Effect of stress and the antioxidant ionol on the biosynthesis of catecholamines and the content of dopamine in the heart and adrenal glands

The effects of a synthetic antioxidant ionol (dibunol) on the biosynthesis and content of catecholamines in the heart and adrenal glands were studied. It was shown that in stress a mobilization of catecholamine reserve is combined with a considerable increase in dopamine concentration. In conditions of physiological rest, ionol did not affect the studied indices of adrenal catecholamine biosynthesis, while in the heart it enhanced the dopamine synthesis and content. With ionol administration, stress did not suppress but, on the contrary, increased the neuronal uptake and noradrenaline biosynthesis, catecholamine concentration remaining practically unchanged. Simultaneously, a manyfold increase in the biosynthesis along with a considerable increase in the concentration of dopamine developed in both organs. The data obtained suggest that ionol realizes its stress-defensive effect to a great extent due to the activation of catecholamine biosynthesis and to a concomitant increase in dopamine accumulation.     

An electrophysiological study of the anti-arrhythmia effect of antioxidant ionol]

The paper describes the study of anti-arrhythmia effects of ionol. In isolated rabbit papillary muscle, ionol (a) had no effect on the depolarization-induced automaticity; (b) did not influence early afterdepolarizations: (c) delayed the onset of post-depolarizations initiated by Ca-overload and therefore inhibited the ectopic focal activity in myocardium. In isolated left auricles of rabbit, ionol suppressed the shortening of the excitation wavelength induced with adrenaline and thus protected the heart of reentry and consequent rhythm disturbances.     

The role of lipid peroxidation and myeloperoxidase in priming a respiratory burst in neutrophils under the action of combined constant and alternating magnetic fields

The enhancement of lipid peroxidation in neutrophils (the content of malonic dialdehyde increased by 10.2%) has been shown after a 1-h exposure to a combined constant (42 μT) magnetic field and a weak low-frequency magnetic field (1.0, 4.4, and 16.5 Hz; 860 nT) collinear to it. No correlation was found between this effect and the process of functional pre-activation (priming) of neutrophils as a result of the combined action of magnetic fields detected by chemiluminescence enhancement in response to the introduction of the bacterial peptide N-formyl–Met–Leu–Phe in the presence of luminol, since ionol (10 μM), an inhibitor of lipid peroxidation, did not reduce the neutrophil priming index in this case. Preliminary addition of histidine (0.1 and 1.0 mM), a singlet oxygen scavenger, also did not decrease the priming index. A myeloperoxidase inhibitor, sodium azide (0.1 mM), exerted a significant inhibitory effect on the chemiluminescence intensity of the neutrophil suspension; priming did not develop in the presence of this inhibitor after the action of combined magnetic fields.     

Effect of antioxidants on regeneration of protoplasts in the mycelial fungus Trichoderma reesei 6/16

The relative content of antioxidants in the mycelium of Trichoderma reesei 6/16 obtained by propagation of fungal protoplasts was shown to decrease (as compared to the initial culture taken for preparation of protoplasts) and restored only in the second generation of regenerated mycelium. In this respect, the effects of various antioxidants (beta-carotene, ascorbic acid, alpha-tocopherol, and ionol) on the frequency of regeneration of T. reesei 6/16 protoplasts were studied. beta-Carotene increased the viability of fungal protoplasts to the greatest extent. The effect of ascorbic acid depended on the presence of Fe ions. Ionol did not cause any measurable protective effect.     

Protective action of antioxidants on Escherichia coli cells immobilized in polyacrylamide gel

The object of this work was to find out whether antioxidants could be used for weakening the effect of free radicals on Escherichia coli cells immobilized in polyacrylamide gel. Some of the antioxidants soluble in lipids and water (ionol, Epigid, glutathione) protected the cells against the action of free radicals produced in the process of acrylamide polymerization, and increased the viability of the immobilized bacteria.     

Effect of beta-endorphin on G-cells in rats with experimental duodenal ulcer

Immunohistochemistry was used to study the changes in the number of G cells in the antral part of the stomach of rats (40 animals) with cystamine-induced duodenal ulcer treated with beta-endorphine. In the stomach of rats with cystamine-induced ulcer the number of G cells was discovered to be significantly increased, which was removed by an opioid peptide. Naloxone did not block the action of beta-endorphine. Thus, beta-endorphine changes the number of G cells, the drug action being not associated with opiate receptors.     

Direct effect of bombesin on pancreatic and gastric growth in suckling rats.

Bombesin stimulates growth of the stomach and pancreas in adult rats. Part of this effect is thought to be through the release of CCK following bombesin treatment. We studied the effect of long term administration of bombesin on the pancreas and stomach in suckling rats and examined the action of bombesin using specific CCK antagonist (CR-1409) and bombesin antagonists (GRP19-26, D-Phe19, Leu26CH2NHCOCH3 = cpd 17; L-686,095-001C002 = cpd 23). Rat pups (7-days-old) were given bombesin (20 micrograms/kg body wt. twice a day) or vehicle (1% gelatin) for 9 days. Bombesin stimulated pancreatic and gastric growth (tissue weight, total protein and DNA content all increased). Pancreatic trypsinogen concentration and content showed a 2-3-fold increase. CR-1409 at 6 mg/kg body wt., a dose that blocked the trophic action of CCK-33 when given to pups at similar ages, did not affect the bombesin-stimulated growth of the pancreas or the increase in trypsinogen level. At 2.4 mg/kg body wt., cpd 17 partially blocked and cpd 23 completely blocked the trophic effect of bombesin on the pancreas and stomach and the increase in trypsinogen level in the pancreas. RU-486, a type II glucocorticoid receptor antagonist, given at a dose sufficient to block the physiological action of glucocorticoid, had no effect on bombesin-stimulated growth of the pancreas. Thus, in vivo, bombesin acts directly on the neonatal pancreas and stomach.     

Method of studying the effects of pharmacological substances on work capacity of animals in hypobaric hypoxia

The method of the study of medical agent influence and biological active substances on duration of small laboratory animals swimming has been worked out excluding the air. For this purpose the animals were placed into altitude chamber, filled with water by 1/3 (one-third) of its volume being in antiorthostatic position on dipping into water. It has been established that at the altitude of 4000 (four thousand) meters high the rat swimming duration became shorter in comparison with their work under normal pressure in 2.5-4 times. Bemitil stimulating work in hypobaric hypoxia depresses it sharply. Bemitil stimulating influence on the rat efficiency did not appear with rising. Antioxidant substance ionol increased efficiency in normal conditions and in hypoxia AKS-85 adaptogenic compound increased swimming in the height duration to a greater degree, mildronat substance for efficiency restoration produced actoprotective influence.     

Disorders of the heart contractile function in chronic hemolytic anemia and their prevention

The coronary blood flow and heart contractile function were studied on rats with phenylhydrazine-induced chronic hemolytic anemia. The coronary blood flow in the animals' hearts was increased 2.5-fold, whereas the main parameters of contractile function were reduced but insignificantly. After the coronary blood flow dropped to the control level, the pressure and contraction rate fell by 40% and the relaxation rate diminished 2-fold. Thus, the enhanced coronary blood flow in the hearts of animals with hemolytic anemia appears to be a factor that compensates for the maintenance of myocardial contractility at the subnormal level. Administration of the antioxidant ionol, an inhibitor of lipid peroxidation, coupled with phenylhydrazine did not prevent the development of anemia but made the coronary blood flow descend in the hearts of anemic animal only by 80%. Since the iron-containing products of red cell dissolution activate lipid peroxidation during hemolytic anemia, this might play a role in the occurrence of heart muscle injuries. It is suggested that ionol prevents such injuries to a considerable extent, thereby preventing the development of compensatory enhancement of the coronary blood flow and heart contractile function disturbances during its normalization.     

Prevention of adrenaline-induced heart damage using the antioxidant ionol

Experiments on an isolated papillary muscle of the rat heart left ventricle have demonstrated that pretreatment with the antioxidant ionol prevents the disturbances of myocardial contractility caused by administration of a large dose of adrenaline. The data obtained are in agreement with the concept that the prophylactic action of antioxidants during stress is determined by the fact that they prevent activation of lipid peroxidation in the heart under the action of excess catecholamines.     

The effect of muscarinic and beta-adrenergic blockade on cysteamine-induced gastrin secretion by the isolated perfused rat stomach

Cysteamine-induced duodenal ulceration in rats is accompanied by increased circulating gastrin. Although cysteamine appears to exert a direct action on the gastrin cell some groups have provided evidence for an involvement of the autonomic nervous system. The current experiments were performed to determine whether beta-adrenergic or cholinergic (muscarinic) pathways are involved in the acute effect of cysteamine on gastrin secretion in the isolated perfused rat stomach. Cysteamine (1 mM) increased gastrin (IRG) secretion to a maximum ranging between 100% and 192% above basal. A cysteamine concentration of 5mM resulted in peak levels ranging between 150% and 1050% above basal. Addition of atropine or propranalol did not influence the responses obtained. The present results, therefore, do not support a role for either cholinergic or beta-adrenergic pathways in cysteamine-induced gastrin release at the level of the stomach and suggest that in vivo such autonomic effects are mediated extrinsically.     

Effect of radioprotectors on lipid peroxidation in liver microsomes induced by ultraviolet irradiation of the skin in rats

The modifying effect of radioprotectors (serotonin, cysteamine, ionol) on lipid peroxidation intensification of liver microsomes caused by rat skin ultraviolet radiation has been studied. A possible mechanism of action of these compounds on the investigated indexes during their preventive injection is under discussion.     

Effect of met-enkephalin and morphine on gastric secretion and blood flow

The effects of met-enkephalin and morphine on gastric acid and pepsin secretion and gastric mucosal and total blood flow were studied in anaesthetized dogs with an in vivo chambered secretion stomach preparation. It was found that both agents infused intraarterially caused an increase in histamine-induced acid and pepsin secretion and mucosal and total blood flow. The above responses were significantly blocked by naloxone and nalorphine. In the resting stomach both opiates did not induce secretory changes but they increased mucosal and total blood flow. Met-enkephalin and morphine were also effective after intravenous administration. Met-enkephalin but not morphine fails to stimulate acid secretion if given into the portal vein. The likely mechanism of action of opiates on gastric secretion is discussed and a hypothesis of existence of opiate receptors in the gastric wall is presented.     

Inactivation of bacteriophage PM2 during storage

The kinetics of bacteriophage inactivation in the medium that is optimal for its storage has been studied at temperatures from 4 to 55 degrees C. The plot of Arrhenius dependence of the constant of inactivation rate consists of the two linear parts with the energies of activation Ea = 25 kcal/mol for 4-37 degrees C and Ea = 91 kcal/mol for 37-55 degrees C. The DNA of inactivated bacteriophage remained mostly in superspiralized form and completely preserved its biological activity as tested by transfection in spheroplasts. The analysis of inactivation kinetics suggests ageing of virions cultivated at 4 degrees C. The addition of watersoluble antioxidant amoxipin did not change the inactivation kinetics. The addition of antioxidant ionol with twin-80 increased the inactivation that was paralleled by the bacteriophage DNA degradation.     

Action of natural and synthetic antioxidants on the electrical parameters and stability of natural and artificial membranes

The effect of antioxidants alpha-tocopherol and ionol on membranes of human red cells and bilayer lipid membrane (BLM) from azolektin has been studied. Ionol at concentration 4-10 mM induces the hemolysis of erythrocytes, the cells form changes are observed at concentration 2 mM alpha-tocopherol doesn't show the hemolytic properties at concentration 23 mM. The ionol concentration 1 mM doesn't change the form of the cells, but influence the passive electric parameters: the capacity (Cs) of erythrocytic membrane increases and the intracellular conductance (chi i) decreases. Tocopherol (3 mM) induces the decrease both Cs and chi i. The fast increase of membrane conductance is almost immediately registered on one side of BLM at addition of ionol (0,2-0,4 g/ml). Phosphatidylionol synthesized from ionol and contining the acyl chains C15H31 and C17H35 doesn't influence the electrical properties of BLM.     

胃壁肾上腺素能受体作用的分析

选用46只 Wistar 大鼠,分别观察了酚妥拉明和心得安对迷走神经完整和切断迷走神经大鼠胃内压的影响。结果为:酚妥拉明对迷走神经完整大鼠的胃内压没有影响,但能使切断迷走神经大鼠的胃内压明显下降,心得安可使去迷走神经和迷走神经完整大鼠的胃内压均升高,且两者无明显差异。结果表明:(1)支配胃的肾上腺素能神经紧张性作用主要表现为抑制;(2)β-受体可能仅位于胃平滑肌上,且介导抑制作用;(3)依赖迷走神经发挥作用的 α-受体介导抑制作用,而胃壁平滑肌上的 α 受体介导兴奋作用。     

The effect of phenobarbital, ionol and cAMP on the activity of glutathione metabolism enzymes in rodents

The phenobarbital and ionol administration to rats and mice increases considerably the glutathione transferase, glutathione reductase and gamma-glutamyl transferase activities in the liver. The induction of these enzymes has been observed in a number of experiments in the heart and kidney but it was less pronounced. A correlation was established between the induction of glutathione transferase, glutathione reductase and gamma-glutamyl transferase, their changes in mice and rats, phenobarbital and ionol effects. The stimulatory effect of cAMP on glutathione transferase in the liver (and in a number of experiments in the heart) increased against a background of the both agents. The cAMP-dependent activation of glutathione peroxidase was retained in the heart but in some series experiments it disappeared in the liver and kidney. Mechanisms of the long-term (induction) and short-term (cAMP) elevation of the glutathione transferase and glutathione peroxidase activities functioned independently and often in concord. It is suggested that induction of glutathione metabolism enzymes may play an important role in biological effects of ionol.     

Antiradical activity of retinal lipids under illumination

Antiradical activity (ARA) of lipids from cattle in norm and under strong illumination with and without antioxidants was studied by chemoluminiscence method of initiated ethylbenzol oxidation. Lipids ARA from the retina in norm was established to be sufficiently high-3.0 X 10(6) l/mol. s. alpha-tocopherol was proposed to be the main component influencing lipids ARA. Under strong illumination (15 min:, 0.8 J/s) lipids ARA decreased due to intensification of lipid peroxidation (the content of MDA was increased). The antioxidants (alpha-tocopherol, potassium phenozan, ionol) in 0.1 mM concentrations increased the ARA of lipids in spite of light action. Changes in overall inhibitory activity of natural antioxidants and MDA content was antibat.     

Effect of the antioxidant ionol on energy metabolic indices and heart function during acute hypoxia and subsequent reoxygenation

The effect of preliminary administration of antioxidant ionol on the heart energy metabolism and contractile function was estimated in hypoxic hypoxia and subsequent reoxygenation. The protective effect of ionol on the energy metabolism in hypoxia was shown to occur mainly at the level of glycolysis. In reoxygenation, the protective effect of ionol manifested at the level of creatine kinase system to provide a rapid restoration of the CP synthesis rate. This shift correlated with the velocity of restoration of the developed pressure and the velocities of contraction and relaxation. On the whole the data obtained correspond to the notion that creatine kinase system and ATP play an important role in the depression and subsequent restoration on the heart contractile function in acute hypoxia and reoxygenation and ionol provides more effective performance of this system and correspondingly more rapid restoration of the contractile function in reoxygenation.     

Mechanisms of retinal damage in chloroquine retinopathy

The paper presents the results of comparative electron microscopic, electrophysiological and biochemical studies of chloroquine effect on lipid peroxidation (LPO) both in vitro and in vivo (rabbits and rats). It has been shown that the progress of chloroquine retinopathy was not accompanied by the increment of the initial LPO level, and the use of ionol antioxidant did not protect the retina from the adverse effect of chloroquine. Besides, chloroquine was shown to suppress LPO in vitro. The results obtained substantiate the idea that LPO is not the primary mechanism in chloroquine retinopathy.