The increase in the noradrenalin and adrenalin levels due to stress are well documented [19
]. The present study showed that exposure to water-immersion restraint stress (WIRS) for 3.5 hours was enough to increase the level of these catecholamines significantly; noradrenalin by 92% and adrenalin by 89%. These observations support the hypothesis that adrenal catecholamines play a physiological role in response to stressful situations. Hamada et al. found that rats exposed to stress developed gastric lesions associated with reduced brain noradrenalin content and increased plasma catecholamines and corticosterone levels [22
]. Similarly, we had previously shown that rats exposed to repeated restraint stress had a higher level of plasma noradrenalin and corticosterone compared to the non-stressed rats [6
During stress, the underlying mechanisms involved are the activation of the hypothalamic-pituitary-adrenal axis (HPA) and sympatho-adrenal-medullary (SAM) systems, causing the release of corticosterone together with the release of noradrenalin and adrenalin [23
]. Furthermore, the elevation in catecholamine levels may generate free radicals [24
], which may be cytotoxic and mediate tissue damage by injuring cellular membranes and releasing intracellular components. It is widely accepted that the pathogenesis of gastric mucosal lesions involves oxygen-derived free radicals.
In the present study, the noradrenalin and adrenalin levels of stressed PVE and α-TF groups were reduced significantly in comparison to the stressed control. In parallel to its ability to block noradrenalin, vitamin E also blocked formation of gastric lesions in the rats exposed to stress. Moreover, the noradrenalin and adrenalin levels in the stressed PVE- and α-TF-treated groups were not different from their respective non-stressed groups. This suggests that vitamin E plays an important role in reducing the elevated catecholamine levels induced by stress. We had previously reported that the increase in the noradrenalin level was blocked in rats given tocotrienols supplementation but not in rats receiving α-TF [6
]. These findings suggest that tocotrienols are more potent than α-TF in blocking the effects of stress. However, we found no significant difference between the stressed PVE- and α-TF-treated groups. Both treatments were able to improve the effects of stress by reducing the levels of noradrenalin and adrenalin. The differences observed could be due to the different stress models used; acute versus repeated stress. In 2007, Campese and Shaohua showed that rats fed with a vitamin-E-fortified diet manifested a significant reduction in noradrenalin secretion from the posterior hypothalamus [25
]. A vitamin-E-fortified diet mitigated the formation of reactive oxygen species in the brain, and this was associated with a reduced sympathetic nervous system activity and blood pressure in rats with phenol-induced renal injury.
Lipid peroxidation mediated by free radicals is considered a primary mechanism of cell membrane destruction [26
]. Gastric lesions caused by stress, alcohol, Helicobacter pylori
infection and non-steroidal anti-inflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species (ROS) that seems to play an important role in producing lipid peroxides [3
]. The damage in gastric mucosa due to WIRS has been attributed to impaired gastric microcirculation, which results in ischemia followed by reperfusion, a process that generates free radicals. The finding indicates that reactive oxygen species and lipid peroxidation are important in the pathogenesis of gastric mucosal injury induced by stress [10
]. This present finding is consistent with the elevation of XO activity after stress, which produces ROS. A previous study had indicated that the exposure of rats to 3.5 hours of WIRS led to an increase in the xanthine metabolism to the level comparable to that observed in ischaemia-reperfusion model of gastric injury [2
]. Xanthine oxidase activity is a major source of ROS such as superoxide anion (O2·–
) and hydrogen peroxide (H2
) in the pathogenesis of disease in various biological systems including gastrointestinal tract [29
]. The increase in ROS would then increase the gastric lipid peroxidation and subsequent gastric lesion development. This supports the hypothesis that stress-induced injury is mediated by lipid peroxidation.
In the present study, PVE and α-TF had prevented the increase in XO
XD activities significantly after WIRS. It could be that both PVE and α-TF improved the gastric mucosal blood flow that was impaired during WIRS [2
]. Improved gastric blood flow would further suppress the conversion of XD to XO. Raghuvanshi et al. showed that administration of 400
mg of vitamin E for six days along with 80
mg of aspirin produced an excellent antioxidant effect as evidenced by a reduced platelet xanthine oxidase activity [33
Vitamin E is a lipid-soluble antioxidant and a well accepted first line defence mechanism against lipid peroxidation. It functions as a chain-breaking antioxidant for lipid peroxidation in cell membranes and as a scavenger of ROS such as superoxide anion, hydrogen peroxide and singlet oxygen [34
]. Yoshikawa et al. reported a decrease in gastric mucosal vitamin E level and an increase in gastric mucosal lipid peroxidation in ischemia-reperfusion-induced gastric mucosal injury and the severity of the injury was enhanced in vitamin E-deficient rats [35
]. Naito et al. had shown that in nitric oxide-depleted rats, vitamin E played an important protective role against ischemia-reperfusion-induced gastric mucosal injury, and suggested that this gastroprotective effect of vitamin E was not only due to its antioxidant action but also its inhibitory action on neutrophil infiltration into the gastric mucosa [36
]. Al-Tuwaijri and Al-Dhohyan reported that a single oral pre-administration of α-tocopherol acetate to rats prevented ischemia-reperfusion-induced gastric mucosal injury [37
As mentioned earlier, stress can impair gastric blood flow and cause ischemic-like conditions. These conditions can lead to reperfusion-induced injury and finally development of gastric lesions. During ischemia-reperfusion, lipid peroxidation was increased due to the production of ROS; supplementations with PVE and α-TF were able to reduce this increase. It can be concluded that PVE and α-TF have gastroprotective effects against WIRS, possibly via their antioxidant properties. As shown in this study, animals exposed to WIRS for 3.5 hours developed gastric mucosal lesions, thus confirming the reproducibility of this model for the study. Supplementations of PVE and α-TF at 60
mg/kg for 28
days prior to exposure to stress reduced the gastric mucosal injury. However, no difference between these two agents was observed, showing equal effectiveness in preventing stress-induced gastric injury.
Similarly, exposure to WIRS has been shown to increase the incidence of gastric mucosal lesion and the increase was lowered by the administration of various antioxidants [1
]. A study by Ohta et al. had demonstrated that WIRS for 6 hours reduced gastric α-tocopherol concentration but pre-administration of ascorbic acid partially reversed this reduction. In the present study, the prevention of the harmful effects of stress on the gastric mucosa may be mediated by the antioxidant activity possessed by PVE and α-TF, which reduce the formation of free radicals either directly or indirectly, leading to attenuation of lesion formation.
The protective mechanism of vitamin E and its role on human health is still not well understood. The antioxidant characteristic of vitamin E, especially its effect on polyunsaturated fatty acids (PUFA) may improve cell membrane integrity. There is possibility that the gastric tissues become more resistant towards the aggressive factors like acid and pepsin.