N. S. Sapronov

Protective effect of taurine on rats with experimental insulin-dependent diabetes mellitus

Taurine had the hypoglycemic effect during experimental insulin-dependent diabetes mellitus and decreased the concentrations of glucose and fructosamine, and increased the contents of insulin, C-peptide, and glycogen in the liver. Studying the dynamics of structural changes in pancreatic tissue confirmed a positive effect of taurine on β-cell function. The protective effect of taurine manifested in the absence of morphological signs for alloxan-induced diabetes: decrease in the number and size of pancreatic islets, change in their distribution, reduction of β-cell count, and accumulation of homogeneous deposits in islets.

Effect of uridine on energy metabolism, LPO, and antioxidant system in the myocardium under conditions of acute coronary insufficiency.

Experiments on rats have shown that preventive treatment with uridine stabilizes energy metabolism in the heart under conditions of 60-min left coronary artery occlusion. The preparation also prevented antioxidant system dysfunction and LPO hyperactivation. 5-Hydroxydecanoate, a selective blocker of mitochondrial ATP-dependent K+-channels, abolished the protective effect of uridine, which attested to the involvement of these channels into mechanisms of the cardioprotective effect of the preparation. The elimination of intravenously administered uridine from the blood of animals with acute ischemia was accelerated in comparison with that in intact animals, which could suggest the participation of this nucleoside in the processes of activation of intracellular anti-ischemic defense mechanisms.

Effects of synthetic and plant-derived selective modulators of estrogen receptors on depression-like behavior of female rats

Effects of chronic (for 14 days) intramuscular injections of tamoxifen (10 mg/kg), klimadynon (Cimicifuga extract; 20 mg/kg), and genistein (10 mg/kg) on depressionlike state were studied in female rats under conditions of natural fluctuations of blood estrogen levels and ovariectomy. Chronic tamoxifen caused a pronounced depression, while chronic klimadynon and genistein exhibited a pronounced antidepressant effect in intact and ovariectomized rats.

Status of the "protein kinase CK2-HMG14" system in age-related amnesia in rats.

The experiments described here demonstrate that disruption of the phosphorylation of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class may be the cause of decreased gene expression in age-related cognitive deficits. Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24 months old) was accompanied by decreases in the synthesis of synaptosomal proteins and transcription in nuclei isolated from cortical, hippocampal, and striatal neurons. There was a decrease in chromatin protein kinase CK2 activity and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2. Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5-methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14 phosphorylation by protein kinase CK2, increased transcription, increased the synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged rats. Thus, activation of the “protein kinase CK2–HMG14” system is accompanied by optimization of synaptic plasticity in aged animals. The results provide evidence for the high therapeutic potential of protein kinase CK2 activators.

Effect of a Deficiency of Ceruloplasmin Copper in Blood Plasma on Copper Metabolism in the Brain

Copper deficiency in adult rats was induced by addition of silver chloride to the feed. The concentrations of silver, copper, iron, and zinc and relative activity of genes for copper transporting proteins and copper enzymes were measured in the cortex, cerebellum, hippocampus, amygdala, pituitary gland, and hypothalamus. Silver was accumulated only in the hypothalamic—pituitary system. These changes were accompanied by a decrease in the concentration of copper and increase in the contents of iron and zinc. Activity of genes for copper transport enzymes (high-affinity copper transporter; and two copper transport ATPases, ATP7A and ATP7B) and copper enzymes that were formed in the intracellular secretory pathway did not decrease in the brain of rats with copper deficiency. Relative activity of genes for intracellular copper enzymes (Cu2+/Zn2+ superoxide dismutase and subunit IV of cytochrome c oxidase), concentration of immunoreactive polypeptides of superoxide dismutase, and enzymatic activity of superoxide dismutase remained unchanged under these conditions.

Antiamnestic effect of α7-nicotinic receptor agonist RJR-2403 in middle-aged ovariectomized rats with Alzheimer type dementia

The effects of chronic combined treatment with α7-nicotinic cholinergic receptor agonist RJR-2403 (1.0 mg/kg intraperitoneally) or α7-nicotinic cholinergic receptor antagonist mecamylamine (1.0 mg/kg intraperitoneally) and 17β-estradiol (0.5 µg per rat intramuscularly) for 10 days on passive avoidance retention were studied in middle-aged (15 months) ovariectomized rats with experimental Alzheimer type dementia. Chronic treatment with RJR-2403 and 17β-estradiol had a pronounced antiamnestic effect under conditions of Alzheimer type dementia in middle-aged ovariectomized rats.

Effects of New Taurine Derivatives on Primary Immune Response in Rats

The effects of new taurine derivatives TAU-15 and TAU-60 with normal and branched alkyl chains, respectively, in a dose of 25 mg/kg on the primary immune response in rats were studied in rats. Intraperitoneal injections of test compounds for 24 days caused transient inhibition of immune reactions to thymus-dependent antigen, which was related to suppressed production of interleukin-1β playing a key role in antigen presentation. This effect was probably associated with activation of cortisol secretion. TAU-15 inhibited production of tumor necrosis factor-α and, therefore, prevented tissue damages. The immune response was normalized after withdrawal of these preparations.

Cerebroprotective Effect of a New Taurine Derivative during Cerebral Ischemia

A new taurine derivative chlorohydrate-N-isopropylamide-2-(1-phenylethyl)aminoethanesulfonic acid normalized energy metabolism, inhibited lipid peroxidation, and reactivated antioxidant enzymes in the brain of rats exposed to ischemia. This taurine derivative decreased the mortality rate of animals with ischemic changes in cerebral circulation. The test compound was more potent than piracetam in producing the cerebroprotective effect.

The Role of the Serotoninergic System in the Regulation of Thyroid Function in Old Rats

The effect of serotoninotropic substances with positive and negative effects on serum concentrations of thyrotropic hormone, total triiodothyronine, and total thyroxin was studied in old male rats. Chronic treatment with L-tryptophan and citalopram reduced serum level of total thyroxin in old intact animals and serum concentration of thyrotropic hormone in old thyrectomied rats. DL-p-chlorophenylalanine increased the serum concentrations of total thyroxin in old intact rats and in thyroidectomied animals treated with triiodothyronine. Chronic methysergide therapy was associated with reduction of serum concentration of thyrotropic hormone in old intact and old thyroidectomied rats and of total triiodothyronine in old intact animals.

Effects of intracerebroventricular administration of beta-amyloid on the dynamics of learning in purebred and mongrel rats.

The effects of intracerebroventricular administration of the beta-amyloid peptide fragment Aβ(25–35) on the dynamics of the acquisition of a conditioned reflex in a Y maze were studied in Wistar and mongrel rats. The dynamics of decreases in the number of errors were assessed using an exponential mathematical model describing the transfer function of a first-order system in response to stepped inputs using non-linear regression analysis. This mathematical model provided a good approximation to the learning dynamics in inbred and mongrel mice. In Wistar rats, beta-amyloid impaired learning, with reduced memory between the first and second training sessions, but without complete blockade of learning. As a result, learning dynamics were no longer approximated by the mathematical model. At the same time, comparison of the number of errors in each training sessions between the control group of Wistar rats and the group given beta-amyloid showed no significant differences (Student’s t test). This result demonstrates the advantage of regression analysis based on a mathematical model over the traditionally used statistical methods. In mongrel rats, the effect of beta-amyloid was limited to an a slowing of the process of learning as compared with control mongrel rats, with retention of the approximation by the mathematical model. It is suggested that mongrel animals have some kind of innate, genetically determined protective mechanism against the harmful effects of beta-amyloid.