[Antioxidant status and glutathione redox potential of erythrocytes in patients with acute coronary syndrome].

Indicators of oxidative stress (OS), systemic inflammation, metabolism and redox status of glutathione (GSH) were investigated and compared in patients with ST-segment elevation myocardial infarction on electrocardiograms (STEMI), and patients with unstable angina (UA). The elevated and decreased myeloperoxidase level, superoxide dismutase activity, and moderate increased plasma levels of interleukin-6, while maintaining the antioxidant potential, were found in Group 1. Disorders in pro-/antioxidant balance and systemic inflammatory response were manifested in UA. Increased GSH concentration (and total GSH) in erythrocytes has been established for STEMI patients and the decreased GSH for UA patients. Thus, a significant shift of erythrocytes redox to oxidization and increase (unlike STEMI patients) of glutathione peroxidase activity were recorded. Mechanisms of the pro- and antioxidant functions of red blood cells in acute coronary syndrome are considered. The role of red blood cell glutathione to provide more oxidized intravascular environment for S-glutathionylation and optimization of redox signaling in target cells is pronounced.

Protection by pantothenol and beta-carotene against liver damage produced by low-dose gamma radiation.

Rats were exposed to a total dose of 0.75 Gy of gamma radiation from a 60Co source, receiving three doses of 0.25 Gy at weekly intervals. During two days before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body mass. The animals were killed after the third irradiation session, and their blood and livers were analyzed. As found previously (Slyshenkov, V.S., Omelyanchik, S.N., Moiseenok, A.G., Trebukhina, R.V. & Wojtczak, L. (1998) Free Radical Biol. Med. 24, 894-899), in livers of animals not supplied with either pantothenol or beta-carotene and killed one hour after the irradiation, a large accumulation of lipid peroxidation products, as conjugated dienes, ketotrienes and thiobarbituric acid-reactive substances, could be observed. The contents of CoA, pantothenic acid, total phospholipids, total glutathione and GSH/GSSG ratio were considerably decreased, whereas the NAD/NADH ratio was increased. All these effects were alleviated in animals supplied with beta-carotene and were completely abolished in animals supplied with pantothenol. In the present paper, we extended our observations of irradiation effects over a period of up to 7 days after the last irradiation session. We found that most of these changes, with the exception of GSH/GSSG ratio, disappeared spontaneously, whereas supplementation with beta-carotene shortened the time required for the normalization of biochemical parameters. In addition, we found that the activities of glutathione reductase, glutathione peroxidase, catalase and NADP-dependent malate (decarboxylating) dehydrogenase ('malic enzyme') in liver were also significantly decreased one hour after irradiation but returned to the normal level within 7 days. Little or no decrease in these activities, already 1 h after the irradiation, could be seen in animals supplemented with either beta-carotene or pantothenol. It is concluded that pantothenol is an excellent radioprotective agent against low-dose gamma radiation.

[Characteristics of pantothenic acid transport in membrane vesicles of the brush border of small intestine epithelial cells in rats]. / Kharakteristiki transporta pantotenovoi kisloty v membrannykh vezikulakh shchetochnoi kaimy épitelial'nykh kletok tonkoi kishki krys.

A microfiltration method was used to study the mechanism of pantothenic acid transport in the membrane vesicles of the rat small intestine brush margin. The vitamin uptake proceeded to inner space of the vesicles and was enhanced in presence of sodium ions. The findings suggest that the vitamin transport across the membrane of the small intestine brush margin is mediated by a carrier and proceeds via a Na(+)-co-transport mechanism.

Pantothenol protects rats against some deleterious effects of gamma radiation.

Rats were exposed to gamma radiation from a 60Co source, receiving 0.25 Gy at weekly intervals. During 2 d before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body weight. One hour after the third irradiation session, the animals were killed and their livers were analyzed. In animals not supplied with pantothenol, the irradiation resulted in a significant decrease of total liver lipids and a 50% decrease in phospholipids. Liver cholesterol was decreased by about 20%. Irradiation produced lipid peroxidation as expressed by doubling of the amounts of conjugated dienes and ketone dienes and of thiobarbituric acid reactive compounds. The amount of CoA in liver was decreased by 24% and that of reduced glutathione by 40%. The NAD+/NADH ratio was increased by 60% and the activity of NADP-dependent malate dehydrogenase (decarboxylating) was decreased by 26%. The amount of pantothenic acid and its derivatives (expressed as pantolactone-generating compounds) in blood decreased by about 80%. In rats to which pantothenol was administered, the content of pantothenic acid in blood was tripled compared to nonirradiated (control) rats, and all the biochemical parameters measured in liver were the same as in nonirradiated animals.

Some natural and synthetic antioxidants as stabilizers of beta-carotene conversion into vitamin A.

The effect of antioxidants (vitamins C and E, quercetin, probucol, butylated hydroxytoluene) on the oxidation of beta-carotene and its conversion into retinal under the influence of beta-carotene 15,15'- dioxygenase (CDO) from rat intestinal mucosa was studied. The activity of CDO decreased in the presence of oxidants. Antioxidants protected both the substrate and the enzyme. The extent of the protection depended on the antioxidant type. The combined injection of antioxidants and beta-carotene to animals completely or partially prevented the inhibition of the intestinal CDO which was caused by products of non-enzymatic oxidation of beta-carotene. Vitamins C and E, which protected the enzyme--substrate complex in vivo and in vitro, were found to be the most efficient protectors of beta-carotene conversion into retinal.

Noxious effects of oxygen reactive species on energy-coupling processes in Ehrlich ascites tumor mitochondria and the protection by pantothenic acid.

Irradiation of Ehrlich ascites tumor cells with ultraviolet light or exposure to the Fenton reaction results in lesions in the mitochondrial energy-coupling system. Formation of the membrane potential and its utilization for ATP synthesis are more affected than the respiratory chain. Preincubation of the cells with pantothenic acid or its derivatives which can serve as precursors of CoA largely protects against the damage of mitochondrial energetics by oxygen reactive species formed by UV light or the Fenton reaction. Incubation of Ehrlich ascites tumor cells with pantothenic acid increases their content of glutathione (most of which is present in the reduced form) by 40%. It is concluded that the protective effect of precursors of CoA against lesions of the mitochondrial energy-coupling system by oxygen reactive species is mainly due to removal of free radicals and peroxides by glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase.

Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation.

Preincubation of Ehrlich ascites tumor cells at 22 or 32 degrees C, but not at 0 degree C, with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine reduced lipid peroxidation (measured by production of thiobarbituric acid-reactive compounds) induced by the Fenton reaction (Fe2+ + H2O2) and partly protected the plasma membrane against the leakiness to cytoplasmic proteins produced by the same reagent. Pantothenic acid and its derivatives did not inhibit (Fe2+ + H2O2)-induced peroxidation of phospholipid multilamellar vesicles, thus indicating that their effect on the cells was not due to the scavenging mechanism. Homopantothenic acid and its 4'-phosphate ester (which are not precursors of CoA) neither protected Ehrlich ascites tumor cells against lipid peroxidation nor prevented plasma membrane leakiness under the same conditions. Incubation of the cells with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine significantly increased the amount of cellular CoA and potentiated incorporation of added palmitate into phospholipids and cholesterol esters. It is concluded that pantothenic acid and its related compounds protect the plasma membrane of Ehrlich ascites tumor cells against the damage by oxygen free radicals due to increasing cellular level of CoA. The latter compound may act by diminishing propagation of lipid peroxidation and promoting repair mechanisms, mainly the synthesis of phospholipids.

[Purification and various properties of pantothenate kinase from the rat liver]. / Ochistka i nekotorye svoistva pantotenatkinazy iz pecheni krys.

Homogeneous (according to disc gel electrophoresis data) ATP: D-pantothenate-4'-phosphotransferase (pantothenate kinase, EC 2.7.1.33) was obtained from rat liver cytosol of heterogeneous stock rats. The enzyme was purified 199-fold with a 9.3% yield. The enzyme was relatively unstable but retained its activity in the presence of 10% glycerol containing 5.10(-4) M ATP over 10 days at 4 degrees C. The pH optimum was 6.5; the apparent Km values were equal to 1.2 X 10(-5) M and 1.4 X 10(-3) M for pantothenate and ATP, respectively, at the ATP/Mg2+ ratio of 1. Pantetheine produced a competitive inhibition of pantothenate kinase. Pantethine or pantetheine disulfide did not inhibit the enzyme.

[Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non-insulin-dependent diabetes]. / Fermentnye sistemy substratnogo i kofaktornogo obespecheniia giperlipogeneza pri insulinnezavisimom diabete.

Enzymatic systems of hepatic hyperlipogenesis supply by substrate (acetyl-CoA) and cofactors (NADPH and ATP) were studied in experiments on diabetic C57Bl/Ks J mice (db/db) that served as a model of non-insulin dependent diabetes. The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered. Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis.

[Metabolism of pantothenic acid and its derivatives in animals deficient in this enzyme]. / Metabolizm pantotenovoi kisloty i ee proizvodnykh u zhivotnykh s nedostatochnost'iu étogo vitamina.

Distribution of [14C]labelled metabolites of pantothenic acid (PAA) has been studied in tissues of normal and PAA-deficient rats-weaners 6 h after single injection of the calcium pantothenate (PAA-Ca), calcium 4'-phosphopantothenate (PAA-Ca) or pantethine (PT) preparations. Essential differences in the intertissue distribution of vitamin derivatives to be injected are revealed against a background of a higher vitamin-retaining ability of the PAA-deficient tissues. A degree of radionuclides' biotransformation into CoA permits them to be arranged in the series: PPA-Ca greater than PAA-Ca greater than PT. In PAA-deficient animals which were injected labelled PPA-Ca up to 41% of the liver radioactivity is concentrated in the CoA fraction and the quantity of label in the composition of PAA-protein cytosolium complexes increases considerably. It is supposed that there is a special PAA-depositing system which provides the intracellular CoA biosynthesis.

[Acid-soluble CoA and free amino acid levels in the liver of pantothenic acid-deficient albino rats after separate and combined administration of panthotenic acid and cysteine]. / Uroven' kislotorastvorimogo KoA i svobodnykh aminokislot pecheni pantotenatdefitsitnykh belykh krys pri razdel'nom i sochetannom vvedenii pantotenata i tsisteina.

The feeding of white rats with a synthetic diet deprived of pantothenic acid (PAA) for 10 weeks led to a decrease in the content of acid-soluble CoA (AS-CoA) and to an increase in the liver taurine and glycine concentration. One hour after pantothenate injection (30 mg/kg) to PAA-deficient animals the level of AS-CoA rose by 96%, whereas after administration of an equimolar dose of cystein by 63%. Combined administration of CoA precursors did not result in summation of the effects. In all the cases of cystein injections, substantial changes were recorded in the structure of the liver amino acid pool, which were less marked if cystein was combined with pantothenate. It is assumed that the metabolism of cystein, glycine and, probably, that of alanine may depend on the changes in the CoA pool in hepatocytes.

[Quantitative gas chromatographic determination of pantolactone]. / Kolichestvennoe gazokhromatograficheskoe opredelenie pantolaktona.

A gas chromatographic procedure is described for quantitative estimation of alpha-hydroxy-beta 1 beta-dimethyl-gamma-butyrolactone (pantolactone). The chromatography was carried out using "LHM-8MD" apparatus equipped with a flame ionization detector. Columns with chromaton N-AW modified by 5% silicone XE-60 were used, helium served as a gas-carrier, chloroform - as a solvent, gamma-butyrolactone was introduced as a standard. High resolving power was achieved in experiments with the column for the analyzed substances and the standard at the sensitivity of the method 7.6 X X 10(-4) mmole/ml.

[Biosynthesis of the acetylation coenzyme in albino rat liver in the initial period of acute radiation sickness]. / Biosintez kofermenta atsetilirovaniia v pecheni belykh krys v nachal'nyi period ostroi luchevoi bolezni.

Mature albino rats were exposed to gamma-rays in a sublethal dose. A decrease of 22-35%, 13-39% and 29-37% was observed in the incorporation of 14C-pantothenate, 4'-phosphopantetheine and CoA, respectively, into the extracted fraction of free vitamin. After the first hour of observation specific activity of CoA decreased by 33% and corresponded to a decrease in the activity of ATP: D-pantothenate-4'-phosphotransferase.

[Peculiar features of the effect of cobalamines on the metabolism of vitamin B 12 and pantothenic acid in B 12 deficiency]. / Osobennosti deistviia kobalaminov na pokazateli obmena vitamina B12 i pantotenovoi kisloty pri B12-nedostatochnosti.

A single parenteral administration to B12-deficient rats of cyan cobalamine (CN-Cbl), oxycobalamine (OH-Cbl), methyl cobalamine (CH3-Cbl) and adenosyl cobalamine (Ado-Cbl) at a dose of 100 microgram/kg body weight increased the lowered level of total cobalamines in the liver to reach or exceed the norm. The study of cobalamine-protein complexes (CPC) in the liver of B12-deficient rats showed that the content of free cobalamines and CPC was decreased, the level of CPC degrading at 80 degrees C being particularly low. An administration of OH-Cbl and CH3-Cbl raised significantly the content of CPC degrading at 80 degrees C and presumably containing Ado-Cbl. Under the influence of cobalamines the increased activity of alpha-ketoglutarate dehydrogenase in hepatocytes returned to the normal and the CoA level declined only after administration of CN-Cbl and CH3-Cbl.