EXPRESSION AND ACTIVITY OF AMINOTRANSFERASES IN THE LIVER OF STREPTOZOTOCIN-DIABETIC RATS: THE EFFECT OF MIFEPRISTONE.

Context: Interventions that suppress hepatic gluconeogenesis from amino acids may be useful for improving glycemic control in diabetic patients.

Objectives: It was shown that administration of glucocorticoid receptor antagonist Mifepristone (MIF) leads to variously pronounced changes in the alanine-, aspartate-, tyrosine- aminotransferases (ALT, AST, TAT) activity in the liver of experimental animals. It has been suggested that this selective effect of MIF may be related to differences in the expression of the corresponding genes.

Effects Mifepristone on Aminotransferase Activities in the Liver in Rats with Streptozotocin-Induced Diabetes Mellitus.

The glucocorticoid status and activities of ALT, AST, and tyrosine aminotransferase in the liver are studied in rats with streptozotocin-induced diabetes mellitus in response to repeated intraperitoneal injections of mifepristone. Diabetic rats develop an increase of the blood corticosterone and liver aminotransferase levels in response to mifepristone. These results indicate that in diabetic animals the glucocorticoid hormones with high blood concentrations, increasing still more in response to mifepristone, overcome the receptor blockade, and realize their regulatory functions in hepatocytes.

Stress Response to Physical Exercise in Rats with Alimentary Obesity.

Stress response to physical exercise was studied in rats with alimentary obesity with and without caloric diet restriction. Daily excretion of corticosterone, progesterone, and testosterone, weights of internal organs, and serum levels of glucose, free fatty acids, triglycerides, corticosterone, and testosterone were estimated. Stress response to moderate exercise in rats with alimentary obesity was associated with predominance of anabolic influence of testosterone over the catabolic effects of corticosterone, which promoted the increase in the weight of reproductive organs.

Effect of Mifepristone on Corticosteroid Production in Vitro by Adrenal Glands of Rats with Streptozotocin Diabetes.

Changes in pregnenolone and corticosterone production by the adrenal glands of normoglycemic rats receiving the course of intraperitoneal mifepristone or NaCl administration were co-directed, but differed in magnitude. In rats with hyperglycemia, corticosteroid production increased after NaCl administration over 5 days and returned to the initial values after 15-day administration. On the contrary, pregnenolone and corticosterone production was suppressed after 5-day course of mifepristone, but significantly increased after mifepristone administration for 15 days.

Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals.

We studied the content of corticosterone and its precursors in the adrenal glands, corticosterone in blood serum and daily urine of rats, and activity of first and second isoforms of 11β-hydroxysteroid dehydrogenase in the liver and kidneys of rats after 15 daily intraperitoneal injections of 0.9% NaCl or glucocorticoid receptor blocker mifepristone in 0.9% NaCl.

Synchronization of the Estrous Cycle against the Background of Increased Excitability in Rats Selected for Catatonic Type of Reaction.

Selection for the elevation of catatonic type of reaction in female GC rats ("genetic" and "catatonia") was followed by an increase in the number of intense running episodes in response to acoustic stimulation. The observed changes are typical of increased general excitability in these animals. The phenomenon of estrous cycle synchronization was confirmed by variations in the concentrations of estradiol and progesterone in groups of Wistar and GC rats differing by the degree of synchronization.

[Comparative analysis of imipramine intake reactions in catatonic and wistar rats].

Chronic imipramine intake (7.5 mg/kg) leads to the stable decrease of excitable reactions to sound stimulant in Wistar rats and induced phase behavioral response in catatonic GC rats. Increased noradrenaline level in frontal cortex and striatum in Wistar animals was shown, whereas it didn't reveal noradrenaline level differences in any brain structures in GC rats.

Activity of 11β-hydroxysteroid dehydrogenase in the adrenal glands, liver, and kidneys of rats with experimental diabetes.

We studied activity of the key enzyme of the pre-receptor metabolism of glucocorticoid hormones, 11β-hydroxysteroid dehydrogenase, in rat adrenal glands, renal cortex and liver in the course of development of alloxan diabetes (9, 20, and 28 day). The enzyme activity was increased 3-4 fold in the adrenal glands throughout the experiment. At the same time, according to the adrenal gland level of corticosterone, its precursor 11-deoxycorticosterone and reversible metabolite 11-dehydrocorticosterone, activity of the second isoform of the enzyme dominated at the early stages of diabetes, and that of the first isoform, at later stages.

Production of corticosteroid hormones in vitro by adrenals in rats with streptozotocin-induced diabetes.

We studied baseline and ACTH-stimulated in vitro production of corticosteroids by rat adrenals. Production of the basic corticosteroids pregnenolone (early precursor in corticosteroid synthesis), progesterone (intermediate precursor in synthesis of gluco- and mineralocorticoid hormones), and corticosterone (major glucocorticoid hormone in rodents) in animals with streptozotocin-induced diabetes was enhanced by 1.8-2.

Rats of hypertensive ISIAH strain are resistant to the development of metabolic syndrome induced by high-fat diet.

We studied the influence of high-fat diet on the development of metabolic syndrome in rats of hypertensive ISIAH strain and normotensive WAG strain. In contrast to ISIAH rats, high-fat diet in WAG rats led visceral obesity, glucose tolerance, and dyslipidemia. DNA-binding activity of the peroxisome proliferator-activated receptor α (PPARα) decreased in the liver of WAG rats and increased in ISIAH rats.

Effect of mifepristone on glucocorticoid receptor gene expression in the liver of rats with streptozotocin-induced diabetes.

The effects of mifepristone on activity of the adrenocortical system, expression of glucocorticoid receptor gene, and tyrosine aminotransferase activity in the liver were studied in rats with streptozotocin-induced diabetes. Administration of glucocorticoid receptor blocker mifepristone to rats without diabetes was followed by a 1.9-fold increase in serum corticosterone concentration and a 1.

Adrenocortical system response to induction of inflammation with silicon dioxide in rats with alloxan-induced diabetes mellitus.

Alloxan-induced diabetes mellitus in rats was characterized by persistent increase in blood levels of corticosterone, while chronic granulomatous inflammation induced by silicon dioxide and its combination with alloxan-induced diabetes mellitus were associated with transient increase in blood corticosterone level followed by gradual development of hypoadrenocorticism. The content of corticosterone in the adrenal glands of rats with alloxan-induced diabetes mellitus remained unchanged in the dynamics of the disease, but the level of progesterone decreased at the early terms of diabetes and then returned to the initial values. After administration of silicon dioxide to intact rats and to rats with diabetes mellitus, changes in hormone content in the adrenal glands were observed only at the initial stages of inflammation and consisted in elevation of corticosterone concentration against the background of reduced progesterone content.

[Iodine availability, thyroid structure and function in residents of the city of Mirny, Republic of Sakha (Yakutia)].

Iodine availability for residents of the city of Mirny, Republic of Sakha (Yakutia), was estimated from urinary iodine and creatinine levels and their calculated ratio. Median of iodine/creatinine ratio in the groups of children and adults included in the study was 167.2 and 110.

Effect of imipramine on nerve excitability in GC rats.

Imipramine test (7.5 mg/kg) revealed a persistent positive reaction of Wistar rats, which manifested in reduced excitability of animals. Oral administration of imipramine solution was followed by unstable behavioral reactions in GC rats.

Functional state of adrenocortical system in rats with manifest alloxan-induced diabetes mellitus.

In the adrenals of male rats with manifest form of alloxan-induced diabetes mellitus (blood glucose >20 mmol/liter), the content of progesterone was higher by 1.6 times, deoxycorticosterone by 2.5 times, corticosterone by 3.

Content of steroid hormones in the blood and adrenal glands of mice in the dynamics of BCG- and SiO2-induced granulomatous inflammation.

Individual or combined administration of BCG vaccine and silicon dioxide to male mice induced a nonspecific stress response of the adrenal glands and gonads judging from changes in the concentration of blood cortisol and testosterone. The dynamics of cortisol concentration in the adrenal glands was similar, while changes in progesterone concentration were in antiphase to those in the blood. After combined administration of both inductors of granulomatous inflammation, changes in the concentrations of the studied hormones to a greater extent corresponded to their dynamics after injection of BCG.

Structural changes in the liver and content of steroid hormones in the blood and adrenal glands of mice with systemic candidiasis treated with a composition of amphotericin B and dialdehyde dextran.

In CBA mice infected with C. albicans, phasic pattern of granulomatosis development was observed. In all groups, the number of granulomas in the liver was minimum on day 56 after infection.

Effects of modified amphotericin in experimental systemic candidiasis.

Lysosomotropic composition of dialdehyde dextran and amphotericin B had a greater therapeutic effect in mice with systemic candidiasis compared to free amphotericin B. This composition normalized glucocorticoid function of the adrenal glands and decreased the severity of liver destruction at late terms of granulomatous inflammation.

Functional activity of the adrenal cortex in mice of opposite strains with candidiasis.

Experiments were performed on two opposite strains of mice differing in the basal blood glucocorticoid concentration in the blood. Infection of animals with C. albicans fungi led to the development of hypocorticism.

[Experience in the determination of iodine in the urine by the kinetic cerium arsenite method].

The authors describe the kinetic cerium arsenite method for measuring iodine in the urine using reagents made in Russia. The urine is prepared for analysis by wet calcination with a mixture of chlorous and perchloric acids. The method of synthesizing chlorous acid, preparing reagents, collecting urine, and procedure of analysis are described.

[Functional state of the thyroid gland in rats receiving an increased quantity of iodine with drinking water].

Thyroid and adrenocortical function was examined in rats fed increasing quantities of iodine with drinking water. No noticeable deviations in thyroid hormone levels were found in the blood of experimental animals. Thyroid hormone levels in thyroid tissue were changing in the same direction in the animals kept on various iodine diets, these changes depending on experiment duration: an increase of thyroxine and more so, of triiodothyronine was observed in 50 days, and reduction thereof in 90 days.