Hypothalamic-pituitary-adrenocortical axis: the hidden gold in gastric mucosal homeostasis.
ABSTRACT The results overviewed in the present article suggest that glucocorticoids released during acute activation of hypothalamic-pituitary-adrenocortical (HPA) axis are important gastroprotective factors, allowing us to re-evaluate the traditional point of view about their ulcerogenic role. It has been shown that various ulcerogenic stimuli induce an increase in glucocorticoid production that in turn helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Glucocorticoids released in response to mild stress contribute to adaptive gastric cytoprotection. The gastroprotective action of glucocorticoids is accounted for by maintaining the local defensive factors and inhibiting the pathogenic elements. Maintenance of glucose and temperature homeostasis as well as systemic blood pressure by glucocorticoid hormones could be a fundamental of their beneficial action on various gastric targets. Thus, glucocorticoids released during activation of HPA axis may contribute to the gastric mucosal homeostasis through their contribution to general body homeostasis.
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ABSTRACT: Adaptive cytoprotection is a concept to counteract against the gastric mucosal injury caused by stress, strong irritants and drugs such as non-steroidal anti-inflammatory drugs. The process is mediated through diverse mediators and mechanisms. Studies on adaptive cytoprotection began from the discovery of prostaglandin (PG)-dependent and PG-independent pathways, followed by the investigation on the types and concentrations of mild irritants to be used. Upon the confirmation on the importance of the vagus nerve and the vago-vagal pathway in regulating the mucosal protective actions of the mild irritants, individual participating mediators for the neuronal modulatory processes were explored, including peptide neurotransmitters such as calcitonin gene-related peptide and substance P. Further correlation with the sympathetic nervous system, the sensory afferent neurons and the enteric nervous system of the gastric mucosa had been made. A close working relationship between the hypothalamic-pituitary-adrenal axis, the autonomic nervous system and the enteric nervous system was then proposed, with concurrent regulation of PG, nitric oxide and sensory neuropeptides by different mild irritants. Apart from these conventional concepts, there are now contemporary ideas on newer forms of adaptive cytoprotection such as ischemic preconditioning and heat-shock proteins, which will cast new light to novel approaches in facilitating gastric mucosal protection.Digestion 01/2011; 83 Suppl 1:19-24. · 1.94 Impact Factor
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ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among some of the most commonly used medications. Serious adverse effects induced by NSAIDs may occur not only in the upper gastrointestinal tract, but in the small intestine and cardiovascular system. However, these side effects are studied and investigated separately. Here we tested the hypothesis that the healing of indomethacin-induced gastric erosion may be followed by small intestinal and cardiovascular adverse effects. First we examined the development of gastrointestinal lesions 4-24-48-72 h after a single indomethacin (35 mg/kg s.c.) injection given to fasted male rats (refeeding after 4 h). Then with a telemetric device heart rate, core body temperature and locomotion changes were recorded in the freely moving animals for 72 h after indomethacin or its vehicle injection (control). Indomethacin produced hemorrhagic erosion in the glandular stomach 4 h after its administration which was almost completely healed 48 h later. Parallel to the healing a gradual increase of injury to the small intestine became apparent. The control rats' heart rate, core body temperature and locomotion all agreed with a normal circadian rhythm. However, the circadian cycle of rats treated with indomethacin in 24 h after its administration was disrupted: their heart rate rose to it's maximal level and their locomotion and core temperature values fell to their minimal. These results suggest that the healing of gastric erosion induced by a single indomethacin injection may be followed by other pathological events outside of the stomach, among which there may be intestinal injury and a loss of a normal circadian cycle of heart rate as well as body temperature and locomotion.Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2011; 62(6):619-25. · 2.48 Impact Factor
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ABSTRACT: Stress may contribute to the development and progression of gastrointestinal disorders. Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the main characteristics of stress. For several decades it was generally accepted that glucocorticoids released during stress are ulcerogenic hormones. We designed some experimental studies in rats to clarify the validity of this widely held view. To achieve this goal, we examined the effect of glucocorticoid deficiency followed by corticosterone replacement or the glucocorticoid receptor antagonist, RU-38486, on stress-induced gastric erosion and the parameters of gastric function in rats. The data obtained shows that the reduction in the stress-induced corticosterone release, or its actions, aggravates stress-caused gastric erosion. It is suggested that an acute increase in corticosterone during stress protects the stomach against stress-induced injury. According to our results, various ulcerogenic stimuli, similar to stress, induce an increase in corticosterone that helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Glucocorticoids exhibit their gastroprotective effect by both maintaining local defensive factors and inhibiting pathogenic elements. Furthermore, the contribution of glucocorticoids to gastroprotection is tightly related to their contribution to general body homeostasis. Glucocorticoids provide gastroprotective actions in co-operation with prosta-glandins, nitric oxide and capsaicin-sensitive sensory neurons. The results obtained do not support the traditional paradigm and suggest that glucocorticoids released during acute activation of the HPA axis are naturally occurring gastroprotective factors. In this article, we review our recent publications on the role of glucocorticoids in gastroprotection.Therapeutic advances in chronic disease. 09/2011; 2(5):333-42.