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Biomedical subjects

V V Frolkis

Publications and source records attributed to V V Frolkis.

At least 19 recordsLinked to original sources

Effect of enzyme imprinting of liver microsomal monooxygenases upon lifespan of rats.

Effect of the enzyme imprinting by phenobarbital upon alterations of hepatic microsomal monooxygenase activities and lifespan of Wistar rats has been studied. Phenobarbital-sodium (3.5 mg/100 g body weight per day, i.p.) was injected during 1-3 days after birth. This resulted in the enzyme imprinting of the liver microsomal monooxygenases, however, this effect being observed in female but not male rats. In the phenobarbital treated female rats of different age the duration of sleeping time was significantly lower than that in control animals, whereas it did not differ substantially in male rats. The cytochrome P-450 content increased by 34.5% in phenobarbital treated female rats in the age of 12 months in comparison with control animals. A mean lifespan of experimental female rats increased by 17.5% compared to the level of control animals and did not change in male rats. The analysis of survival of animals in Gompertz equation coordinates showed that enzyme imprinting by phenobarbital caused changes in the mortality patterns at different stages of ontogenesis in experimental female but not male rats. An inverse correlation was found between the duration of pentobarbital sleeping time and lifespan of female and male rats.

Aging↗

Peculiarities of axonal transport of steroid hormones (hydrocortisone, testosterone) in spinal root fibres of adult and old rats.

The labelled steroid hormones [3H]hydrocortisone and [14C]testosterone, being injected into the gray matter of the rat spinal cord L5-L6 segments, were shown to be transported at a high velocity along the ventral (anterograde) and dorsal (retrograde) root fibres. The maximum velocity of axonal transport along the ventral and dorsal roots in adult rats was, on average, 3006 +/- 101 and 3028 +/- 48 mm/day for [3H]hydrocortisone and 4594 +/- 186 and 5185 +/- 485 mm/day for [14C]testosterone, respectively. In old rats, axonal transport of steroid hormones was markedly slower. Its maximum velocity along the ventral and dorsal roots averaged to 756 +/- 64 and 738 +/- 48 mm/day for [3H]hydrocortisone and 624 +/- 54 and 608 +/- 80 mm/day for [14C]testosterone, respectively. In old rats the amount of labelled hydrocortisone incorporated into the ventral root fibres was sharply reduced (by more than an order of the value) as compared to that in adult animals. At the same time, the intensity of the labelled testosterone incorporation into the ventral root fibres did not demonstrate any significant age-related difference. The injection of low doses of steroid hormones (from less than one microgram to a few micrograms) into the lumbar spinal cord resulted in a significant hyperpolarization several hours later first of the gastrocnemius and then of deltoideus muscle fibres. In old rats, such a hyperpolarization occurred much later. It is suggested that axonal transport of steroid hormones is one of the mechanisms responsible for the effects of hormones on the tissues, which undergoes considerable changes with ageing.

Aging↗

Effects of partial hepatectomy on the plasma membrane status and the invertor mechanism of the hepatocyte Na,K-ATPase activity regulation in rats of various age.

The experiments were performed on adult (6-8 months) and old (22-24 months) Wistar rats. Insulin induced plasma membrane hyperpolarization and hepatocyte Na,K-ATPase activation in adult but not in old sham-operated rats. Partial hepatectomy had no effect on the invertor mechanism of Na,K-ATPase activity regulation in the liver of adult rats, while pronounced changes took place in old animals 4 weeks after partial hepatectomy. Insulin induced hyperpolarization in hepatocyte plasma membrane and activation of Na,K-ATPase both in old and adult hepatectomized rats. Invertors, intracellular regulators of the plasma membrane status, played an important role in the mechanism of this insulin-induced hyperpolarization. Four weeks after partial hepatectomy in old animals, the invertor mechanism of hepatocyte plasma membrane regulation appeared again, as well as membrane Na,K-ATPase capability to react to insulin action.

Aging↗

Age peculiarities of changes in the contractile function of isolated rat hearts during prolonged perfusion.

The experiments on the isolated hearts from adult and old rats have shown that during first hours of prolonged perfusion the contractile function decreased to a greater degree in adult rats compared to the old. Following a 3-h perfusion, there occurred a marked fall of the contractile function in old animals. The creatine phosphokinase activity in a perfusate grew sharply in the old rats and changed insignificantly in the adult. The Na,K-ATPase got activated in adult rats, which was prevented by the preliminary injection of actinomycin D, and declined in the old. It appeared that adult hearts had a better endurance of prolonged perfusion and kept sustaining a definite level of performance almost twice as long as the old. Under prolonged perfusion conditions, there has been synthesized a regulatory factor (invertor) in the heart of adult animals, which reduced the myocardial contractile function. The latter was evidenced from a fact that perfusate from adult hearts 'donors' promoted the decrease of contractility of the adult hearts 'recipients'. The preliminary injection of actinomycin D to adult rats prevented a developing decrease of the contractile function but did not induce any changes in the old. This permits to conclude that synthesis of the regulatory peptide factor promotes an economization and adaptation of the adult animal heart.

Aging↗

Effect of implantation of human apoAI gene on apoprotein composition and vasoactive properties of high-density lipoproteins in rats at different ages.

Transfer of human apoAI gene, within the molecular construction which provides its expression, to the liver of adult and aged rats resulted in the appearance of human protein in their blood, and was accompanied by changes in the content of high-density lipoproteins, as well as by the shifts in their protein and lipid composition. Administration of the human ApoAI gene was followed by changes of the vasoactive effects of HDL. Gene implantation is capable of enhancing the direct vasodilatory effects of HDL in old animals, being weakened by ageing, even against the background of normal age changes in the vascular wall tone.

Aging↗

Blood lipoproteins and their effect on contractile function of vessels in rats of different age.

Experiments on adult and old rats have shown that blood lipoproteins (LP) exert a dilatatory effect on isolated-segments of the thoracic aorta in animals of different age. In old versus adult animals, the sensitivity of vessels in all LP fractions (LDL, VLDL and HDL (low, very low and high density LP)) was lower as a result of age changes in the reactivity of vessels. The capacity of HDL to produce a vasodilatory effect decrease with age, which may be linked to changes in the lipid and apolipoprotein composition. The results revealed a decrease in the level of phospholipids and an increase in the amount of total cholesterol in HDL observed in old age. The capacities of LDL and VLDL to exert a vascular dilatatory action remained unchanged with age.

Aging↗

Invertors mechanism of the influence of insulin on the condition of plasma membranes of myocardiocytes in animals of different age.

Effect of insulin on Na, K-ATPase activity and phospholipid (PL) composition of myocardiocytes' plasma membrane (PM) was investigated in adult (6 months old) and old (28 months old) male Wistar rats. Administration of insulin increases Na, K-ATPase activity and phosphatidilethanolamin content, and decreases phosphatidilinositol content of myocardiocytes' PM in adult animals. Administration of insulin doesn't change Na, K-ATPase activity and decreases phosphatidilethanolamin content of myocardiocytes' PM in old rats. In the experiments with cellular hybrids (cytosol + PM) it was found that cytosol of adult insulin-treated animals caused the activation of Na, K-ATPase in both adult and old rats. Cytosol of old animals did not influence enzyme activity either in old or adult animals. Actinomycin D inhibited a stimulating insulin effect on Na, K-ATPase activity. The obtained data may suggest the presence of insulin-induced synthesis of intracellular factors responsible for resultion of the state of PM invertors.

Aging↗

Changes in the plasmatic membrane characteristics during microsomal monooxygenase induction in the liver of adult and old rats.

The experiments on adult (6-8 months) and old (24-26 months) male Wistar rats have shown that treatment of animals with phenobarbital results in a significant increase in hepatic microsomal enzyme content, plasmatic membrane Na+, K(+)-ATPase activities and the elevation of hepatocyte membrane potential value. It is presumed that the changes in plasmatic membrane characteristics during microsomal monooxygenase induction are related to the synthesis of specific intracellular factors (invertors). This assumption was verified by the experiments with 'cellular hybrid' system (cytosol--plasmatic membranes). Using this cross-systems, it was shown that the hepatocyte cytosol of rats treated with phenobarbital produced Na+, K(+)-ATPase activity. The extent of Na+, K(+)-ATPase activation was essentially lower when cytosol derived from old rat hepatocytes was used. The presence of specific factors that activated Na+, K(+)-ATPase in hepatocyte plasmatic membrane was also discovered in blood serum of induced adult and old rats.

Aging↗

Stress-age syndrome.

With aging a set of neurohormonal, tissue and cellular changes develop which can be defined as stress-age syndrome. They include irregular changes in the excitability of structures of the limbic system and hypothalamus, rise of the blood concentration of catecholamines, vasopressin, ACTH and cortisol, fall of the concentration of testosterone, thyroxin and other substances, change of the concentration of opioid peptides, immunodepression, dyslipoproteidemia hypercoagulation and free-radical damage of cells. One group of components of the above syndrome is of adaptive importance, while the other is damaging. Symptoms of stress-age syndrome have their individual peculiarities and cannot explain the whole complexity of symptoms of the organism's aging. Against the background of stress-age syndrome the course of developing stress reactions undergoes a change.

Adaptation, Physiological↗

Plasmic membranes of hepatocytes and adrenocorticocytes in rats of different ages: effect of testosterone.

Experiments on adult (6-8-month-old and 26-28-month-old) Wistar rats revealed the hyperpolarization of plasmic membranes and activation of Na,K-ATPase of adrenocorticocytes in animals of both age groups and of hepatocytes of adult rats. No effect of testosterone was observed on the level of membrane potential and the activity of Na,K-ATPase of hepatocytes of old rats. The effect of testosterone was prevented by inhibitors of protein biosynthesis (actinomycin D and cycloheximide) and a specific inhibitor of Na,K-ATPase (ouabain), but not by K(+)-channel blocker 2-aminopyridine. Testosterone was assumed to synthesize the specific factor, capable of activating Na,K-ATPase of plasmic membranes. The cytosole of hepatocytes and the blood serum of adult testosterone-treated rats activated the Na,K-ATPase of isolated plasmic membranes of hepatocytes of adult and old intact rats. During aging there was a decrease in the capacity of cells to synthesize the specific factor, which activated Na,K-ATPase of plasmic membranes.

Adrenal Cortex↗

Syndromes of aging.

Syndromes of aging are classified according to the rate of their development and the sequence of aging of different systems within an organism. Syndromes of aging are characterized by individual and populational specifics. Determination of syndromes of accelerated aging or retarded aging permits the prediction of age pathology development and life span. Comparison of aging peculiarities in animals with different species-specific life spans permits the definition of species-specific changes, chronobiological changes that correlate with chronobiological age, ontobiological changes that correlate with biological age, and parameters that do not change with age. Different correlation of the above parameters forms the basis for species-specific variations in the aging process. Neurohumoral shifts observed in aging are identical to stress effects, and therefore may be referred to as the stress-age syndrome.

Aged↗

Potential-dependent Ca channels of neurons in the mollusc Lymnaea stagnalis in aging: effect of norepinephrine.

During aging changes occur in the function of potential-dependent Ca channels of plasmic membrane of identified neurons in the mollusc Lymnaea stagnalis, i.e. the value of Ca inward current of neurons in old vs. adult molluscs was much higher at holding potential -50 - -30 mV. When held at -20 mV, the amplitude of Ca current decreased in the neurons of old molluscs, but continued to increase in those of adult molluscs. Various populations of potential-dependent Ca channels are assumed to have irregular age-related changes. The norepinephrine-induced inhibition of Ca current was more significant in old vs. adult molluscan neurons.

Aging↗

Synthesis of insulin-dependent activator of hepatocyte plasmatic membrane Na,K-ATPase decreases in aging.

The experiments on Wistar rats of different age-groups have shown that insulin (1.6 units/kg) provokes hyperpolarization of hepatocyte plasmatic membranes in adult rats, but not in old ones. The hyperpolarization can be prevented by actinomycin D and ouabain, while 2-aminopyridine is ineffective in this case. The appearance of hyperpolarization correlates with the activation of Na,K-ATPase in hepatocyte plasmatic membrane. It is shown that insulin injection provokes the appearance of Na,K-ATPase activation factor in the hepatocyte cytosol. The synthesis of this factor reduces with age.

Aging↗

Age-dependent effects of ischemia and reperfusion on cardiac function and Ca2+ transport in myocardium.

Experiments on isolated hearts from adult and old rats have proved an age-dependent decrease in the resistance of contractile function and cardiac rhythm to ischemia and reperfusion. The restriction of coronary flow by 70% produced significant changes in various links of the Ca2+ transport system (an increase in sarcolemmal permeability for Ca2+ and a decrease in Ca(2+)-accumulating capacity of sarcoplasmic reticulum included). These changes, more marked in old animals, seemed to play an important role in the mechanisms of disturbances in cardiac function following coronary insufficiency.

Aging↗

Peculiarities of neural regulation of the thyroid, adrenocortical and testicular functions in old age.

The age changes of neural control over the function of the thyroid, adrenal cortex and testicles were examined in adult (6 months) and old (28 months) male rats. In old age, there was a weakening of adrenergic control of thyroidogenesis, alpha-adrenergic and M-cholinergic control of glucocorticoid function of the adrenal cortex and reduction of adrenergic and M-cholinergic influences in the regulation of steroidogenic function of the testicles.

Adrenal Cortex↗

Age-related changes in the function of somatic membrane potassium channels of neurons in the mollusc Lymnaea stagnalis.

The function of the membrane potassium channels of the identified neurons of the small parietal ganglion was investigated in the adult (10-12-month) and old (22-24-month) molluscs Lymnaea stagnalis. Old molluscan neurons showed a decrease in maximal amplitude of fast and delayed potassium currents, in maximal potassium conductance, and in kinetics of inactivation of the delayed outward current. These features may be conditioned by the age changes in phospholipid composition of the membranes, rather than by the shifts of neuronal surface area during aging. Age dynamics in the function of potassium channels is thought to cause changes in the neuronal function.

Aging↗

Effect of enterosorption on animal lifespan.

Experiments were performed on Wistar male rats, starting from the 28th month of age. The effect of dietary sorbent (non coated nitrogen-containing carbon administered as 10 day courses at 1 month intervals in dosage of 10 ml/kg) on lifespan and a number of biological indices were studied. Enterosorption resulted in the increase of mean and maximal lifespan by 43 and 34% respectively. Analysis of the effect of enterosorption on activity of microsomal enzymes, intensity of total RNA and protein biosynthesis, lipid metabolism, formation of free radicals etc. showed that it produced a positive influence on the functional state of the studied systems and increased the organism's adaptive capacities. Enterosorption was found to delay the rate of onset of age-related structural changes in the organs and tissues.

Aging↗