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L P Filaretova

Publications and source records attributed to L P Filaretova.

At least 19 recordsLinked to original sources
PubMed2006

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.

Animals↗
PubMed2006

[Activation of hypothalamic-pituitary-adrenocortical system as important gastroprotective component of stress reaction].

The review is focused on the action of glucocorticoids released during activation of hypothalamic-pituitary-adrenocortical axis, on the susceptibility of gastric mucosa to injury. The data support the idea that glucocorticoids produced in response to acute stress or other ulcerogenic stimuli have a gastroprotective action but not ulcerogenic one as it has generally been considered for some decades. It has been shown that gastroprotective action of glucocorticoids may be mediated by multiple actions, including maintenance of glucose homeostasis, gastric mucosal blood flow, mucus production and attenuation of enhanced gastric motility and microvascular permeability. For maintenance of gastric mucosal integrity glucocorticoids may cooperate with other gastroprotective factors. Glucocorticoid hormones exert a pivotal role in the maintenance of gastric mucosal integrity in the case of impaired gastroprotective mechanisms provided by prostaglandins, nitric oxide and capsaicin-sensitive sensory neurons. These findings indicate that activation of hypothalamic-pituitary-adrenocortical system could be considered as a significant hormonal gastroprotective component of stress reaction and therefore glucocorticoid hormones are natural gastroprotective factors.

Animals↗
PubMed2006

[Compensatory gastroprotective action of glucocorticoid hormones in the rats with ablation of capsaicin-sensitive neurons].

We tested the hypothesis that contribution of glucocorticoids in gastroprotection become especially important during ablation of capsaicin-sensitive neurons. For this, the effect of desensitization of capsaicin-sensitive neurons on the gastric mucosa was compared in groups of rats with different glucocorticoid supply: sham-operated and adrenalectomized without and with corticosterone replacement (4 mg/kg sc). Functional ablation of capsaicin-sensitive neurons was performed with neurotoxic doses of capsaicin (20 + 30 + 50 mg/kg sc). Indomethacin in the dose 35 mg/kg was given as an ulcerogenic stimulus. It was shown that combination of adrenalectomy with desensitization of capsaicin-sensitive neurons potentiated the effect of sensory desensitization alone on indomethacin-induced gastric erosions. Corticosterone replacement prevented this effect of adrenalectomy. The results suggest a pivotal compensatory role of glucocorticoids in maintenance of gastric mucosal integrity during ablation of caspsaicin-sensitive sensory neurons.

Adrenalectomy↗
PubMed2005

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). In-domethacin 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 homeostasis, 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.

Animals↗
PubMed2004

Mechanisms underlying the gastroprotective action of glucocorticoids released in response to ulcerogenic stress factors.

Our previous results demonstrate the gastroprotective but not ulcerogenic action of glucocorticoids released in response to ulcerogenic stress factors. The present study was undertaken to investigate the possible mechanisms underlying the gastroprotective action of glucocorticoids in rat stomachs. The effects of deficiency of glucocorticoid production, with or without corticosterone supplementation, on blood flow velocity in gastric microvessels, microvascular permeability, mucus production, motility as well as gastric lesions were studied 3 to 4 h after the onset of ulcerogenic stimuli: water-restraint stress or indomethacin administration. The contribution of glucocorticoids in the healing process of gastric injury was also evaluated. The deficiency in glucocorticoid production significantly potentiated the functional disorders induced by ulcerogenic stimuli, such as a decrease in blood flow velocity and mucus production and an increase in gastric motility and in microvascular permeability, which resulted in aggravation of the formation of gastric lesions as well as impairment of their healing. The changes observed were prevented by supplementation of corticosterone at a dose mimicking a stress-induced corticosterone rise. We conclude that a gastroprotective action of glucocorticoids may be provided by multiple actions, including maintenance of the gastric mucosal blood flow and mucus production, attenuation of the enhanced gastric motility and microvascular permeability as well as beneficial influences on healing processes.

Animals↗
PubMed2003

Effect of adrenalectomy on healing of indomethacin-induced gastric erosions in rats.

We studied the effects of adrenalectomy and replacement therapy on healing of gastric erosions in adult Sprague-Dawley rats developed 4 h after subcutaneous injection of indomethacin in a dose of 25 or 35 mg/kg. Adrenalectomy was performed 1 week before or 4 h after indomethacin administration. Healing was evaluated by changes in the area of erosions over 24 h after indomethacin administration at fixed time intervals. Plasma corticosterone was measured. Adrenalectomy (irrespective of the time of intervention) decelerated healing of gastric injuries. Injection of corticosterone in a physiological dose of 4 mg/kg at the initial stage of healing (4 h after indomethacin administration) improved healing of erosions.

Adrenalectomy↗
PubMed2003

[Deficiency of glucocorticoid production delays the healing of acute gastric mucosal erosion and chronic ulcers in rats].

Effects of glucocorticoid deficiency followed by corticosterone replacement on the healing of gastric erosions and chronic gastric ulcers have been investigated in rats. Glucocorticoid deficiency was induced by adrenalectomy performed after the formation of gastric erosions or ulcers. Gastric erosions were produced by indomethacin (35 mg/kg, i.p.) or by 6 h immobilization at temperature 8 degrees C, chronic gastric ulcers were induced by 60% acetic acid. All ulcerogenic stimuli caused an increase in corticosterone production. Adrenalectomy created corticosterone deficiency and delayed the healing of gastric erosions and chronic gastric ulcers. The effect of adrenalectomy was more evident in the indomethacin ulcerogenic model. Replacement by corticosterone prompted the healing of gastric erosions and ulcers in adrenalectomized animals. These data suggest a participation of endogenous glucocorticoids in a restoration of gastric mucosal integrity.

Acetic Acid↗
PubMed2002

[Deficit of glucocorticoid production in rats aggravates ulcerogenic effects of stimuli of various modality and intensity].

Effects of glucocorticoid deficiency and corticosterone replacement on gastric mucosal injury induced by various ulcerogenic stimuli have been evaluated in rats. Gastric erosions were induced in male rats by stimuli of different modalities and intensities. Glucocorticoid deficiency was induced by adrenalectomy or delayed inhibitory action after a single pharmacological dose of cortisol (300 mg/kg, i.p.) injected one week before the onset of ulcerogenic stimulus. Ulcerogenic stimuli induced both a plasma corticosterone rise and a gastric mucosal injury. The area of mucosal damages induced various stimuli ranging from a small to extensive those. Glucocorticoid deficiency significantly potentiated an ulcerogenic action of each ulcerogenic stimulus. Replacement by corticosterone (4 mg/kg, s.c., 15 min before the onset of ulcerogenic stimulus) prevented or significantly decreased the erosion--potentiating effect of glucocorticoid deficiency. These results show that endogenous glucocorticoids released during ulcerogenic influences help gastric mucous membrane to resist against a harmful action of both weak and strong ulcerogenic stimuli.

Acetic Acid↗
PubMed2000

[The role of glucocorticoids in healing of indomethacin-induced lesions in the rat gastric mucosa].

Pretreatment with a single large dose of cortisol a week before indomethacin administration, or an adrenalectomy induced a glucocorticoid production deficiency in rats. The area of gastric erosions in these rats was considerably larger than in the control animals in 4, 24, and 48 hours after the indomethacin administration. Administration of corticosterone noticeably prompted the healing of the erosions in the rats with glucocorticoid deficiency. The findings suggest a gastroprotective effect of glucocorticoids in healing of indomethacin-induced mucosal injury.

Adrenalectomy↗
PubMed2000

[The role of endogenous glucocorticoids in maintenance of the gastric mucosa integrity].

Effect of glucocorticoid deficiency on susceptibility to gastric mucosal injury by non-steroid anti-inflammatory drugs (NSAID) was studied in rats. The corticosterone production was inhibited by a single large dose of cortisol as well as by an adrenalectomy. The drop in the corticosterone production prompted gastric erosions induced by the NSAID. Replacing corticosterone prevented the effects of cortisol pretreatment of adrenalectomy on NSAID-induced gastric erosions. The data obtained reveal a gastroprotective effect of endogenous glucocorticoids.

Adrenalectomy↗
PubMed1998

Corticosterone increase inhibits stress-induced gastric erosions in rats.

The role of glucocorticoids released in response to stress in the pathogenesis of stress-induced gastric erosions has been reevaluated. Gastric erosions elicited in male rats by 3-h cold-restraint or water-restraint stresses were studied after acute reduction of corticosterone release or occupation of glucocorticoid receptors by the antagonist RU-38486 during stress. Stress-induced corticosterone production was reduced by creating a lesion on the hypothalamic paraventricular nucleus (PVN) 4 days before stress as well as by pretreatment with a rabbit antiserum to adrenocorticotropin (ACTH) 30 min before stress. RU-38486 (10 mg/kg po) was administered 20 min before and 60 min after the onset of stress. Corticosterone for replacement was injected 15 min before the onset of stress to mimic stress-induced corticosterone response. Plasma corticosterone levels were measured by fluorometry or RIA. Gastric erosions were quantitated by measuring the area of damage. Four days after PVN lesion, stress-induced corticosterone release was decreased and gastric erosions were increased. Injecting corticosterone significantly attenuated the effect of PVN lesion on gastric erosions. The ACTH antiserum inhibited corticosteroid secretion in response to stress and markedly increased gastric erosions. The administration of the glucocorticoid/progesterone antagonist RU-38486 significantly potentiated the formation of stress-induced gastric erosions. These observations support the suggestion that glucocorticoids released during stress have a gastroprotective action rather than an ulcerogenic effect as was generally accepted.

Adrenocorticotropic Hormone↗
PubMed1996

[The antiulcer effect of corticosteroids and the blood flow in the gastric mucosa].

Intravital microfilming by means of dark-field contact epiobjective was used for investigation of the role of gastric microcirculation in antiulcerogenic action of corticosteroids in rats. Microvascular volume blood flow velocity was calculated from measurements of red cell velocity and vessel diameters. There was compared gastric submucosal and mucosal microcirculation as well as gastric ulceration after water-immersion stress in rats with normal function of hypothalamo-pituitary-adrenocortical (HPA) axis and in rats with insufficiency of corticosteroid production, induced by blockade of the HPA axis. The 3h stress induced gastric ulcerations, dilatation of mucosal microvessels and a significant decrease of volume blood flow in submucosal microvessels. These changes were greater in rats with blockade of HPA axis than in animals with normal corticosteroid production. Replacement corticosterone therapy decreased the effects of HPA axis blockade. Thus corticosteroids which are produced during stress restricted the reduction of volume blood flow in submucosal microvessels, the dilatation of mucosal microvessels as well as gastric ulcerations. These findings indicate that corticosteroids exert their antiulcerogenic action via the mechanism of improvement of gastric microcirculation.

Adrenal Cortex Hormones↗
PubMed1996

[Corticosteroids limit the decrease in blood flow velocity in the microvessels of the gastric submucosal layer during stress in rats].

To evaluate the influence of stress and corticosteroids on blood flow velocity in gastric submucosal microvessels it was used intravital microfilming by means of a dark-field contact epiobjective. The plasma filled "gap" in the continuous erythrocyte flow were used as the markers to measure linear blood flow velocity. In unstressed rats the linear blood flow velocity was equal to 2.0 +/- 0.08 mm/sec (156 microvessels, 6.4 +/- 0.14 micron in diameter), calculated volume blood flow--(6.9 +/- 0.48) x 10(-5) microliters/sec. Stress (water immersion and restraint) led to a decrease of blood flow velocity in microvessels to more than double. A stress-induced decrease of blood flow velocity was more greater in rats with insufficient corticosteroid production. The linear velocity of blood flow of these rats was lowered to 0.6 +/- 0.06 mm/sec, volume blood flow to (1.6 +/- 0.21) x 10(-5) microliters/sec. Replacement corticosterone therapy increased the blood flow velocity. It was concluded that stress decreases blood flow in microvessels of gastric submucosa. The results revealed that glucocorticoids take part in normalization of blood flow of gastric microvessels during stress and this action can provide antiulcerogenic effect of corticosteroids which was shown by us previously.

Adrenal Cortex Hormones↗
PubMed1996

[The adaptation-protective effect of corticosteroids on the rat gastric mucosa and its mechanism].

The influence of stress-induced corticosteroid production on gastric ulceration, blood flow velocity in gastric microvessels and blood pressure was studied in rats. The role of plasma corticosteroids was investigated by means of blockade of the pituitary-adrenocortical system (PACS) and following corticosterone replacement therapy (400 mu/100 g b.w.). The blockade which was induced by Fi. hydrocortisone administration (7 days before stress, 30 mg/100 g b. w.) resulted in an insufficient corticosteroid production. To evaluate the influence of corticosteroids on blood flow velocity in gastric microvessels of muscular, submucosal and mucosal coats it was used intravital microfilming by means of a dark-field contact epiobjective. Stress (water immersion + restraint) induces an ulceration, a decrease in the systemic arterial blood pressure (3 h after stress onset) and a decrease in blood flow velocity in the gastric microvessels (3 h after stress onset). In rats with insufficient corticosteroid production stress-induced ulceration, a decrease in blood pressure and gastric blood velocity were more greater than in rats with intact PACS. Replacement corticosterone therapy corrected all parameters. The results revealed that antiulcerogenic effect of stress-induced glucocorticoid production is realised owing to normalisation of gastric blood supply which is provided by an increase in systemic blood pressure.

Adaptation, Physiological↗
PubMed1995

[The long-term depression of the function of the hypothalamo-hypophyseal-adrenocortical system in rats].

Hypothalamo-pituitary-adrenocortical axis reactivity was studied in vivo and in vitro in 7 days after single administration of 30 mg/100 g body weight of hydrocortisone in rats. There were a blockade of stress-induced decrease of CRF-41 content in median eminence, and failure of increase of ACTH and corticosterone levels in the blood to stress in 7 days after hydrocortisone administration. A decrease of reactivity to ACTH was shown during incubation of adrenals from rats treated with hydrocortisone. 300 and 400 mg/100 g body weight of corticosterone s. c. imitates a stress-induced increase of corticosterone in the blood and can be used as replacement therapy. We conclude that high supraphysiological doses of glucocorticoids results in a decrease of reaction of hypothalamus, pituitary and adrenals to stress.

Adrenocorticotropic Hormone↗
PubMed1995

[Gastric stress ulcers: the protective role of hormones of the hypothalamo-hypophyseal-adrenocortical system].

The role of hypothalamo-pituitary-adrenocortical (HPA) axis in stress-induced ulceration is reviewed. The special attention is devoted to corticosteroids. It is discussed our hypothesis according to which a gastric ulcer formation after administration of high corticosteroid doses is due to the insufficiency of corticosteroid production as a result of suppression of HPA axis. The evidence strongly supports our hypothesis about antiulcerogenic property of corticosteroids. Gastric microcirculation, as main subject of antiulcerogenic action of glucocorticosteroids, is reviewed. Conclusion derived from the data that corticosteroids play defensive role during stress-induced ulceration and their action is provided by maintenance of gastric microcirculation.

Adrenal Cortex Hormones↗
PubMed1995

[The effect of stress and corticosteroids on the rate of blood flow in the microvessels of the gastric muscular coat of rats].

In order to evaluate the influence of stress and corticosteroids on blood flow velocity in microvessels of muscular coat of the stomach we applied intravital microfilming by means of a dark-field contact epiobjective. The plasma filled "gap" in the continuous erythrocyte flow were used as the markers to measure linear flow velocity. In unstressed rats the velocity was equal to 1.76 +/- 0.07 mm/sec (182 microvessels, 3.7-8.7 mu in diameter). Stress (water immersion and restraint) led to a decrease of blood flow velocity in microvessels to more than double. A stress-induced decrease of blood flow velocity was greater in rats with insufficient corticosteroid production. The velocity of blood flow in these rats was lowered to 0.62 +/- 0.04 mm/sec. Replacement corticosterone therapy increased the blood flow velocity. It was concluded that stress decreases blood flow in microvessels of muscular coat of the stomach as well as in microvessels of mucosa. The results revealed that glycocorticoids take part in normalisation of blood flow of gastric microvessels during stress.

Adrenal Cortex Hormones↗