Comparison of antioxidant properties of nifedipine and illuminated nifedipine with nitroso spin traps in low density lipoproteins and phosphatidylcholine liposomes.

Illumination nifedipine, a calcium channel blocker, gives a nitroso-compound, 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridine-dicarboxylic acid dimethyl ester (NTP), which has spin trapping properties. The antioxidant ability of NTP was tested in a model of lipid peroxidation in low density lipoproteins (LDL) and phosphatidylcholine liposomes, and was compared with parent nifedipine and with other nitroso spin traps such as 3,5-dibromo-4-nitrosobenzene-sulfonic acid (BNTB), nitrosobenzene (NTB) and 2-methyl-2-nitrosopropane (MNP). Nifedipine (20-200 mumol/l) did not inhibit lipid peroxidation either in LDL on in liposomes, whereas its photolytical product NTP was found to be very effective at the same concentrations. The average antioxidant potencies of the nitroso spin traps were similar in both models and decreased in the order: NTP > or = BNTB > NTB > or = MNP. As detected by EPR spectroscopy, the studied nitroso compounds formed stable nitroxide radicals in a pseudo-Diels-Alder reaction, as a result of their interaction with unsaturated bonds of lipids in LDL and liposomes. The relative concentrations of thus formed radicals were in the order: NTP >> BNTB >> NTB approximately MNP and were related to their antioxidant properties. Thus it seems that the ability of the nitroso-compounds to form nitroxide radicals with unsaturated lipids may play a role in the antioxidant effect of these compounds.

Modulation of the hypolipidemic effect of fish oil by inhibition of adipose tissue lipolysis with acipimox, a nicotinic acid analog.

To assess the possible benefits of combined hypolipidemic therapy (acipimox+marine fish oil) on lipid and lipoprotein metabolism, male Wistar rats were fed for 14 days a high sucrose diet (70 cal% sucrose) alone or a high sucrose diet supplemented with acipimox (0.2 g/100 g diet) and/or fish oil (1 ml orally daily; 30 wt% of n-3 PUFA). Feeding a high sucrose diet increased (control: 61 +/- 6 vs HS: 110 +/- 8 nmol.min-1.mg-1, p < 0.001) the activity of acetyl CoA carboxylase in the liver, this was normalized by fish oil but not acipimox alone (HS+FO: 68 +/- 4; HS+ACI: 95 +/- 4; HS+ACI+FO: 71 +/- 2 nmol.min-1.mg-1). Increased triglyceride concentration in serum and muscle tissue (m. soleus and heart) of high sucrose-fed animals was suppressed equally by fish oil, acipimox, and/or both. The cholesterol-lowering effect of fish oil was also present in the liver (p < 0.005). The cholesterol-lowering action of acipimox was accompanied by the accumulation of cholesterol in the liver (p < 0.005), whereas the combination of acipimox+fish oil did not change the liver cholesterol content. After fish oil the LDL binding capacity of liver plasma membranes was increased 1.6-fold (p < 0.001). LDL receptor activity was significantly decreased in HS+ACI group (p < 0.05), but remained unchanged in HS+FO+ACI-fed animals. In summary, (a) the hypotriglyceridemic effect of fish oil in high sucrose-induced HTG is due to its inhibitory effects at the level of fatty acid synthesis; (b) decreased triglyceride production and output from the liver prevent triglyceride accumulation in muscle tissue; (c) the cholesterol-lowering action of acipimox but not fish oil was accompanied by an accumulation of cholesterol in the liver; (d) the latter phenomenon may be due to the opposite effects of both drugs on cholesterol catabolism via hepatic LDL receptors.

Relationship between the duration of the breast-feeding period and the lipoprotein profile of children at the age of 13 years.

Selected parameters of lipid metabolism were studied in a group of 76 children aged 12-13 years. The children were divided into 4 subgroups according to the duration of neonatal nutrition (no breast feeding, breast feeding for 3, 6 or more than 6 months). We studied the concentration of total serum cholesterol, its distribution into lipoprotein fractions, the concentration of serum triacylglycerols and apolipoproteins A1 (Apo A1) and B (Apo B). Atherogenic indexes were calculated from the data obtained. The highest cholesterol levels (5.20+/-0.15 mmol x l(-1)) were found in children who had been breast-fed for more than 6 months, while the highest concentrations of Apo B (0.80+/-0.07 g x l(-1)) and Apo A1 (1.76+/-0.06 g x l(-1)) and the highest Apo B/Apo A1 ratio (0.45+/-0.04) were found in children with the shortest period of breast-feeding. No significant sex-related differences in total, VLDL, LDL, HDL cholesterol, triacylglycerols and apolipoproteins were observed.

Late effects of early nutritional manipulations.

Effects of early neonatal interventions on metabolic parameters later in life (s.c. late effects) were studied in rats using two models; namely, (a) the effects of premature weaning and (b) the effects of "dietary" manipulations during the suckling period (s.c. small vs. large litters). (a) Premature weaning of rats caused an earlier degeneration of spermiogenesis and elevated plasma cholesterol levels in adult animals when compared to levels found in animals weaned 12 days later (on day 30 after birth). In adult rats, radioiodine uptake in thyroid glands was lower in the group weaned prematurely. Premature weaning was followed by a decrease of corticosterone production in adrenal glands in adult animals; in female adult prematurely weaned rats, an elevated response of adrenal cortex to stressors was observed. Several other studies explored the "immediate" effects of early, premature weaning. (b) Early exposure to high fat diet evoked a hypercholesterolaemic response in adulthood following brief exposure to HF diet. Rats from litters reduced to 3 or 4 pups per mother on postnatal day 3 exhibited 2 days later plasma levels of cholesterol higher than in rats raised in large litters of 8 or 14. The difference between small and large litters was preserved for the whole lifespan of the animals. In adulthood, rats from small litters were fatter and had higher levels of plasma cholesterol and insulin. Other studies suggester that early dietary experience may regulate the pattern of drug metabolism in adult life. An inhibition of diurnal plasma corticosterone variation was found in rats overfed during the neonatal period and an increased stimulation of lipolysis by norepinephrine and lipogenesis by insulin was demonstrated in neonatally underfed rats. Interesting studies were reported in longitudinally studies in children: at the age of 9-12 year breast-fed children (for more than 6 months) had the highest cholesterol levels; on the other hand significantly increased levels of APO B, Apo A1, ATH index and Apo/B Apo A1 quotient (p < 0.05) were found in the nonbreast-fed group (27 references).

Antioxidant and pro-oxidant effects of epinephrine and isoprenaline on peroxidation of LDL and lipid liposomes.

Antioxidant or pro-oxidant properties of epinephrine (EPI) and isoprenaline (ISO) were studied in the absence and presence of Fe2+, Fe3+ and Cu2+ ions. EPI and ISO (>2 micromol/l) inhibited peroxidation of low density lipoprotein (LDL) induced by 2, 2'-azobis(2-amidino-propane) (AAPH). EPI had a similar inhibitory potency as ISO, but their potency was several times higher than the potency of alpha-tocopherol (alpha-TOC). When the LDL peroxidation was induced by 5 micromol/l CuSO4, EPI and ISO enhanced LDL peroxidation at low concentrations (10micromol/l) and decreased peroxidation at higher concentrations (30 micromol/l). The compounds had a similar tendency to inhibit the peroxidation of phosphatidylcholine liposomes. EPI (3-30 micromol/l) inhibited lipid peroxidation of phosphatidylcholine liposomes induced by 2 mmol/l of AAPH, but it was less effective and even increased the peroxidation, when the samples contained 2 mmol/l AAPH with 50 micromol/l FeSO4 or 2 mmol/l AAPH with 20 micromol/l FeCl3. Inhibition of lipid peroxidation by EPI was also observed when studying decreased oxygen consumption, when the peroxidation of linoleic acid was induced by lipoxidase. In conclusion, EPI and ISO reduced lipid peroxidation, but they exhibit pro-oxidant properties in the presence of Fe2+, Fe3+ or Cu2+ ions, depending on the catecholamine and ionic concentration.

Nafazatrom inhibits peroxidation of phosphatidylcholine liposomes, heart homogenate and low density lipoproteins.

In order to contribute to the understanding of the biological properties of nafazatrom, an antithrombotic agent (NAP), we studied its effects on peroxidation of low density lipoproteins (LDL), lipid liposomes, heart homopgenate, and its interaction with alpha-tocopherol radical. NAP decreased the FeSO4 and H202-induced peroxidation of phosphatidylcholine liposomes and heart homogenate, and it decreased peroxidation of LDL induced by CuSO4 or 2,2'-azobis(2-amidinopropane). The antioxidant effect of NAF was about 3 times less potent than that of alpha-tocopherol (alpha-TOC) in phosphatidylcholine liposomes, and NAF was about 2-4 times more efficient to decrease peroxidation of LDL than alpha-TOC. Possible interaction of NAF with alpha-tocopherol radical (alpha-TR) was studied by EPR spectroscopy. NAF decreased the concentration of alpha-TR, but it was about 100-times less efficient than vitamin C. This may indicate that NAF does not interfere with alpha-TR formation and/or reduction of alpha-TR in biological system. The obtained results may help the explanation of biological effects of NAF.

Lipid metabolism in young males with hypotestosteronaemia and oligospermia prior to, during, and after treatment.

Relationships between plasma testosterone levels and selected parameters of lipid metabolism were studied in a group of young sterile males prior to, during, and after hormone therapy. Initial hypertriacylglycerolaemia and decreased concentrations of HDL cholesterol returned to normal values after 30 days of methyltestosterone administration. LDL cholesterol concentrations decreased significantly as did plasma apolipoprotein B levels. These changes persisted also one month after cessation of treatment. The results suggest that restoration of initially decreased testosterone levels in the studied group of sterile males is associated with the restoration of the lipid profile.

[Regulation of cholesterol metabolism with dietary addition of oyster mushrooms (Pleurotus ostreatus) in rats with hypercholesterolemia]. / Regulácia metabolizmu cholesterolu hlivou ústricovitou (Pleurotus ostreatus) v diéte u potkana s hypercholesterolémiou.

BACKGROUND: It is generally accepted that lowering of serum cholesterol levels reduces the risk of atherosclerosis. Identification and characterization of natural substances with hypocholesterolemic activity useful in dietetic prevention or treatment of hypercholesterolemia is still relevant in countries with persistent progression of hypercholesterolemia. Addition of oyster mushroom (Pleurotus ostreatus), an industrially produced wood-rotting fungus, to the diet effectively reduced cholesterol accumulation in serum and liver of rats fed a cholesterol diet. The aim of a series of experiments was to explain the biochemical mechanism of this effect. METHODS AND RESULTS: Male Wistar rats fed a cholesterol (0.3%) diet shortly after weaning for a period of 8-10 weeks were used in the experiments. The addition of 5% of dried oyster mushroom to the diet had following effects: reduction of cholesterol level both in serum (5.12 +/- 0.55 vs. 3.44 +/- 0.16 mmol/l, p < 0.02) and liver (241 +/- 12 vs. 113 +/- 11 mmol/kg, p < 0.001); redistribution of cholesterol in favour of high-density lipoproteins; reduced production of very-low-density lipoproteins (135 +/- 7 vs. 96.5 +/- 5 mumol/h/kg, p < 0.001); reduced cholesterol absorption (61.2 +/- 2 vs. 53 +/- 2%, p < 0.02) and reduced HMG-CoA activity in liver (137 +/- 16 vs. 86 +/- 9 pmol/min/mg proteins, p < 0.02). Simultaneously, an increase in 7 alfa-hydroxylase activity in liver (17 +/- 1 vs. 22 +/- 1 pmol/min/mg proteins. p < 0.02) and bile acid excretion (7 +/- 0.9 vs. 11 +/- 0.5 mg/day/rat, p < 0.02) was observed. (Values shown are means +/- SEM.) CONCLUSIONS: Biochemical mechanism of hypocholesterolemic effect of oyster mushroom on cholesterol-fed rats includes reduced production of cholesterol-rich very-low-density and low-density lipoproteins which principally determine cholesterol levels in serum. This effect is related to decreased absorption and biosynthesis of cholesterol together with increase in cholesterol catabolism and excretion of degradation products-bile acids.

[Lipoprotein profiles in 6-year-old children breast fed for different periods of time]. / Lipoproteínový profil sestrocných detí s rôznou dojceneckou výzivou.

The authors submit results of investigations of the lipoprotein profile in six-year-old children fed a different diet during infancy. It is the continuation of previous results of a long-term longitudinal investigation of this group of healthy children which revealed a favourable effect of breastfeeding on the cholesterol distribution in lipoprotein fractions. Throughout the investigation the children were divided into four groups according to the breastfeeding period. At the age of six serum cholesterol was assessed and cholesterol in lipoprotein fractions, levels of apolipoproteins A1 and B and risk for the genesis and development of atherosclerosis were calculated. The most favourable lipoprotein profile was found in the group of children, breastfed for three months and with this corresponded also the lowest values of the risk indexes. The serum cholesterol concentration, levels of serum apolipoproteins A1 and B in different groups of children did not differ significantly.

[The effect of different types of infant nutrition on indicators of lipid metabolism in 1-to-4-year-old children]. / Vplyv rôznej dojcenskej výzivy na niektoré ukazovatele tukového metabolizmu diet'at'a v období od 1. do 4. roka zivota.

The authors present the results obtained in investigations of the influence of different infant diets on some indicators of lipid metabolism in a group of healthy children followed up from birth and aged 1-4 years at the time of the investigation. The work is a continuation of previous investigations which provided evidence of the influence of breastfeeding on blood lipid levels and the cholesterol distribution in different lipoprotein fractions during the early postnatal period. The analysis of the plasma cholesterol and lipoprotein cholesterol in children breastfed for varying periods and children not breastfed bottlefed) at the age of 1, 1.5 and 2 years did not reveal substantial differences. The percentage ratio of cholesterol in different lipoprotein fractions in children aged 2 years and the risk indexes were, however, more favourable in children breastfed for the longest period. Similar results were recorded also in children aged 4 years. The apolipoprotein B plasma level which was assessed by immunoelectrophoresis was throughout the investigation higher in bottlefed children although the differences were not statistically significant.

Electrochemical control of a non-covalent binding between ferrocene and beta-cyclodextrin.

The forces required for the detachment of ferrocene (Fc) from ß-cyclodextrin (ßCD) in a single host (ßCD)-guest (Fc) complex were investigated using force spectroscopy under electrochemical conditions. The redox state of the guest Fc moiety as well as the structure of the supporting matrix was found to decisively affect the nanomechanical properties of the complex.

The role of hormones in the regulation of lipoprotein metabolism (review).

Atherosclerosis appears to be a disease with a multifactorial pathogenesis. The factors participating in its etiology are called risk factors [Fejfar 1972; Stamler 1983]. These may be divided into a group of uninfluencible risk factors (age, sex, genetic load, etc.) and influencible risk factors of first or second order. Hyperlipidemia may be considered as influencible risk factor of the first order [Goldstein et al. 1973]. From this reason it is necessary to investigate the etiology of lipoprotein metabolic disorders and the possibilities of their treatment and prevention. Hormonal influences are also considered to be one of the influencible risk factors which may affect a number of steps in lipoprotein metabolism.

Effect of short-term estrogen administration on some parameters of lipoprotein metabolism in male rabbits.

A follow-up of short-term administration of estrogens on certain parameters of the lipid metabolism in male rabbits has revealed significant changes in the distribution pattern of their cholesterol in the LDL (decline from 0.5 +/- 0.05 to 0.25 +/- 0.04 mmol l-1) and in the HDL fraction (increase from 0.22 +/- 0.02 to 0.5 +/- 0.02 mmol l-1), as also a striking increase of serum triglycerides (from 0.85 +/- 0.1 to 1.52 +/- 0.12 mmol l-1) and of triglyceride concentration in the VLDL lipoprotein fraction (from 0.09 +/- 0.06 to 0.65 +/- 0.11 mmol l-1) (P less than 0.05). The changes in the remaining indicators are not significant. The results obtained make it clear that even a short-term administration of estrogens significantly affects the lipoprotein profile in male rabbits, making it similar to that of females.