediated through the involvement of nitric oxide.

Gallic acid and exercise training improve motor function, nerve conduction velocity but not pain sense reflex after experimental sciatic nerve crush in male rats.

OBJECTIVE: The aim of present study was to evaluate the effects of oral administration of gallic acid (GA) for 21 days alone and in combination with exercise on nerve conduction velocity and sensory and motor functions in rats with sciatic nerve crush. MATERIALS AND METHODS: Seventy adult male Wistar rats (250-300 g) were divided randomly into 7 groups with 10 in each: 1) Control (Cont), 2) Crushed + Vehicle (Cr +Veh), 3-5) Crushed + gallic acid (Cr+GA) (50, 100, and 200 mg/kg/2 mL, orally), 6) Crushed + exercise (Cr+Exe), and 7) Crushed + exercise + effective dose of gallic acid (Cr+Exe +GA200) for 21 days. In order to establish an animal model of sciatic nerve crush, equivalent to 7 kg of force pressed on 2-3 mm of sciatic nerve for 30 s, three times with 30 s intervals. Pain sense reflex in hot plate, motor coordination in rotarod, and sciatic nerve conduction velocity (SNCV) in all groups were tested. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p<0.05 has assigned as the significant difference. RESULTS: Pain threshold was increased significantly in untreated crushed rats while motor function and SNCV were decreased in all groups with nerve crush (p<0.05, p<0.01, p<0.001 vs. control). Pain reflex latency was not changed in treated groups. Motor coordination and SNCV were improved in groups Cr+GA200 and Cr+Exe + GA200 (p<0.05, p<0.01 vs. Cr+Veh). CONCLUSION: GA, dose-dependently, may have therapeutic potential to improve the peripheral nerve degeneration, which is most likely related, at least in part, to its antioxidant and therapeutic properties.

Gastric acid induces mucosal H2S release in rats by upregulating mRNA and protein expression of cystathionine gamma lyase.

It is well known that hydrogen sulfide (H2S) protects the gastric mucosa against gastric acid and other noxious stimulants by several mechanisms but until now the effect of gastric acid on H2S production has not been evaluated. This study was performed to determine the effect of basal and stimulated gastric acid secretion on mRNA and protein expression of cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), and on mucosal release of H2S in rats. Seventy-two male rats were randomly assigned into 9 groups (8 in each)-control, distention, and pentagastrin-induced gastric acid secretion groups. The effects of 15% alcohol solution, propargylglycine (PAG), L-NAME, and pantoprazole were also investigated. Under anesthesia, animals underwent tracheostomy and midline laparotomy. A catheter was inserted into the stomach through the duodenum for gastric washout. At the end of the experiments, the animals were killed and the gastric mucosa was collected to measure H2S concentration and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR, and expression of their proteins by western blot. Basal and stimulated gastric acid secretion increased mucosal levels of H2S, and mRNA and protein expression of CSE. Pantoprazole and L-NAME reversed H2S release and restored protein expression of CSE to the control level. Pantoprazole, but not propargylglycine, pretreatment inhibited the elevated level of protein expression of eNOS in response to distention-induced gastric acid secretion. Our findings indicated that NO mediated the stimulatory effect of gastric acid on H2S release and protein expression of CSE.

Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1ß, IL-6, and TNF-α. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1ß, IL-6, and TNF-α were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats.

The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg(-1), intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg(-1) decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3.

Bronchodilatory effect of hydrogen sulfide in rat.

OBJECTIVE(S): The aims of present study were to elucidate the effect of NaHS as a H2S donor on precontracted rat trachea smooth muscle, role of epithelium and nitric oxide in this action. MATERIALS AND METHODS: Tracheal rings from male adult Wistar rats were isolated and mounted in an organ bath containing Krebs-Henseleit solution under 1.5 g resting tension and contractions were recorded isometrically. After equilibrium period (60 min), cumulative concentrations of NaHS (0.2-1.2 mM) were applied on the tracheal basal tone or on the plateau of contractions induced by KCl (60 mM) or carbachol (CCh, 0.55 µM) in the absence and presence of certain antagonists and inhibitors. RESULTS: The tracheal basal tone was unaffected by NaHS but tracheal contractions induced by KCl and CCh were attenuated by NaHS in a concentration-dependent manner (P< 0.001). Removing the tracheal epithelial did not attenuate the NaHS spasmolytic effect in the tissue precontracted by KCl and CCh. The bronchodilatory effect was unaffected by tissue incubation (30 min, 1 µM) with, glibenclamide, propranolol, indomethacin, methylene blue (10 µM), and L-NAME (300 µM). CONCLUSION: It seems that bronchodilatory effect of H2S was not mediated by KATP channels, ß-adrenoceptors, epithelium and production of nitric oxide, cGMP and prostaglandins. Since CCh and KCl activate Ca(2+) influx and CCh promotes Ca(2+) from intracellular pool as well, therefore, we may conclude that the relaxant effect of NaHS was mediated by the Ca(2+) influx blockade and cholinergic receptors inactivation. This preliminary study shows the possible therapeutical property of H2S in obstructive pulmonary diseases.

Spasmolytic effect of stachys lavandulifolia vahl. Crude methanolic extract and fractions on rat ileum.

The aim of this study was to investigate the effect of aerial parts of Stachys lavandulifolia Vahl. Extract on the rat ileum contractions. The crude extract was prepared by maceration method (90% methanol) followed by fractionating into chloroform, ethyl acetate, petroleum ether and water. In adult male Wistar rats, ileum was sectioned and mounted in tissue bath and their contractility was recorded is otonically. KCl (60 mM)- induced ileum contractions were attenuated by crude extract and its fractions. The most potent fraction was chloroformic fraction (CF) with IC50 0.018 ± 0.126 = mg/mL. In calcium-free Tyrode solution with high K(+,) the CF (0.01 - 0.04 mg/ml) attenuated CaCl2-induced contractions (p< 0.001). The CF (0.05-0.8 mg/mL) attenuated the carbachol-induced contraction (p<0.001). The CF antispasmodic effect was reduced by naloxone (as a non-selective opioid antagonist), not by propranolol and L-NAME as ß-adrenoceptors antagonist and nitric oxide synthase inhibitor respectively. It was concluded that S . . lavandulifolia can inhibit ileum contractility mainly via disturbing the calcium mobilization and partly by opioid receptors' activation. Our results may support the traditional usage of this herb for treating diarrhea.

Gastric secretions affected by esophageal distention in the rat.

BACKGROUND: The effect of esophageal distention (ED) on gastric motility has been well documented, but only a few investigations have been carried out about the effect of ED on gastric secretions. The aim of this study was to investigate the effect of ED on gastric acid and pepsin secretions and the mechanisms involved. METHODS: Male adult Wistar rats (200-240 g) were anesthetized by urethane [1.2 g/kg, intraperitoneally (i.p.)] and underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through the duodenum for gastric washout and distention followed by the esophageal distention by a balloon (0.3 ml, 10 min). Gastric acid secretion was stimulated by gastric distension (1.5 ml/100 g body weight), pentagastrin (20 microg/kg, i.p.), or insulin (0.6 IU/kg, i.p.). Pepsin secretion was stimulated by carbachol (20 microg/kg, i.p.). Effects of cervical vagotomy and reserpine (1 mg/kg, i.p.) were also investigated. RESULTS: Gastric distention-, pentagastrin-, and insulin-stimulated gastric acid secretion was reduced by esophageal distention (P < 0.001, P < 0.05, and P < 0.05, respectively). Carbachol-induced pepsin secretion was also attenuated by esophageal distention (P < 0.05). Cervical vagotomy abolished the inhibitory effect of ED on pentagastrin-induced gastric acid secretion. In reserpinized rats, ED reduced the basal gastric acid secretion (P < 0.05). CONCLUSIONS: These results indicate that the vagus nerves are involved in the inhibitory effect of esophageal distension on gastric secretory function.

Effect of chronic restraint stress on carbohydrate metabolism in rat.

There is some evidence suggesting that stress may induce diabetes mellitus; the effects of restraint stress however need to be investigated. The present study investigates the role of chronic restraint stress on carbohydrate metabolism in male rats. The animals of the stressed group (n=8) were exposed to different restraint stressors (1 h twice daily) for 30 days. On days 1, 15 and 30, before stress exposure, the animals were weighed and fasting blood samples were obtained by tail snipping and subsequently oral glucose tolerance tests (OGTT) were carried out. Fasting plasma glucose levels on the 15th day and the plasma glucose concentrations, on the 15th and 30th days of the experiment at 15 and 60 min following OGTT, in the stressed group, were significantly higher as compared to the control group. In the stressed group, fasting plasma insulin levels on the 15th and 30th days of the experiment and the plasma insulin concentrations, on the 15th day at 15 and 60 min after performing OGTT, were significantly lower as compared to the control group. Fasting plasma corticosterone concentrations were significantly increased on the 15th day of the experiment in the stressed rats as compared to the control rats and to concentrations on the 1st day. The weights of the stressed rats on the 15th and 30th experimental days were significantly lower than the controls. In conclusion, chronic restraint stress for 30 days leads to low body weight gain in rats and impairs glucose metabolism perhaps by affecting corticosterone and insulin secretion and by inducing a degree of insulin resistance.