Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
2.
J Agric Food Chem ; 53(24): 9602-7, 2005 Nov 30.
Article in English | MEDLINE | ID: mdl-16302783

ABSTRACT

Chemically stable di- and triacetyl derivatives of the natural o-diphenol antioxidant hydroxytyrosol were synthesized, and their chemical and biological antioxidant activities were assessed in comparison with that of the native synthetic compound. The chemical antioxidant activity of the selected compounds was evaluated by measuring the ferric reducing antioxidant power (FRAP). The data clearly indicate that, as expected, the hydroxytyrosol analogues, modified in the o-diphenolic ring, are devoid of any chemical antioxidant activity. On the contrary, both acetyl derivatives, at micromolar concentrations, equally protect against tert-butylhydroperoxide-induced oxidative damages in Caco-2 cells and human erythrocytes. This paper for the first time reports that chemically stable hydroxytyrosol acetyl derivatives, although devoid of chemical antioxidant activity, are as effective as the parent compound in protecting human cells from oxidative stress-induced cytotoxicity, after metabolization by esterases at the intestinal level, suggesting their possible utilization in either nutritional (functional food), cosmetic, or pharmaceutical preparations.


Subject(s)
Antioxidants/pharmacology , Oxidative Stress/drug effects , Phenylethyl Alcohol/analogs & derivatives , Acetylation , Erythrocytes/drug effects , Humans , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/pharmacology
3.
Nephrol Dial Transplant ; 20(8): 1551-8, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15855205

ABSTRACT

BACKGROUND: As is well known, the use of the immunosuppressive drug cyclosporin A (CsA) is partially restricted by its nephrotoxic effects, which include early changes in haemodynamics followed by irreversible injuries to the renal tubules. Although the mechanisms responsible for these side effects are poorly understood, an involvement of reactive oxygen species (ROS) has been suggested. In this study, we selected three natural antioxidants, resveratrol, hydroxytyrosol and vitamin E, on the basis of their scavenging capabilities, and tested their protective effects against CsA toxicity. METHODS: Immortalized rat tubular cells (RPTc) were used as the model system. Cell viability was checked with trypan blue assay, and free radical formation was measured using the fluorescent probe 2,7-dichlorofluorescein (DCF). We evaluated several oxidative stress parameters, including phospholipid peroxidation products, glutathione levels and oxygenase expression. RESULTS: Incubation of RPTc with 25 muM CsA induced a significant decrease in cell viability paralleled by intracellular ROS formation and alterations in lipid peroxidation. There was also an imbalance of glutathione redox state as well as upregulation of heme oxygenase-1 (HO-1). The three antioxidants, at micromolar concentration, quantitatively prevented the ROS-activated DCF fluorescent signal and membrane lipid peroxidation. Both hydroxytyrosol and resveratrol strengthened the CsA induction of HO-1 expression. Moreover, vitamin E and resveratrol counteracted CsA-induced changes in the glutathione redox state via different mechanisms, whereas hydroxytyrosol was completely ineffective. Similarly, CsA-dependent nephrotoxicity was prevented by vitamin E, while resveratrol only exerted partial protection, and hydroxytyrosol showed no protective effects. CONCLUSION: Our results indicate that the diverse cytoprotective effects of the antioxidants tested in these studies were not directly related to their scavenging capabilities. These findings confirm a key role for glutathione in protecting cells from CsA-induced adverse effects and do not support a direct link between CsA-mediated ROS generation and adverse renal effects.


Subject(s)
Antioxidants/therapeutic use , Cyclosporine/toxicity , Kidney Diseases/prevention & control , Kidney Tubules, Proximal/drug effects , Phenylethyl Alcohol/analogs & derivatives , Stilbenes/therapeutic use , Vitamin E/therapeutic use , Animals , Cell Survival/drug effects , Cells, Cultured , Epithelium/drug effects , Fluoresceins , Glutathione/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Kidney Tubules, Proximal/metabolism , Lipid Peroxides/metabolism , Phenylethyl Alcohol/therapeutic use , Rats , Rats, Inbred WKY , Reactive Oxygen Species/metabolism , Resveratrol , Thiobarbituric Acid Reactive Substances/metabolism
4.
Free Radic Biol Med ; 38(7): 908-19, 2005 Apr 01.
Article in English | MEDLINE | ID: mdl-15749387

ABSTRACT

Previous studies showed that long-wave ultraviolet (UVA) radiation induces severe skin damage through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. Recent results from our laboratory indicate a dramatic increase of both lipid peroxidation products (TBARS) and abnormal L-isoaspartyl residues, marker of protein damage, in UVA-irradiated human melanoma cells. In this study, the effects of hydroxytyrosol (DOPET), the major antioxidant compound present in olive oil, on UVA-induced cell damages, have been investigated, using a human melanoma cell line (M14) as a model system. In UVA-irradiated M14 cells, a protective effect of DOPET in preventing the uprise of typical markers of oxidative stress, such as TBARS and 2'7'-dichlorofluorescein (DCF) fluorescence intensity, was observed. In addition, DOPET prevents the increase of altered L-isoAsp residues induced by UVA irradiation. These protective effects are dose dependent, reaching the maximum at 400 microM DOPET. At higher concentrations, DOPET causes an arrest of M14 cell proliferation and acts as a proapoptotic stimulus by activating caspase-3 activity. In the investigated model system, DOPET is quantitatively converted into its methylated derivative, endowed with a radical scavenging ability comparable to that of its parent compound. These findings are in line with the hypothesis that the oxidative stress plays a major role in mediating the UVA-induced protein damage. Results suggest that DOPET may exerts differential effects on melanoma cells according to the dose employed and this must always be taken into account when olive oil-derived large consumer products, including cosmetics and functional foods, are employed.


Subject(s)
Antioxidants/pharmacology , Melanoma/metabolism , Oxidative Stress/drug effects , Phenylethyl Alcohol/analogs & derivatives , Proteins/radiation effects , Ultraviolet Rays , Antioxidants/metabolism , Apoptosis , Humans , Isoaspartic Acid/analysis , Lipid Peroxidation/drug effects , Methylation/drug effects , Olive Oil , Oxidation-Reduction , Phenylethyl Alcohol/metabolism , Phenylethyl Alcohol/pharmacology , Plant Oils/chemistry , Proteins/chemistry , Proteins/metabolism , Reactive Oxygen Species/metabolism , Thiobarbituric Acid Reactive Substances/analysis , Tumor Cells, Cultured
5.
J Nutr Biochem ; 15(8): 461-6, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15302080

ABSTRACT

The potential protective effects of oleuropein, a dietary antioxidant of olive oil, has been investigated in the isolated rat heart. The organs were subjected to 30 minutes of no-flow global ischemia and then reperfused. At different time intervals, the coronary effluent was collected and assayed for creatine kinase activity as well as for reduced and oxidized glutathione. In addition, the extent of lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substance concentration in cardiac muscle. Pretreatment with 20 microg/g oleuropein before ischemia resulted in a significant decrease in creatine kinase and reduced glutathione release in the perfusate. The protective effect of oleuropein against the post-ischemic oxidative burst was investigated by measuring the release, in the coronary effluent, of oxidized glutathione, a sensitive marker of heart's exposure to oxidative stress. Reflow in ischemic hearts was accompanied by a prompt release of oxidized glutathione; in ischemic hearts pretreated with oleuropein, this release was significantly reduced. Membrane lipid peroxidation was also prevented by oleuropein. The reported data provide the first experimental evidence of a direct cardioprotective effect of oleuropein in the acute events that follow coronary occlusion, likely because of its antioxidant properties. This finding strengthens the hypothesis that the nutritional benefit of olive oil in the prevention of coronary heart disease can be also related to the high content of oleuropein and its derivatives. Moreover, our data, together with the well documented antithrombotic and antiatherogenic activity of olive oil polyphenols, indicate these antioxidants as possible therapeutic tools for the pharmacological treatment of coronary heart disease as well as in the case of cardiac surgery, including transplantation.


Subject(s)
Myocardial Ischemia/prevention & control , Myocardial Reperfusion Injury/prevention & control , Pyrans/pharmacology , Animals , Creatine Kinase/drug effects , Creatine Kinase/metabolism , Glutathione/metabolism , In Vitro Techniques , Iridoid Glucosides , Iridoids , Lipid Peroxidation/drug effects , Male , Myocardial Ischemia/metabolism , Myocardial Ischemia/pathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardium/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Thiobarbituric Acid Reactive Substances/metabolism
6.
J Agric Food Chem ; 50(22): 6521-6, 2002 Oct 23.
Article in English | MEDLINE | ID: mdl-12381144

ABSTRACT

This paper reports the protective effect of the phenolic fraction extracted from extra virgin olive oils (OOPEs) against the cytotoxic effects of reactive oxygen species in human erythrocytes and Caco-2 cells, employed as model systems. Pretreatment of cells with various OOPEs, indeed, provides a remarkable protection against oxidative damages: this effect was strictly dependent on the o-diphenolic content of the extracts. Moreover, the protective effects observable in cellular systems were compared with in vitro antioxidant properties, measured by using the FRAP (ferric reducing/antioxidant power) assay; the reducing ability of OOPEs strictly parallels their o-phenolic content. The linear relationship demonstrated between biological effects and antioxidant capacity measured by the FRAP assay allows us to propose the use of this rapid colorimetric method in assessing and certifying the antioxidant power of extra virgin olive oil.


Subject(s)
Oxidative Stress/drug effects , Phenols/pharmacology , Plant Oils/chemistry , Caco-2 Cells , Diet, Mediterranean , Erythrocytes , Humans , Olive Oil , Oxidation-Reduction , Reactive Oxygen Species
SELECTION OF CITATIONS
SEARCH DETAIL
...