Search

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.

Development of Academician R. V. Chagovets' ideas of the regulatory role of vitamins and their derivatives in thiol-containing compound metabolism and antioxidant system formation as well as in studying non-coenzymatic functions of B-vitamins and vitamin-binding proteins had a considerable effect on the almost 40-year studies on pantothenic acid metabolism and biochemical functions by scholars at the vitaminologic school in Grodno. The concept concerning the intracellular structure of the pantothenate coenzyme form, CoA, pool (content and ratio of CoA-SH, acetyl-CoA, short-chain and long-chain acyls-CoA, coenzyme disulfide forms and CoA-S-S-proteins) was substantiated as an important metabolic regulatory factor (including glutathione system redox potential), with changes being a principal mechanism of pantothenate derivative vitamin and pharmacotherapeutic activity implementation. The effect of the latter is mediated through the systems of CoA biosynthesis and phosphopantetheine proteins, changed CoA-S-S-protein levels, which in turn maintain the intracellular level of CoA-SH as well as cytosolic and mitochondrial transport of its vitamin-containing precursors. A universal CoA biosynthetic function was revealed in prevention of lipid peroxidation initiation and oxidative stress development.

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.

Oxidation of derivatives and precursors of pantothenic acid was studied in alcohol dehydrogenase reactions. Despite the presence of free hydroxymethyl groups in a number of pantothenic acid derivatives only panthenol with Km = 8 x 10(-3) M was shown to serve as a substrate for alcohol dehydrogenase from horse liver tissue (EC 1.1.1.1) Pantethine, sodium phosphopantothenate, CoA and acetyl-CoA decreased the rate of ethanol oxidation, where pantethine and sodium phosphopantothenate were competitive inhibitors, while CoA and acetyl-CoA inhibited the enzyme noncompetitively Ki = 1.2 x 10(-2) M, 2.1 x 10(-2) M, 4.4 x 10(-4) M and 5.1 x 10(-4) M, respectively. Metabolic precursors, which were different from pantothenic acid in their structure, were not involved in the alcohol dehydrogenase reaction. Possible regulation of alcohol intoxication using derivatives and precursors of vitamin B3 is discussed.

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.

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.

Sixty-three patients with the typical variant of delirium tremens were examined. The results showed a marked reduction (by 8.7 times) in levels of coenzyme A (CoA) in leukocytes, which was indicative of deficiency of the coenzymic form of pantothenic acid (PA). Changes in CoA concentrations in leukocytes observed at the height of psychosis in patients with alcoholic delirium as compared to other parameters of PA metabolism have great significance for the assessment of vitamin metabolism. PA deficiency was more expressed in cases of long-standing and massive alcoholization which induces an earlier development of psychosis. CoA levels in leukocytes may be used as a parameter of detoxication processes in patients with delirium tremens. The data obtained are considered as indication for administration of PA drugs in combined detoxifying therapy of alcoholic psychoses.

The effect of calcium pantothenate (CPN)B 4'-phospho-CPN (PCP), pantetheine (PT) and calcium S-sulfopantetheine (SPN) on acute toxicity of kanamycin sulfate was studied on albino mice. The above derivatives of pantothenic acid except PT lowered the antibiotic toxicity. The coefficient of the antitoxic effect (LD50/ED50) of SPN and PCP was 1.3-1.4 times higher than that of CPN. The combined use of kanamycin (1/5 of the LD50) with CPN, PCP or PT (30 mg/kg bw was equivalent to CPN) for 15 days prevented the increase in the total content of CoA and in the content of the fraction of free CoA and the precursors of its biosynthesis participating in the reaction of N-acetylation in the liver and brain. The contents of these substances were within the normal during the whole experiment. A certain increase in the activity of pantothenate kinase in the liver cytosol due to the use of kanamycin was eliminated by the simultaneous use of PCP and PT. The vitamin-containing compounds PCP and SPN were recommended for the clinical trials as agents preventing complications of kanamycin therapy.

A radiometric procedure is developed for estimation of pantothenate kinase (EC 2.7.1.33) activity in various preparations of rat liver tissue; sodium 14C-D-pantothenate was used as a substrate and the reaction end product 4'-phosphopantothenic acid was measured. Optimal separation of the substrate and the end product was achieved by means of chromatography on DEAE-Sephadex A-25. 4'-phosphopantothenic acid was eluted from the column by 0.4 N HCl thus avoiding the label dilution and possible quenching of scintillation.

An ultrasonic interferometer has been used to study the process of fibrin clot lysis according to the decrease in the rate of propagation of an ultrasonic wave in the latter. A significant decrease in the sound fall rate on adding epsilon-aminocaproic and trans-4-aminomethylcyclohexanecarbonic acids to the system indicates their activity inhibiting fibrinolysis. N-nicotinoyl derivatives of this compounds possess less pronounced antiplasmin activity.

Study of the corticosteroid content in the adrenals and blood of rats under pantothenate deficiency has demonstrated a decrease in adrenocortical function. A single administration of pantothenate in a dose of 3.3 mg/kg reduced the influence of hypovitaminosis on the adrenals. The pantothenate derivatives (pantethine, 4'-phosphopantothenate and CoA in particular) injected to intact animals in a single dose equimolar to 3.3 mg/kg calcium pantothenate per kg bw had a marked steroidogenous effect.

Pantothenic acid metabolism and the status of energy processes in leukocytes were examined in 171 patients with hypertension and coronary heart disease. It was shown that the patients' body supply with the vitamin decreased as the disease progressed and heart failure supervened. The deficiency of pantothenic acid was shown to be interrelated with the impairment of energy processes. Application of pantothenate in a dose of 200 mg a day for two weeks led to the increased content of pantothenic acid and to normalization of energy processes.

The content of free and total pantothenic acid (PA) in the daily urine was studied microbiologically in 55 patients with virus hepatitis. At the height of the disease the excretion of the test vitamin forms with the urine noticeably decreased whatever the disease severity. During reconvalescence PA excretion rose because of the increase diuresis. However, the concentration of the vitamin in the urine did not reach normal. No disorders in PA metabolism were found in patients with hyperbilirubinemia of non-infectious genesis. Unlike normal subjects, oral administration of calcium pantothenate (50 ng) to patients with hepatitis results in a decrease of the excretion of the free form of PA. It is suggested that disorders in PA metabolism in patients with virus hepatitis are manifestations of functional vitamin deficiency which is a consequence of its reduced utilization.

White female rats received a balanced synthetic ration (control) or a ration devoid of pantothenic acid (PAA) during 3 weeks. After 36-hour fasting adaptive hyperlipogenesis was induced by feeding the animals with a high-carbohydrate ration, then [114-C]-PAA (sodium salt, 182 nmol/kg) was administered with intervals of 3, 6, 24 hours up to 1 hour before decapitation. Radioactivity of the rats' boiled liver extracts depended on the hyperlipogenesis stage, its level rose progressively, in the control and reached the maximum in PAA-deficient animals by hour 6 after the feeding resumption. The PAA-deficient animals possessed a high PAA-accumulating capacity of the liver and cytosole of the liver including non-covalent radionuclide binding by protein complexes. CoA-synthesizing capacity of the liver in the control animals, evaluated by the biotransformation of the labeled vitamin with CoA precursors of CoA, was intensified with the lipogenesis activation; in vitamin-deficiency CoA biosynthesis was accelerated more than two-fold as compared to the control at the initial and extended periods of hyperlipogenesis (3.6 h). The differences in proteinization and biotransformation of PAA in the liver of control and PAA-deficient animals disappeared by 25 h of adaptive hyperlipogenesis.

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.

Content of CoA and pantothenic acid in leukocytes as well as excretion of the vitamin derivatives, estimated by microbiological procedure, with urine with 6 and 24 hrs after administration per os or intramuscularly of 200 mg calcium pantothenate were studied in 42 donors and 25 patients with chronic alcoholism. In all the cases content of CoA of the pantothenate metabolites were increased in leukocytes within 6 hrs after the vitamin loading. Excretion of pantothenic acid and its derivatives with urine was increased for a short time in healthy persons after loading, however its total content maintained similar to normal values within 24 hrs. In the patients with chronic alcoholism the increase in concentrations of the components studied in leukocytes was accompanied by a distinct increase in excretion of the vitamin with urine within 24 hrs.

Alterations in the content and structure of CoA moiety typical of hyperlipogenesis (a rise in total and free CoA levels, a drop in short-chained fatty acyl-CoA/CoA and long-chained fatty acyl-CoA/CoA ratios) were found in the liver of obese mice with non-insulin-dependent diabetes (db/db). The treatment of diabetic mice with nicotinamide, an antilipemic drug, was accompanied by a decrease in total and free CoA levels and a rise in short-chained fatty acyl-CoA content and short-chained fatty acyl-CoA/CoA and long-chained fatty acyl-CoA/CoA ratios, probably leading to the inhibition of the enzymes of primary lipogenesis steps. It is suggested that CoA moiety structure is essential as an integral index regulating the rate of fatty acid biosynthesis in diabetes mellitus.

White rats kept on the B12-deficient diet for 9 weeks developed hyperchromic anemia, manifested the reduced content of cobalamines in the blood, kidneys, liver, myocardium and urine, the increased excretion of methylmalonic acid (MMA) and the intensified activity of CoA and its precursors participating in the reaction of acetylation in the liver, kidneys and myocardium. There was a decrease in the content of cobalamine-protein complexes that break down to the greatest extent at 80 degrees C. Ten-fold administration of cyanocobalamine (0.5 microgram/kg), calcium pantothenate (3.3 mg/kg) or of both the preparations concurrently removed the aforesaid disorders of cobalamine metabolism, with the most complete therapeutic effect being attained upon combined use of the vitamin preparations. Administration of pantothenate increased the content of cobalamines and cobalamine-protein complexes in the liver and myocardium, normalizing methylmalonylaciduria.