Healing of gastric mucosal erosions induced by indomethacin and restoration of glucocorticoids levels in the blood of rats

The study was made of the effects of low production of glucoorticoids and subsequent replacement with these hormones on healing of hemorrhagic erosions of rat gastric mucosa emerging 4 hours after administration of indomethacin (25 mg/kg percutaneously). Corticosteroid deficiency was produced by adrenalectomy or blocking function of the hypothalamo-hypophyseo-adrenocortical system by introduction of supraphysiological dose of hydrocortisone i week before indomethacin administration. Replacement therapy was conducted 4 hours after indomethacine administration by subcutaneous injection of corticosterone in a dose of 4 mg/kg. Healing was evaluated by changes in the area of damaged surface of gastric mucosa for 2 days after indomethacin administration. Plasma levels of corticosteroids were controlled. It was found that animals with corticosteroid deficiency had a larger area of mucosal lesion and slow healing vs control rats. Administration of corticosterone in physiological dose to animals with deficient production of corticosteroids stimulated healing of gastric mucosa erosions.     

The effects of desensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach in rats depend on the blood glucocorticoid hormone level

The effects of densensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach were studied before and after administration of indomethacin at an ulcerogenic dose in adrenalectomized rats receiving and not receiving replacement therapy with corticosterone and in sham-operated animals. Measures of the microcirculation consisted of blood flow rates in microvessels in the submucous layer of the stomach and the diameter and permeability of microvessels in the mucosa. Desensitization of capsaicin-sensitive afferent neurons was performed by administration of capsaicin at a dose of 100 mg/kg for two weeks and adrenalectomy one week before the experiment. Blood flow rates in microvessels and microvessel diameters were assessed in non-anesthetized rats by direct video recording methods using a special optical system with a contact dark-field epiobjective. Administration of indomethacin at an ulcerogenic dose led to decreases in blood flow rate in microvessels in the submucous layer, dilation of superficial microvessels in the mucosa of the stomach, and an increase in their permeability. Desensitization of capsaicin-sensitive neurons potentiated indomethacin-induced impairments to the microcirculation in the submucous layer and the mucosa of the stomach. These effects of densensitization were significantly enhanced in conditions of glucocorticoid hormone deficiency. Thus, glucocorticoid hormones have favorable effects on the gastric microcirculation in rats with desensitization of capsaicin-sensitive afferent neurons. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 6, pp. 700–709, June, 2008.     

Hypothalamic-pituitary-adrenocortical axis: the hidden gold in gastric mucosal homeostasis

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. Received 25 July 2006; accepted without revision 21 August 2006     

Gastroprotective action of glucocorticoid hormones during NSAID treatment

In this article we present an overview of the results of our studies suggesting that endogenous glucocorticoid hormones play a role as natural defensive factors in maintaining the integrity of the gastric mucosa during treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin and aspirin at ulcerogenic doses induce a rise in corticosterone, which helps the gastric mucosa to resist the harmful actions of these ulcerogenic agents. The gastroprotective action of glucocorticoids during NSAID treatment may be mediated by multiple actions, including maintenance of glucose homeostatis, mucus production and attenuation of enhanced gastric motility and microvascular permeability. According to our findings, glucocorticoid hormones also participate in the healing processes of NSAID-induced gastric injury. It was demonstrated that there is some cooperative interaction between glucocorticoids and prostaglandins (PGs) in gastroprotection, in a way that a deficiency of one protective factor can lead to an apparently compensatory increase of the other. The gastric mucosa becomes more susceptible to injury during deficiency of both glucocorticoids and PGs.     

Development of Insulin Resistance after Prolonged Exposure to Glucocorticoid Hormones as One of the Mechanisms of Transformation of Their Gastroprotective Effect into a Proulcerogenic Action

Neuroscience and Behavioral Physiology - This work continues our studies of the mechanisms of transformation of the initial gastroprotective action of glucocorticoid hormones into a proulcerogenic...     

Gastroprotective role of glucocorticoid hormones

Gastric ulcer disease remains widespread; a stressful lifestyle and nonsteroidal antiinflammatory drugs (NSAIDs) make significant contributions to this pathological situation. The findings overviewed here support the idea that glucocorticoid hormones released in response to acute stress or NSAIDs act as gastroprotective substances and exert many of the same actions in the stomach as prostaglandins (PGs) and nitric oxide (NO) as well as capsaicin-sensitive afferent neurons. Glucocorticoids exert a gastroprotective effect by both maintaining local defensive factors (mucosal blood flow and mucus production) and inhibiting pathogenic elements (gastric motility and microvascular permeability). Furthermore, they exert gastroprotective actions in co-operation with PGs, NO, and the afferent neurons; and their compensatory action is observed when the protective mechanism provided by either of these factors is impaired. The gastroprotective action of glucocorticoids is also associated with maintenance of general body homeostasis, including blood glucose levels and systemic blood pressure. In conclusion, glucocorticoids released in response to acute stress or NSAIDs are naturally occurring protective factors that play an important role in maintenance of the gastric mucosal integrity. This led us to re-evaluate the traditional paradigm that glucocorticoid hormones produced during activation of the hypothalamic-pituitary-adrenocortical axis are ulcerogenic in the stomach.     

Role of endogenous glucocorticoids in the healing of gastric erosions and chronic gastric ulcers in rats

To investigate the role of endogenous glucocorticoids in the healing of gastric lesions, we compared the healing of indomethacin- or cold-restraint-induced gastric erosions as well as aceticacid-induced ulcers in sham-operated rats, adrenalectomized rats and adrenalectomized rats with corticosterone replacement. Adrenalectomy was performed immediately after the formation of gastric erosions (4 h after indomethacin administration or 6 h after the onset of cold-restraint stress) or chronic ulcers (in 3 days after ingestion of acetic acid into the luminal side of the stomach). All ulcerogenic stimuli caused an increase in corticosterone production. Adrenalectomy created corticosterone deficiency and delayed the healing of gastric erosions and chronic ulcers. Replacing corticosterone reversed the deleterious effect of adrenalectomy on healing of gastric damage in adrenalectomized rats. These results suggest that glucocorticoids participate in natural healing processes of injured gastric mucosa. The data obtained also indicate that participation of glucocorticoid in the healing of gastric lesions is more evident under prostaglandin deficient conditions.     

Involvement of Hypothalamo-Hypophyseal-Adrenocortical System Hormones in Gastroprotection in Rats on Sensitization and Desensitization of Capsaicin-Sensitive Afferent Neurons

Neuroscience and Behavioral Physiology - The aims of the present work were: a) to study the contribution of glucocorticoid hormones to gastroprotection induced by sensitization of...