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Biomedical subjects

N Skottová

Publications and source records attributed to N Skottová.

At least 19 recordsLinked to original sources

Antioxidant status, lipoprotein profile and liver lipids in rats fed on high-cholesterol diet containing currant oil rich in n-3 and n-6 polyunsaturated fatty acids.

Plant-based n-3 polyunsaturated fatty acids (PUFA) possess a prospective antiatherogenic potential. Currant oil from Ribes nigrum L. is one of the few plant oils containing PUFAn-3 (15.3 mol%) in addition to PUFAn-6 (60.5 mol%). This study was aimed at comparing the effects of currant oil with those of lard fat, rich in saturated (43.8 mol%) and monounsaturated (47.0 mol%) fatty acids, on antioxidant parameters, the lipoprotein profile and liver lipids in rats fed on 1 % (w/w) cholesterol diets containing either 10 % of currant oil (COD) or lard fat (LFD). After 3 weeks of feeding, the COD induced a significant decrease in blood glutathione (GSH) and an increase in Cu(2+) induced oxidizability of serum lipids, but did not affect liver GSH and t-butyl hydroperoxide-induced lipoperoxidation of liver microsomes. Although the COD did not cause accumulation of liver triacylglycerols as LFD, the lipoprotein profile (VLDL, LDL, HDL) was not significantly improved after COD. The consumption of PUFAn-3 was reflected in LDL as an increase in eicosapentaenoic and docosahexaenoic acid. These results suggest that currant oil affects positively the lipid metabolism in the liver, above all it does not cause the development of a fatty liver. However, adverse effects of currant oil on the antioxidant status in the blood still remain of concern.

Administration, Oral↗

Pharmacokinetic study of iodine-labeled silibinins in rat.

The very low bioavailability of silibinin (silybin, SB), the main antioxidant flavonolignan of silymarin from Silybum marianum L. (Asteraceae), requires sensitive methods to study the modulation of silibinin bioavailability. To evaluate the potential for use of radiolabeled silibinin, two silibinin derivatives, separated by HPLC after iodination ((125)I-SB(1) and (125)I-SB(2)) and their complexes 1 : 1 with phosphatidylcholine ((125)I-SPC(1) and (125)I-SPC(2)) were administered concurrently with a single intragastric dose of 5.0 mg or 50 mg of unlabeled silibinin (alone or as a constituent of the complex) per kg of body weight in a comparative study of bioavailability in the rat. Pharmacokinetic parameters as well as organ uptake of (125)I-SB(1)-derived radioactivity showed a dose-response pattern. The parameters of bioavailability after (125)I-SPC(1) intake were not influenced by unlabeled silibinin (complexed with phosphatidylcholine), since maximal levels were achieved by the lower dose of unlabeled compound. The superior bioavailability of (125)I-SPC(1) was obvious at the lower dose of unlabeled compound as elevated AUC and RA(max) (maximal percentage of administered radioactivity), and increased radioactivity in liver, kidney, spleen and heart. An absence of these characteristics with (125)I-SB(2) and (125)I-SPC(2) suggests the use of(125)I-SB(1) for studies of modulation of its bioavailability in vivo in rat.

Animals↗

["Silymarin"--an extract from the milk thistle (Silybum marianum)--is it a drug or nutritional supplement?].

Thanks to the new knowledge, there is an increase of interest in plant extracts in the developed countries, but their classification is, however, problematic. It is necessary to clearly define the borderline between a drug or a defined content of an individual active principle, and a nutritional supplement, which is freely on sale. The extract from the seeds of S. marianum of (ESM) shows biological effects corresponding to nutritional supplements, and it is therefore more logical to class ESM with this group and to investigate the pharmacological effects in its chemically defined components.

Dietary Supplements↗

Activities of silymarin and its flavonolignans upon low density lipoprotein oxidizability in vitro.

Silymarin, a standardized extract from Silybum marianum, inhibited in vitro the copper-induced oxidation of human LDL in a concentration-dependent manner. Silybin, a main flavonolignan of silymarin, appeared to be responsible for this LDL antioxidant effect. Silychristin and silydianin, other flavonolignans of silymarin, acted rather as pro-oxidants, but with regard to their content in silymarin, it did not contribute significantly to the reduction of the total LDL antioxidant capacity of silymarin.

Adult↗

Silymarin inhibits the development of diet-induced hypercholesterolemia in rats.

To study the ability of silymarin, a standardized mixture of antioxidant flavonolignans from the medicinal plant Silybum marianum, and of silybin, the main flavonolignan of silymarin, to inhibit the development of diet-induced hypercholesterolemia the rats were fed high cholesterol diet (HCD). Silymarin or silybin were given as dietary supplements, and their influences on serum cholesterol levels were compared to those of probucol, an antioxidant hypocholesterolemic drug. Anticholesterolemic effect of silymarin was parallel to that of probucol, and dose-dependent at dietary drug concentrations of 0.1-0.5-1.0% (w/w). However, in contradistinction to probucol, silymarin caused an increase in high density lipoprotein (HDL)-cholesterol and a decrease in liver cholesterol content, changes considered to be of benefit. In addition to its anticholesterolemic effect silymarin partially prevented the HCD-induced decrease in liver reduced glutathione, an endogenous antioxidant. Silybin was not so effective as silymarin suggesting that either other constituent(s) of silymarin may be responsible for its anticholesterolemic effect or the bioavailability of silybin alone might be lower than that of silybin as a compound of silymarin.

Animals↗

Dietary silymarin improves removal of low density lipoproteins by the perfused rat liver.

Silymarin administered to the rats concurrently with high cholesterol diet normalized the high cholesterol diet-induced retardation of disappearance of low density lipoproteins (LDL) from the medium during recirculating perfusion of livers from these rats. We suggest that the improvement of LDL removal by the liver after silymarin treatment contributes to the antihypercholesterolemic effect of silymarin.

Animals↗

Effect of silymarin on serum cholesterol levels in rats.

Previously we have shown that perorally administered silymarin, a mixture of flavonolignans extracted from the seeds of Silybum marianum, possesses a hypocholesterolemic effect in rats fed high cholesterol diet enriched with fat. The aim of this paper was to complete the data concerning peroral and parenteral administration of silymarin. The rats fed standard laboratory diet did not respond to peroral administration of silymarin by decrease of serum cholesterol, but the mild increase in HDL cholesterol was found. Parenterally injected silymarin failed to reduce serum cholesterol both in rats fed high cholesterol diet and standard laboratory diet. The results suggest that silymarin could act either due to the fat-mediated improved bioavailability and/or by inhibiting of resorption of dietary cholesterol.

Administration, Oral↗

Silymarin as a potential hypocholesterolaemic drug.

Silymarin, a mixture of flavonolignans from medicinal plant Silybum marianum, is used in supportive treatment of liver diseases of different etiology due to its hepatoprotective activity, which is considered to involve antioxidative and the membrane stabilizing effects. The liver plays an important role in regulation of metabolism of plasma lipoproteins, and liver injury is often reflected as a secondary dyslipoproteinaemia, which may lead to the development of atherosclerosis, particularly when associated with hypercholesterolaemia. This review summarizes the experimental evidence indicating that silymarin-induced protection of liver functions may be of benefit with regard to liver lipid metabolism related to the regulation of plasma lipoproteins. Moreover, some data suggest that silymarin could have a direct effect on liver cholesterol metabolism by inhibiting cholesterol biosynthesis. It is proposed that silymarin deserves to be studied as a potential hypocholesterolaemic agent.

Animals↗

[Use of etofyllinclofibrate (Duolip Forte) in combined hyperlipidemia].

BACKGROUND: Duolip forte (ethophyllinclofibrate) is a lipid lowering drug, the effect of which was not yet adequately verified in our conditions, namely from the point of its effect on various types of hyperlipoproteinaemias. METHOD AND RESULTS: The therapy was applied on 45 patients with combined hyperlipidaemia, 25 men and 20 women, mean age 53.8 years (age range 41-65). About one half of patients were treated for hypertension, almost one quart of them manifested ischemic heart disease, 13% had a history of myocardial infarction and the same percentage suffered from associated diabetes type 2. Duolip forte was administered perorally in a dose of 500 mg once daily for 12-16 weeks to the patients who had complied with the prescribed diet (weight loss, improvement of lipid levels) during three-month preliminary period, but did not reach desirable parameters. After the therapy, the whole group studied manifested a significant decrease of total cholesterol (-10.8%), LDL-cholesterol (-13%), triglycerides (-40.8%) and free fatty acids (-20.6%), while the increase of HDL-cholesterol and its fractions was not significant. In hyperlipoproteinaemias of IIa type (n = 15), only a significant decrease of LDL-cholesterol appeared, in hyperlipoproteinaemias of IIb type (n = 15), a significant decrease was evidenced only in triglycerides (-33.9%). In hyperlipoproteineaemias of IV type (n = 15), a significant decrease was observed in triglycerides (-50.3%), while HDL-2 cholesterol values increased (+32.3%). A slight decrease of uric acid level and of body mass index observed in all groups was statistically not significant, as well as a slight increase of glycaemia and changes of serum transaminases. No unwanted side effects of Duolip were found. CONCLUSIONS: Ethophyllinclofibrate has proved as effective namely at hypertriglyceridemic primary hyperlipidaemias. Besides decreasing triglycerides, it increases significantly HDL-2 cholesterol. A convenient dosage, small lithogenic effect and minimum of side effects make it a drug of choice for some groups of elderly high-risk patients.

Adult↗

Serum lipoprotein fatty acid patterns in various types of familiar combined hyperlipidemia.

The relative content of various fatty acids in serum lipoproteins was determined in patients with type IIa (38), IIb (49) and IV (77) of hyperlipoproteinemia and compared with 52 controls. Significant changes were found in hyperlipoproteinemia associated with hypertriglyceridemia (type IV) but not in "pure" hypercholesterolemia (type IIa). In all lipoprotein fractions (VLDL, LDL, HDL) in type IV of hyperlipoproteinemia the increased oleic and linolenic acid proportions were found, while proportions of linoleic, arachidonic and docosahexaenoic acids were decreased. The saturated fatty acids (myristic, palmitic and stearic) were found increased in LDL. Linear regression analysis has shown positive correlation between the content of arachidonic and docosahexaenoic acids in HDL and LDL and the serum levels of total HDL-cholesterol, HDL2-cholesterol, HDL3-cholesterol and ApoA1, while a negative correlation between these fatty acids and serum triglycerides level appeared. These findings can be explained partly by increased content of triglycerides and free fatty acids in lipoproteins. Possible differences concerning mechanisms of accelaration of atherogenesis in various types of hyperlipidemia are discussed.

Fatty Acids↗

Unsaturated fatty acids incorporated in HDL in hypo- and hyperalphalipoproteinemia--relation to the HDL-cholesterol level.

Proportions of unsaturated fatty acids of high density lipoprotein (HDL) lipids and their relationships to the HDL-cholesterol level were compared in hypo- and hyperalphalipoproteinemic subjects. Both groups did not differ in the level of serum cholesterol. However, hypoalphalipoproteinemia was associated with hypertriglyceridemia, higher HDL-triacylglycerol level, and higher proportion of HDL-18:1 (oleic acid) and lower proportions of HDL-18:2 (linoleic acid) and 20:4 (arachidonic acid) than hyperalphalipoproteinemia. The HDL-20:4 was the only fatty acid correlating (negatively) with HDL-cholesterol. However, HDL-18:1 correlated positively and HDL-18:2 negatively with HDL-triacylglycerols, lipids related to the fall of HDL-cholesterol. These results suggest 1) an antagonism of 20:4 and 18:2 as structural components of HDL lipids in relation to the HDL-cholesterol level, and 2) an association of replacement of HDL 18:2 by 18:1 with the disorder of plasma triacylglycerol metabolism.

Cholesterol, HDL↗

The preheparin and postheparin lipids of high density lipoprotein subfractions: relation to the serum insulin and postheparin plasma lipase activities in normal human.

The preheparin and postheparin lipoprotein lipids (cholesterol C and triacylglycerols TAG) were related to the serum insulin and to the postheparin plasma activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in normolipemic human. The positive correlation, although not statistically significant, of insulin level of the LPL activity was found, while no correlation to the HL activity was seen. Under preheparin conditions: 1) both insulin level and LPL activity were negatively related to the VLDL-C/TAG ratio indicating an enrichment of VLDL with TAG, 2) moreover, the LPL activity was positively related to the HDL-C and HDL3-C, 3) the HL activity predominated in relation to the HDL, and particularly to the HDL3, as indicated by negative correlations to the both lipids and to the lipid/apoA-I ratios of HDL and HDL3. This lipid depletion of HDL3 was more expressive due to the TAG, while HDL2 appeared to be relatively enriched with TAG, as suggested by correlations of C/TAG ratios with HL activity. The in vivo acceleration of lipoprotein metabolism by heparin resulted in: 1) the reduction of VLDL-TAG and HDL2-TAG, and in the increase of HDL3-TAG, 2) the appearance of positive relation of HDL2-C to the LPL activity and of opposite relation to the HL activity, 3) the lack of HL correlation to the TAG of HDL and HDL3. Even under these conditions no relation of insulin level to any HDL lipid was revealed. The results suggest that in normal human the HL affects more considerably than LPL the lipid metabolism of HDL subfractions and it does not seem to be under insulin control.

Adult↗

The effect of N-deacetylcolchiceine on serum lipoproteins in rats.

N-Deacetylcolchiceine (DAC) administered i.p. to rats decreased the level of serum cholesterol and apoB. It was accompanied by the fall of HDL-C due to the decrease of both HDL subfractions HDLa and HDLb, and by a rather weaker decrease of LDL-C. The levels of serum and lipoprotein triacylglycerols were not significantly affected. The "clearing reaction" to heparin in DAC rats differed from controls with regard to plasma cholesterol resulting in its accumulation in HDLa and LDL simultaneously with an increased activity of post-heparin lipoprotein lipase. These results suggest that the DAC accelerates the lipoprotein cholesterol metabolism.

Animals↗

[Personal experience with lovastatin, a HMG-CoA reductase inhibitor (Mevacor, MSD) in the treatment of hypercholesterolemia].

The authors administered lovastatin (Mevacor, MSD) to 18 patients with primary hyperlipoproteinaemia (familial and non-familial) with a lipoprotein pattern type IIa and IIb. During treatment a marked reduction of atherogenic indicators of the lipid metabolism occurred, i.e. a decline of total cholesterol (-28.6%), LDL-cholesterol -39%), apolipoprotein B (-18.6%), the index of total cholesterol/HDL-cholesterol (-44.6%) and the index LDL-cholesterol/HDL-cholesterol (-48.2%). At the same time a favourable effect on indicators of the lipid metabolism to which a protective action is ascribed was recorded: a rise of HDL-cholesterol (+13.6%) and apolipoprotein AI (+13%) and AII (+13%). An excellent effect was observed also in four heterozygotes with familial hypercholesterolaemia which is usually rather resistant to other types of hypolipidaemic treatment. The drug was very well tolerated and subjective side-effects of treatment were minimal. Despite the fact that a number of laboratory indicators was followed up, the authors did not observe any undesirable side-effects, only a transient and marginal rise of ALT in one patient. Lovastatin is, due to its potent hypolipidaemic effect, a new hope in the treatment of hypercholesterolaemia. Its usefulness in the prevention of ischaemic heart disease, as well as its safety during prolonged administration are tested at present in long-term investigations.

Female↗

High-density lipoprotein subpopulations as substrates for the transfer of cholesteryl esters to very-low-density lipoproteins.

1. Human total HDL (high-density lipoprotein), HDL2 and HDL3 were labelled in vitro by incubation with lipoprotein-deficient serum (LPDS) which contained either [3H]cholesteryl oleate or [14C]cholesterol under different conditions. The lipoproteins were then subfractionated by heparin-Sepharose column chromatography, and three subfractions (A, B and C) were successively eluted from each preparation of HDL, HDL2 and HDL3. When the labelling was done at 37 degrees C for 17 h, the subfractions were homogeneously labelled with [3H]cholesteryl oleate. However, when it was performed for only 30 min at 4 degrees C, the subfractions showed marked differences in the 3H specific radioactivity, which was much higher in the C fractions than in the others. 2. 3H-labelled HDL2 and HDL3 subfractions behaved differently under the precipitant action of heparin-Mn2+; fraction C (the richest in apolipoprotein E) produced the largest amount of radioactive and chemical precipitate. More 3H radioactivity, but not the cholesterol, was precipitated from HDL2 or HDL3 by the reagent, demonstrating that 3H-labelled HDL2 and HDL3 behave like their fraction C, which becomes labelled to the highest specific radioactivity despite having the smallest mass. 3. The incubation of 3H-labelled HDL subfractions with human LPDS and very-low-density lipoprotein (VLDL) at 37 degrees C increased the quantity of 3H radioactivity that was precipitated, in proportion to the amount of VLDL present in the media. These changes were attributable to the action of cholesterol ester transfer protein, since they did not occur at 4 degrees C or when human LPDS was replaced with rat LPDS. 4. Kinetics of the transfer of HDL [3H]cholesteryl oleate to VLDL showed a greater apparent Vmax for fractions A than for fractions B from either HDL2 or HDL3, whereas the apparent Km values were very similar, which suggest that this transfer process is influenced by the apoprotein composition of the donor lipoprotein.

Animals↗

Effect of manganese ions on HDL2 precipitation with dextran sulfate.

The dual precipitation method involving the separation of HDL and HDL3 from normolipemic serum by heparin-MnCl2/dextran sulfate was evaluated with regard to the Mn2+ effect on HDL2 precipitation with dextran sulfate (DS) in the second precipitation step. Increased HDL2-C and HDL2-TAG values brought about by increased Mn2+ concentrations were found at all DS concentrations studied. The comparison of the lipid HDL2 and HDL3 values with those given by polyethylene glycol precipitation method yielded two optimal combinations of DS/Mn2+ concentrations: 1.11 g.l-1/0.076 mol.l-1 and 0.87 g.l-1/0.091 mol.l-1. The obtained results call attention to the importance of final concentration of Mn2+ ions at HDL2 precipitation with DS from heparin-Mn2+ supernate containing HDL.

Adult↗

Activity of lipoprotein lipase in thyroidectomized rats.

Total plasma postheparin lipolytic activity as well as lipoprotein lipase activity in plasma was higher after heparin injection in thyroidectomized rats than in controls. In contrast, the activity of liver lipase was lower in thyroidectomized rats. Adipose tissue from thyroidectomized rats contained more lipoprotein lipase activity than adipose tissue from controls as measured both in extracts of tissue homogenates and medium from in vitro incubations of tissue pieces. There were no differences between control and hypothyroid rats in the disappearance of intravenously injected 125I-labeled lipoprotein lipase, but when a low dose of heparin was injected before the labeled enzyme, the disappearance of 125I-labeled lipoprotein lipase was more retarded in thyroidectomized rats. The elimination of heparin itself was slightly retarded by thyroidectomy.

Adipose Tissue↗

The influence of thyroxine on the plasma post-heparin lipolytic activity in rats.

10 min after heparin administration (25 IU per 100 g body weight) the plasma post-heparin lipolytic activity (PHLA) was increased in thyreoidectomized (TECT), hypophysectomized (HX) and hypophysectomized + thyreoidectomized (HX + TECT) rats to the same extent as in intact and sham hypophysectomized controls. However, 60 min after heparin the increase of PHLA persisted only in the TECT, HX and HX + TECT rats. After an administration of thyroxine to TECT rats (25 microgram per 100 g body weight) and also to HX + TECT rats (25 microgram or 100 microgram per 100 g body weight) the PHLA decreased similarly as in controls 60 min after heparin administration. The results suggest that the increased PHLA in hypothyroid rats is caused by the deficiency of thyroid hormones, while TSH released after TECT seems not involved in the regulation of enzymes degrading plasma lipoproteins.

Animals↗