Effect Of Cold-restraint Stress Research Articles

The Use of Pistacia Lentiscus Chia Resin Versus Omeprazole in Protecting Male Rats Peptic Mucosa Against Cold Restraint Stress.

IntroductionPeptic mucosal damage induced by acute stress is a serious cause of morbidity and mortality in critically ill patients. The study aimed to investigate the protective, antioxidant and anti-inflammatory effects of pretreatment with Chios mastic gum (CMG), a traditionally consumed herbal resin naturally deriving from the trunk of Pistacia Lentiscus var. Chia compared to Omeprazole, a standard medication used in the prevention and treatment of gastritis, against the effects of cold restraint stress (CRS) in rat gastric and colonic mucosa.MethodsTwenty-one male Wistar rats were randomly assigned to three groups: Control (C), Omeprazole (O), and CMG (M), according to the pre-treatment regime, and were subjected to CRS at 40C for 3 hours. The gastric and colonic mucosal lesions were histologically assessed. ELISA measured blood concentrations of TNF-α, IL-1β, peroxidase, superoxide dismutase (SOD) and total antioxidant capacity (TEAC).ResultsIn both groups, O and M, gastric mucosal hyperemia, haemorrhagic infiltration and mucosal oedema, as well as colonic mucosal hyperaemia and haemorrhagic infiltration were significantly reduced compared to the controls (p<0.05). No significant differences were observed between Groups O and M. TNF-α levels were significantly lower in group M compared to Group O (p=0.013). IL-1β levels were significantly depressed in groups M and O compared to control (p≤ 0.001). The activity of both peroxidase and SOD enzymes decreased in group M compared to group O (p= 0.043 and p=0.047 respectively) and the control (p=0.018 and p< 0.001 respectively).ConclusionsThe natural Chios mastic gum is a promising nutritional supplement with protective properties to the peptic mucosa against CRS, exerting anti-inflammatory and antioxidant effects.

C-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium

Gastrointestinal epithelium faces osmotic stress, both at physiological and pathophysiological conditions. JNK activation is an immediate cellular response to osmotic stress. We investigated the effect of osmotic stress on intestinal epithelial barrier function and delineated the role of JNK2 in osmotic stress-induced tight junction (TJ) regulation in Caco-2 cell monolayers and ileum of Jnk(-/-) and Jnk2(-/-) mice. The role of JNK activation in osmotic stress-induced TJ disruption was evaluated using JNK-specific inhibitor and antisense oligonucleotides. Furthermore, the effect of cold restraint stress in vivo on TJ integrity was determined in rats. Osmotic stress disrupted TJs and barrier function in Caco-2 cell monolayers without affecting cell viability. Osmotic stress activated JNK1 and JNK2 and the inhibition of JNK by SP600125 attenuated osmotic stress-induced TJ disruption. TJ disruption and barrier dysfunction by osmotic stress was associated with JNK-dependent remodeling of actin cytoskeleton. Knockdown of JNK2 accelerated TJ assembly and attenuated osmotic stress-induced TJ disruption in Caco-2 cell monolayers. In mouse ileum in vitro, osmotic stress increased paracellular permeability, which was attenuated by SP600125. Osmotic stress disrupted actin cytoskeleton and TJs and increased paracellular permeability in the ileum of wild-type and JNK1(-/-) mice, but not in JNK2(-/-) mouse ileum. Cold restraint stress activated JNK in rat ileum and caused JNK-dependent remodeling of actin cytoskeleton and redistribution of occludin and zona occluden-1 from the intercellular junctions. These results reveal the role of JNK2 in the mechanism of osmotic stress-induced TJ disruption in the intestinal epithelium.

The Effect of Stress and in Vivo Vasoactive Intestinal Peptide (VIP) Treatment on the Response of Isolated Rat Aorta to Norepinephrine, Angiotensin II and Vasopressin, and Adventitial Mast Cells

The effects of cold-restraint stress, repeated over 3 days, and treatment of rats with vasoactive intestinal peptide (VIP) on the contractile responses of isolated aorta to vasoconstrictors, and on aortic adventitial mast cells were investigated. Stress significantly reduced the contractile response of rat aorta smooth muscle to norepinephrine (NE), angiotensin II (Ang II) and vasopressin (VP). Decreased sensitivity to NE, Ang II and VP may result from decreased receptor density, and affinity or reduced effector efficacy. Stress induced degranulation, decreased the number and changed the granular content of mast cells; all degranulated mast cells were stained with alcian blue, and the percentage of safranin staining cells was decreased. Given prior to stress, VIP reversed the reduced contractile responses and sensitivity of aorta to NE and Ang II but had no effect on VP subsensitivity. VIP also inhibited stress-induced degranulation of mast cells, and after VIP only alcian blue-stained mast cells were seen. When VIP was given to non-stressed rats, the contractile response of the aorta to NE, but not Ang II or VP, was increased compared with control. Mast cell count was decreased in the adventitia of non-stressed VIP treated rats. The results indicate that stress decreases the heparin content of mast cells and VIP has an additive effect. In conclusion, VIP modulates both stress-induced mast cell activity and reduced sensitivity of aorta smooth muscle to NE and Ang II. It can be suggested that VIP may moderate some effects of stress on vascular pathophysiology.

Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach

The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4 degrees C for 1-3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir-SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach.

Effect of stress on the antioxidant enzymes and gastric ulceration.

The effect of cold-restraint stress on the antioxidant enzymes of the rat gastric mucosa was studied with a view to finding out their role in stress induced gastric ulceration. Histological examination revealed stress induced extensive damage of the surface epithelial cell with lesions extending up to submucosa in some cases. Stress causes time-dependent increase in histamine and pepsin content but decrease in acid content of the gastric fluid with the progress of ulceration (ulcer index) for two hours. The tissue lipid peroxidation was significantly increased as evidenced by accumulation of malondialdehyde. Since lipid peroxidation results from the generation of reactive oxygen species, stress effect was studied on some antioxidant enzymes such as superoxide dismutase, peroxidases and prostaglandin synthetase as a function of time. The time dependent increase in stress ulcer correlates well with the concomitant increase in superoxide dismutase activity and decrease in peroxidase and prostaglandin synthetase activity. This creates a favourable condition for accumulation of endogenous H2O2 and more reactive hydroxyl radical (OH.). Administration of antioxidants such as reduced glutathione or sodium benzoate prior to stress causes significant decrease in ulcer index and lipid peroxidation and protection of gastric peroxidase activity suggesting the involvement of reactive oxygen species in stress induced gastric ulceration. This is supported by the in vitro observation that OH. can also inactivate peroxidase and induce lipid peroxidation. As prostaglandin is known to offer cytoprotection, stress-induced loss of prostaglandin synthetase activity appears to aggravate the oxidative damage caused by reactive oxygen species.

Stress-induced gastric mucosal lesion and platelet aggregation in rats.

The effect of cold-restraint stress on platelet function in vitro was studied in the rat model. Platelet function was assessed by platelet aggregation in response to adenosine diphosphate (ADP) and thrombin. ADP-induced platelet aggregation was reduced in platelet-rich plasma after 2 h of cold-restraint stress. Thrombin-induced platelet aggregation was reduced with time during cold-restraint stress with a parallel increase in the lesion index. Although pretreatment of animals with atropine prevented the development of gastric mucosal lesions, platelet dysfunction was not reversed by this treatment. These results suggest that cold-restraint stress may impair platelet function, probably due to platelet activation in vivo, and that the abnormalities in platelet function may be associated with the development of gastric mucosal lesions.

The effect of cold restraint stress on plasma lithium concentration in rats

In the present study plasma lithium concentrations have been shown to be significantly higher in rats which were given lithium chloride (LiCl) and subjected to stress and given both LiO and indomethacin and subjected to stress than those which were given only LiO. Renal prostaglandins are important mediators of renal electrolyte excretion. When the previous report on the inhibitory effect of acute stress on the endogenous gastric prostaglandin synthesis was taken into consideration, our results suggest that acute stress may lead to increased plasma lithium levels by inhibiting renal PG synthesis similar to the effect of indomethacin.

Effect of cold-restraint stress on glutathione and lipid peroxide levels in the liver and glandular stomach of rats

The effect of starvation and cold-restraint stress on glutathione and lipid peroxide levels in the liver, stomach and plasma of rats was investigated. Hepatic and gastric glutathione levels were significantly decreased in starvation and cold-restraint groups when compared with values obtained from the control group. In both tissues, lipid peroxide levels were significantly decreased after starvation but were not significantly different from control values after cold-restraint treatment. However, when compared with the values obtained from the starvation group there was a significant increase in both hepatic and gastric lipid peroxide levels after cold-restraint. Plasma lipid peroxide levels were slightly decreased in the starvation group and significantly increased in the cold-restraint group. Our results suggest that pathological consequences of stress on different tissues could be due to stimulation of lipid peroxidation.

Effects of cold-restraint stress on gastric ulceration and motility in rats

The effects of stress by restraint at 4°C for 2 hr and of drug treatment on gastric lesion formation and motor activities (contraction frequency, amplitude and tone) were studied in rats. Restraint at room temperature (22°C) produced a small ulcer index in the controls and did not significantly affect gastric motor activities; atropine and verapamil reduced but bethanechol increased gastric contractions under the same experimental conditions. Restraint at 4°C markedly elevated the ulcer index. The frequency of gastric contractions was significantly increased in the first hr but the amplitude was depressed during the whole 2-hr observation period. Gastric tone initially fell but rose in the second hr of cold-restraint stress. Atropine and verapamil pretreatment prevented stress-induced ulcer formation and suppressed the frequency and amplitude of gastric contraction. Bethanechol stimulated both frequency and amplitude without significantly influencing stress ulcer size. It is unlikely that gastric hypermotility plays a major role in stress ulceration; the stomach smooth muscle-relaxing action of atropine and verapamil may contribute only partly to their antiulcer effects.

The effect of cold-restraint stress on gastric emptying in rats

The effects of drug treatment and of cold-restraint stress (a method used to produce experimental stomach ulcers) on gastric emptying of a resin (colestipol-phenol red complex) were investigated in rats. Gastric emptying was decreased by intraperitoneal treatment with atropine (0.3 mg/kg) or verapamil (4 mg/kg), and enhanced by bethanechol (1.2 mg/kg). Stress by restraint at 4°C for 2 hr markedly reduced gastric emptying; the pattern of effects of drug pretreatment in these stressed rats was similar to that seen in their nonstressed controls. Further experiments, with stress for 3 hr, revealed that the gastric emptying rate was triphasic; increasing in the first hr, returning to normal and then slowing in the third hr of stress. Initial increase in emptying rate was probably due to predominant vagal overactivity. Hypothermia and possibly other factors induced by cold-restraint stress could have subsequently depressed gastric motility.

Effects of cold-restraint stress on rat gastric and hepatic glutathione: A potential determinant of response to chemical carcinogens

Stressor-induced decreases in glutathione (GSH) concentrations were demonstrated in the liver and the gastric mucosa. Either food deprivation and/or the time of day the stressor was administered could affect the extent of stressor-induced decreases in GSH. The system described may be useful for further exploration of potential stressor-induced alterations in susceptibility to chemical carcinogens and/or other toxins whose expression of biological activity may be dependent upon GSH.