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Biomedical subjects

F Visioli

Publications and source records attributed to F Visioli.

54 records · Page 3Linked to original sources

Antioxidant and other biological activities of olive mill waste waters.

During olive oil production, large volumes of water are generated and subsequently discarded. Olives contain a variety of bioactive components, and some of them, according to their partition coefficients, end up in the water phase. The current investigation aimed at comparing different methods for the extraction of biologically active components of the olive mill waste waters (OMWW) and evaluating the in vitro antioxidant and anti-inflammatory activities of the resulting extracts. The results indicate that OMWW extracts are able to inhibit human LDL oxidation (a process involved in the pathogenesis of atherosclerosis) and to scavenge superoxide anions and hypochlorous acid at concentrations as low as 20 ppm. Finally, two of the three extracts also inhibited the production of leukotrienes by human neutrophils. The potency of the extracts depended on their degree of refinement: extracts containing only low molecular weight phenols were the most effective.

Antioxidants↗

Free radical-scavenging properties of olive oil polyphenols.

Plants in the Mediterranean basin, such as vine and olive trees, have developed an array of antioxidant defences to protect themselves from environmental stress. Accordingly, the incidence of coronary heart disease and certain cancers is lower in the Mediterranean area, where olive oil is the dietary fat of choice. As opposed to other vegetable oils, extra virgin olive oil, which is obtained by physical pressure from a whole fruit, is rich in phenolic components that are responsible for the particular stability of the oil. We have investigated the scavenging actions of some olive oil phenolics, namely hydroxytyrosol and oleuropein, with respect to superoxide anion generation, neutrophils respiratory burst, and hypochlorous acid. The low EC50S indicate that both compounds are potent scavengers of superoxide radicals and inhibitors of neutrophils respiratory burst: whenever demonstrated in vivo, these properties may partially explain the observed lower incidence of CHD and cancer associated with the Mediterranean diet.

Antioxidants↗

Oxidation of individual fatty acids yields different profiles of oxidation markers.

Free radicals attack lipid molecules and initiate a chain of reactions that may trigger several diseases such as atherosclerosis and cancer. Several markers of oxidative stress have been proposed, including measurements of lipid peroxides and short-chain aldehydes levels and evaluation of conjugated diene formation. Although it is generally assumed that fatty acid oxidizability is directly proportional to their degree of unsaturation, little is known about the contribution of individual fatty acids to each of these markers. We investigated such contributions in a model of AAPH-mediated peroxidation of individual fatty acid micelles by assessing several indices of oxidative stress. The results suggest that the generation of oxidation products by individual fatty acids is not directly related to their degree of unsaturation and indicate that the differential contribution of individual fatty acids should be taken into account and more than one marker of lipid peroxidation should be included in in vivo studies of oxidative stress.

Amidines↗

S-adenosyl-L-methionine: role in phosphatidylcholine synthesis and in vitro effects on the ethanol-induced alterations of lipid metabolism.

Hepatic lipid metabolism is extremely modified by excessive ethanol consumption, but the cellular mechanisms of such alterations are still largely unexplored. S-Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a precursor of glutathione and it has been shown to prevent some of the toxic effects of ethanol in the liver. We therefore studied the effects of ethanol on cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of SAMe, and its putative protective effects on the alterations of lipid metabolism induced by toxic concentrations of alcohol. Incubation of HepG2 cells with [3H]SAMe resulted in a progressive increase in the labelling of phosphatidylcholine and of its two intermediates during synthesis starting from phosphatidylethanolamine. This process is enzymatic, since it does not take place in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and triglycerides syntheses and a decrease in phospholipid labelling. These alterations were not prevented by SAMe 10(-4) M, indicating that the protective effects of the drug are related to other mechanisms of action such as reduced formation of collagen, restoration of glutathione levels, and normalization of membrane functions.

Acetates↗

Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages.

The Mediterranean diet, rich in fresh fruits and vegetables, has been associated with a lower incidence of cardiovascular disease and cancer, partly because of its high proportion of bioactive compounds such as vitamins, flavonoids and polyphenols. The major lipid component of such diet is the drupe-derived olive oil, that can be distinguished from other seed oils for the peculiar composition of its non-triglyceride fraction. In fact, several minor components, including polyphenols, grant the oil its particular taste and aroma. Oleuropein, the most abundant among these components, has been shown to be a potent antioxidant endowed with antiinflammatory properties. We investigated the effects of oleuropein on NO release in cell culture and its activity toward nitric oxide synthase (iNOS) expression. The results show that oleuropein dose-dependently enhance nitrite production in LPS-challenged mouse macrophages. This effect was blocked by the iNOS inhibitor L-NAME, indicating increased iNOS activity. Also, Western blot analysis of cell homogenates show that oleuropein increases iNOS expression in such cells. Taken together, our data suggest that, during endotoxin challenge, oleuropein potentiates the macrophage-mediated response, resulting in higher NO production, currently believed to be beneficial for cellular and organismal protection.

Animals↗

Ethanol enhances cholesterol synthesis and secretion in human hepatomal cells.

Excessive consumption of alcohol leads to severe alterations of lipid metabolism, including hyperlipemia and hypercholesterolemia. Following these epidemiological observations, we investigated the effects of ethanol at the cellular level by employing a human hepatomal cell line (HepG2) and by evaluating the biosyntheses of lipid classes from different labeled precursors. Incubation of cells with 2% ethanol resulted in a decreased labeling of phospholipids and in an increase in cholesterol synthesis and secretion. Triglyceride synthesis was increased by ethanol but their secretion in the medium was reduced, suggesting that these alterations may be related to their accumulation in the liver. The alcohol-induced alterations of lipid metabolism are not due to its metabolite acetaldehyde and data suggest that alcohol enhances cholesterol synthesis by affecting the initial steps without increasing HMGCoA expression. The observed modifications of lipid metabolism in HepG2 may partially explain the enhanced incidence of cardiovascular disorders that has been associated with alcoholism.

Acetates↗

The effect of minor constituents of olive oil on cardiovascular disease: new findings.

There has been much interest regarding the components that contribute to the beneficial health effects of the Mediterranean diet. Recent findings suggest that polyphenolic compounds found in olive oil are endowed with several biologic activities that may contribute to the lower incidence of coronary heart disease in the Mediterranean area.

Cardiovascular Diseases↗

Manipulation of the fate of long chain polyunsaturated fatty acids in cultured cells.

We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) from their precursors in cultured cells undergoing physiological modifications, or under the influence of lipid-lowering drugs or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of differentiation, and declines when differentiation is complete, in concomitance with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase inhibitor simvastatin (S), an effect which is reverted by mevalonate and other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those required for maximal inhibition of cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potentiating the incorporation of acetate into cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell differentiation and complex interactions between LC-PUFA and cholesterol synthesis occur, as judged from data obtained through pharmacological manipulations.

Arachidonic Acid↗

'Waste waters' from olive oil production are rich in natural antioxidants.

Milling of olive paste during olive oil production is accompanied by continuous washing with water, i.e. malaxation. The resulting 'waste-water' is currently discarded. Since olives and olive oil are rich in natural antioxidants, we hypothesized that some of these might be extracted from the olive paste during malaxation. Interest in natural antioxidants is increasing because of the growing body of evidence indicating the involvement of oxygen-derived free radicals in several pathological processes, such as cancer and atherosclerosis. A waste-water extract was characterized by HPLC and tested in a model of lipid peroxidation, copper sulphate-induced oxidation of low density lipoproteins. The results demonstrate that waste-water extracts have powerful antioxidant activity and might therefore represent a cheap, as yet unused, source of natural antioxidants.

Antioxidants↗

Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents.

Oxidation of low density lipoproteins maybe a factor in the development of atherosclerosis. The Mediterranean diet rich in vegetables, grains, legumes, fruits, and oils, mainly olive oil, has been suggested to reduce the incidence of coronary heart disease, because of its low saturated and high monounsaturated fatty acids content. It is also possible that the natural antioxidants in the oil help to prevent lipid oxidation, e.g. that of low density lipoproteins, thus retarding the formation of atherosclerotic plaques. First-pressed, extra-virgin olive oil contains appreciable amounts of polyphenolic compounds that prevent its autoxidation and are responsible for its high stability. We tested these compounds on low density lipoprotein oxidation and found an inhibitory effect, at low concentrations, on various indexes of lipid oxidation (vitamin E content, formation of thiobarbituric acid-reacting substances, lipid peroxides, levels of polyunsaturated fatty acids, protein modification, conjugated diene formation). Our data suggest that natural antioxidants could play a role in inhibiting the formation of cytotoxic products such as lipid peroxides thus retarding the onset of the atherosclerotic damage.

Arteriosclerosis↗

Formation of F2-isoprostanes in oxidized low density lipoprotein: inhibitory effect of hydroxytyrosol.

Oxidatively-modified low-density lipoproteins (LDL) contribute to the onset of the atherosclerotic disease. A recently discovered marker of lipid peroxidation in a series of prostaglandin F2-like compounds, the prostaglandin isomers isoprostanes, that are generated from arachidonic acid through cyclooxygenase-independent pathways following free radical injury and are endowed with potent biological activities. The incidence of cardiovascular disease in the Mediterranean area is low, possibly because of the type of fat (mainly olive oil) and other components (e.g. fruits and vegetables) of the diet. Natural antioxidants abound in this kind of diet and may also contribute to the observed protection from coronary heart disease (CHD) by retarding the formation of the atherosclerotic plaque. Olive oil, the major dietary fat in the Mediterranean countries, is rich in phenols with antioxidant properties. We thus investigated the formation of isoprostanes during in vitro LDL oxidation and tested the effect of an olive-oil-extracted phenol (i.e. hydroxytyrosol). Our data show that production of isoprostanes and other markers of lipid peroxidation occurs during LDL oxidation and is inhibited by hydroxytyrosol.

Antioxidants↗

Daily electroconvulsive shock treatment alters the inositol lipid system response in the rat hippocampus.

The inositol lipid system (polyphosphoinositides and inositol phosphates) represents an important component of the cell signal transduction. Electroconvulsive shock (ECS) is known to activate cell signaling and lead to the release of second messengers. We tested the effects of daily ECS on the inositol lipid system and the generation of second messengers in vivo, by prelabeling the components of the system with [3H]myo inositol. The response to ECS was greater 30 sec after the sixth ECS, as compared to that obtained 30 sec after the first one. Also, rats killed 24h after the fifth ECS exhibited an increased PI labeling, as compared to rats handled for 6 days without receiving ECS. These results show that daily seizures (ECS-evoked) deeply modify the neuronal response to the stimulus, thus providing new information on the biochemical events involved in cell signal transduction during seizures.

Animals↗

Membrane lipid degradation is related to interictal cortical activity in a series of seizures.

Brain levels of free fatty acids (FFA) and diacylglycerols (DAG) rise rapidly with the onset of seizures, reflecting activation of phospholipases A2 (PLA2) and C (PLC), respectively. However, the ictal/interictal accumulation of FFA attenuates as recurrent seizures continue. To assess the role of neuronal activity in stimulating PLA2 and C, we compared FFA and DAG in rat cerebral cortex during recurrent ictal periods as a function of associated levels of interictal activity. Pentobarbital-anesthetized rats were paralyzed, ventilated with 30% O2 and subjected to periodic pentylenetetrazol seizures at intervals of 5 min. Animals were killed with focused-microwave irradiation during either the 3rd or 15th seizure. The rise in cortical FFA levels during early seizures for 20:4, 22:6, and 18:0 was 3.6-, 2.5-, and 2.2-fold greater, respectively, when adjacent interictal activity was intense as compared to weak activity. During late seizures, this difference dropped to 2.2-fold for 20:4, the only FFA that showed a significantly higher value between robust versus weak interictal activity. In contrast, accumulation of DAG during early and late seizures was observed only when adjacent interictal activity was high. These results indicate that the cortical accumulation of FFA and DAG during ictal periods of similar intensity and duration depends upon the electrocortical activity during adjacent interictal periods.

Animals↗

Oleuropein protects low density lipoprotein from oxidation.

The Mediterranean diet, rich in fruit, vegetables, grain, and vegetable oil (mainly olive oil) is correlated with a lower incidence of coronary heart disease (CHD). Natural antioxidants contained in the Mediterranean diet might also play a role in the prevention of cardiovascular diseases, through inhibition of LDL oxidation. We tested this hypothesis "in vitro" by inducing LDL oxidation with copper sulphate and preincubating the samples with oleuropein, the bitter principle of olives, that is one of the major components of the polyphenolic fraction of olive oil. Oleuropein 10(-5) M effectively inhibited CuSO4-induced LDL oxidation, as assessed by various parameters. We demonstrate in this investigation that polyphenolic components of the Mediterranean diet interfere with biochemical events that are implicated in atherogenetic disease, thus proposing a new link between the Mediterranean diet and prevention of CHD.

Antioxidants↗

Free fatty acid and diacylglycerol accumulation in the rat brain during recurrent seizures is related to cortical oxygenation.

Cerebral blood flow and oxygenation increase during the early seizures of a series, but the increase in cerebral blood flow attenuates during late seizures, sometimes resulting in decreased cortical oxygenation. Cortical free fatty acids (FFA) and diacylglycerols also increase during early seizures and the increase attenuates during late seizures. We analyzed the correlation between lipid accumulation and cortical O2 during periodic pentylenetetrazol-induced seizures. During early seizures, both FFA and diacylglycerols increased in the cerebral cortex, particularly arachidonate (20:4) and stearate (18:0). Changes in lipids were different during late seizures, depending on cortical O2 levels. An increase in cortical O2 during late seizures was associated with lower FFA levels compared with early seizures, and FFA levels recovered to basal levels during interictal periods. A decline in cortical O2 was associated with a further increase in FFA, which remained elevated during interictal periods. Our results indicate that periseizure lipid accumulation is related to cortical oxygenation.

Animals↗

Arachidonic acid cycloxygenase and lipoxygenase pathways are differently activated by platelet activating factor and the calcium-ionophore A23187 in a primary culture of astroglial cells.

The aim of our study has been to investigate the metabolism of endogenous arachidonic acid or that of radiolabeled arachidonate in astroglial cells, stimulated with platelet activating factor (PAF) and with the calcium-ionphore A23187. Primary cultures of astroglial cells were obtained from brain cortex of one-day-old rats and were characterized by immunofluorescent staining vs glial fibrillary acidic protein. In labeled cells, diacylglycerol was formed after stimulation with platelet activating factor, whereas mainly the release of labeled arachidonic acid from phospholipids was observed after stimulation with calcium-ionophore. Both PAF and the calcium-ionophore A23187 actively stimulated the formation of the cycloxygenase products PGD2, TXB2 and 6-keto-PGF1 alpha, measured by radio- or enzyme-immunoassay. Differences were observed, instead, in the formation of the lipoxygenase metabolites, the hydroxyeicosateraenoic acids, which were measured by high pressure liquid chromatography (HPLC) with on line radiodetection for the labeled products, and Leukotriene C4, measured by radioimmunoassay. The formation of hydroxyacids by stimulated cells was confirmed by gas chromatography-mass spectrometry (GC-MS). In labeled cells, both agonists induced the formation of 12- and 15-hydroxyeicosatetraenoic acids, whereas stimulation of unlabeled cells with calcium ionophore resulted in formation of 12-hydroxyeicosatetraenoic acid and Leukotriene C4. Our results suggest that in astroglial cells, PAF, a compound which is produced in several tissues including brain, mobilizes a selected arachidonic acid pool, possibly associated with diacylglycerol production, from phospholipids, thus activating the conversion of the released fatty acid via the cyclo and the 12-lipoxygenase pathways.

Animals↗