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. The aim of the study was to investigate the gene expression and activity of ALT, AST and TAT in the liver of rats with streptozotocin-related diabetes (StD) under the long-term oral MIF administration. Methods: Male Wistar rats (n=48) with StD under the 10-days oral MIF administration were used. It was measured the activity of ALT, AST, TAT enzymes and relative expression of this genes in the liver of experimental animals. Results: In rats with StD the gene expression of all three studied aminotransferases in the liver was statistically significantly increased and their activity was increased as well. MIF administration did not change the studied genes expression and enzymes activity to healthy rats and caused a decrease in expression of ALT and AST genes and activity of these enzymes to rats with StD. However, the expression of the TAT gene and the activity of this enzyme in the liver of rats with StD increased upon MIF administration in comparison with animals with StD. Conclusions: The introduction of MIF against the background of StD reduces the expression of genes and the activity of ALT and AST in the liver, what determine the transamination of amino acids to include them in gluconeogenesis, but increases the expression of genes and the activity of TAT, what determine the inclusion of tyrosine in the biogenic amines synthesis. The mechanisms of such selectivity require further study.

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. Intraperitoneal mifepristone administration almost completely abolished the response of rat adrenal glands with normo- and hyperglycemia to ACTH in vitro; this effect did not depend on the duration of administration.

[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. The higher blood corticosterone concentration was decreased under antidepressant reaction in GC rats. Differences between intact GC animals were found out: reduced triglyceride level, lesser body weight, and greater weight index of adrenals in comparison with Wistar rats. Various mechanisms of imipramine action in two rat strains were shown: influence on adrenergic brain system, taking part in the control of exiting behavior in Wistar rats and reaction in adrenals in GC rats.

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. Blood levels of TNF-α, IL-6, and corticosterone increased more significantly in WAG rats. Corticosterone content in the adrenal glands was more markedly reduced in WAG rats. High-fat diet had no effect on BP in ISIAH and WAG rats. It was concluded that ISIAH rats can be used as a genetic model in studies of the mechanism of resistance to the metabolic syndrome.

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.

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. Norepinephrine concentration in the cortical and limbic regions of these animals remained unchanged, while plasma corticosterone concentration decreased to the control level and did not differ from that in Wistar rats. Our results indicate that imipramine has a modulatory effect on destabilization of the adaptive system in catatonic GC rats.

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. Treatment with free amphotericin B and its composition with dialdehyde dextran (CA) reduced the number of infiltrations and granulomas in the liver, the changes were more pronounced in animals receiving CA. A different pattern of cyclic fluctuations of cortisol content in the blood and adrenal glands and progesterone content in the adrenal gland was observed. By the end of observation (day 84), cortisol content in the blood and adrenals of mice treated with CA was considerably lower than in untreated mice and animals receiving amphotericin B.

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.

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 3.3 times, and 11-dehydrocorticosterone by 1.8 times than in the adrenals of control animals. Increased concentration of corticosterone and 11-dehydrocorticosterone were also found in the serum of rats with alloxan diabetes, but the difference between the experimental and control groups by these parameters was less pronounced compared to parameters in the adrenal glands.

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. C57Bl/6 and CBA mice with progressive candidiasis showed a persistent and phasic course of hypocorticism, respectively.