Oxidised LDL up-regulate CD36 expression by the Nrf2 pathway in 3T3-L1 preadipocytes.

The effect of oxLDL on CD36 expression has been assessed in preadipocytes induced to differentiate. Novel evidence is provided that oxLDL induce a peroxisome proliferator-activated receptor gamma-independent CD36 overexpression, by up-regulating nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2). The nuclear translocation of Nrf2 appeared to depend on PKC pathway activation. In adipocytes, the CD36 up-regulation may indicate a compensation mechanism to meet the demand of excess oxLDL and oxidised lipids in blood, reducing the risk of atherogenesis. Besides strengthening the hypothesis that oxLDL can contribute to the onset of insulin-resistance, data herein presented highlight the significance of oxLDL-induced CD36 overexpression within the cellular defence response.

Modulatory effects of polyphenols on apoptosis induction: relevance for cancer prevention.

Polyphenols, occurring in fruit and vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products, have been demonstrated to have clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. However, it has become clear that, in complex biological systems, polyphenols exhibit several additional properties which are yet poorly understood. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathological processes, since too little or too much apoptosis can lead to proliferative or degenerative diseases, respectively. Cancer cells are characterized by a deregulated proliferation, and/or an inability to undergo programmed cell death. A large body of evidence indicates that polyphenols can exert chemopreventive effects towards different organ specific cancers, affecting the overall process of carcinogenesis by several mechanisms: inhibition of DNA synthesis, modulation of ROS production, regulation of cell cycle arrest, modulation of survival/proliferation pathways. In addition, polyphenols can directly influence different points of the apoptotic process, and/or the expression of regulatory proteins. Although the bulk of data has been obtained in in vitro systems, a number of clinical studies suggesting a preventive and therapeutic effectiveness of polyphenols in vivo is available. However, a deeper knowledge of the underlying mechanisms responsible for the modulation of apoptosis by polyphenols, and their real effectiveness, is necessary in order to propose them as potential chemopreventive and chemotherapeutic candidates for cancer treatment.

Tyrosol, the major extra virgin olive oil compound, restored intracellular antioxidant defences in spite of its weak antioxidative effectiveness.

BACKGROUND AND AIM: Extra virgin olive oil has been associated with a reduced incidence of risk factors for coronary heart disease also owing to the presence of antioxidant biophenols. This study compared the protective effects of tyrosol and hydroxytyrosol, two biophenols greatly different in antioxidant power, on J774 A.1-mediated oxidation of LDL. METHODS AND RESULTS: Cell-mediated oxidation of LDL was evaluated by TBARS formation, and relative electrophoretic mobility increase. Redox imbalance was studied by: (i) cytofluorimetric determination of intracellular ROS and GSH, and (ii) evaluation of GSH-related enzyme activities and gene expressions by colorimetric and RT-PCR analyses, respectively. The cellular uptake of the biophenols was evaluated by HPLC. Both biophenols inhibited cell-mediated oxidation of LDL but to a different extent (100% hydroxytyrosol vs 40% tyrosol), and counteracted the impairment of antioxidant cellular defence, i.e., GSH and related enzymes. Tyrosol was effective in inhibiting about 30% of ROS production only at later time-points (12h for superoxide, 24h for hydrogen peroxides). Interestingly, both biophenols were effective when added to the cells for 2h and removed before LDL treatment. This was probably related to cell-biophenol interactions: hydroxytyrosol was rapidly found inside the cells (1.12+/-0.05ng/mg cell protein) and disappeared within 18h, while tyrosol accumulated intracellularly with time (0.68+/-0.09 vs 1.72+/-0.13ng/mg cell protein at minute 5 and hour 18, respectively). CONCLUSIONS: In spite of its weak antioxidant activity, tyrosol was effective in preserving cellular antioxidant defences, probably by intracellular accumulation. These findings give further evidence in favour of olive oil consumption to counteract cardiovascular diseases.

Polyphenols, dietary sources and bioavailability.

Fruit and beverages such as tea and red wine represent the main sources of polyphenols. Despite their wide distribution, the healthy effects of dietary polyphenols have come to the attention of nutritionists only in the last years. The main factor responsible for the delayed research on polyphenols is the variety and the complexity of their chemical structure. Emerging findings suggest a large number of potential mechanisms of action of polyphenols in preventing disease, which may be independent of their conventional antioxidant activities. To establish evidence for the effects of polyphenol consumption on human health and to better identify which polyphenols provide the greatest effectiveness in disease prevention, it is first of all essential to determine the nature and the distribution of these compounds in our diet, and secondly to better know their bioavailability.

Polyphenols, intracellular signalling and inflammation.

Excessive inflammation is considered as a critical factor in many human diseases, including cancer, obesity, type II diabetes, cardiovascular diseases, neurodegenerative diseases and aging. Compounds derived from botanic sources, such as phenolic compounds, have shown anti-inflammatory activity in vitro and in vivo. Recent data suggest that polyphenols can work as modifiers of signal transduction pathways to elicit their beneficial effects. These natural compounds express anti-inflammatory activity by modulation of pro-inflammatory gene expression such as cyclooxygenase, lipoxygenase, nitric oxide synthases and several pivotal cytokines, mainly by acting through nuclear factor-kappa B and mitogen-activated protein kinase signalling. This review will discuss recent data on the control of inflammatory signalling exerted by some dietary polyphenols contained in Mediterranean diet. A clear understanding of the molecular mechanisms of action of phenolic compounds is crucial in the valuation of these potent molecules as potential prophylactic and therapeutic agents.

[Polyphenols and endogenous antioxidant defences: effects on glutathione and glutathione related enzymes]. / Polifenoli e difese antiossidanti endogene: effetti sul glutatione e sugli enzimi ad esso correlati.

Among diet antioxidants, polyphenols, naturally occurring in vegetables, fruits and plant-derived beverages such as tea, red wine, and extra virgin olive oil, are the most abundant ones. In vitro cell culture experiments have shown that polyphenols possess antioxidant properties, and it is thought that these activities can contribute to the prevention of several oxidative stress-associated diseases. It has however become clear that the mechanisms of action of polyphenols go beyond their intrinsic reducing capabilities, being able to exert other additional effects that are as yet poorly understood. This article gives an overview of the most recent data on the subject and describe the additional functions that polyphenols can have in biological systems, focusing on their effects on glutathione and its related enzymes. Evidence is provided of a tight connection between exogenous and endogenous antioxidants that appear to act in a coordinated fashion. Experimental data indicate that polyphenols may offer an indirect protection by activating endogenous defense systems. It is reasonable to hypothesize that this is achieved, at least in part, through antioxidant responsive elements (ARE) present in the promoter regions of many of the genes inducible by oxidative and chemical stress. The latest studies strongly suggest that dietary polyphenols can stimulate antioxidant enzyme transcription through ARE.

Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes.

Polyphenols are wide variety of compounds that occur in fruits and vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. Several polyphenols have been demonstrated to have clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. However, this concept appears now to be a simplistic way to conceive their activity. Evidence is indeed accumulating that polyphenols might exert several other specific biological effects that are as yet poorly understood. In this article we review the most recent data on the subject and describe the additional functions that polyphenols can have in biological systems, focusing on their effects on glutathione and its related enzymes. Experimental data indicate that polyhenols may offer an indirect protection by activating endogenous defense systems. Several lines of evidence suggest a tight connection between exogenous and endogenous antioxidants that appear to act in a coordinated fashion. It is reasonable to hypothesize that this is achieved, at least in part, through antioxidant responsive elements (AREs) present in the promoter regions of many of the genes inducible by oxidative and chemical stress. The latest studies strongly suggest that dietary polyphenols can stimulate antioxidant transcription and detoxification defense systems through ARE.