Abstract: Since any significant modification in the Se status, leading to changes in the activity of the seleno-enzymes, may have important consequences on the susceptibility of tissues to oxidative stress, considerable efforts have been made upon increasing Se dietary intake. In this respect, an important debate is still open about the bioavailability and the effectiveness of Se, and more generally nutrients, in supplements compared with foods. Using male Wistar rats, we have compared the effectiveness of two different diets in which an adequate Se content (0.1 mg/kg) was achieved by adding the element as sodium selenite or as component of a lyophilized Se-enriched food, in the counteraction of an oxidative stress induced by intraperitoneal administration of adriamycin. Both Se-enriched diets were able to reduce the consequences of the oxidative stress in liver, mainly by increasing glutathione peroxidase activity. This increase was more evident in rats fed on the diet enriched with the lyophilized food, probably due to the different chemical forms of Se, or to other components of the food itself. Although further studies are needed, data herein presented may contribute to the characterization of the effectiveness of Se from different sources, foods or supplements, in the light of dietary advice to the population concerning improvement of Se intake.

Abstract: In cardiac cells the effects of n-3 PUFAs on the whole genome are still unknown despite their recognized cardioprotective effects and ability to modulate gene expression. We have evaluated the effects of n-3 PUFAs supplementation on the global gene expression profile in cultured neonatal rat cardiomyocytes, detecting many genes related to lipid transport and metabolism among the upregulated ones. Many of the downregulated genes appeared related to inflammation, cell growth, extracellular and cardiac matrix remodelling, calcium movements and ROS generation. Our data allow to speculate that the cardioprotective effect of n-3 PUFAs is related to a direct modulation of genes in cardiac cells.

Abstract: Many reports indicate that dietary selenium, potentially increasing the activity of glutathione peroxidase, could offer protection against free-radical-induced damage. The effects of diets moderately enriched in selenium, as sodium selenite or as a lyophilized selenium-rich food, were studied in rats. Adriamycin, an anticancer drug causing a free-radical-mediated cardiotoxicity, was administered intraperitoneally to some rats. The onset of an oxidative damage was indicated by the increase in the plasma level of reactive oxygen metabolites coupled to a decrease in the total antioxidant activity but without modification of glutathione peroxidase activity, which were observed in all rats, independent of the dietary treatment. On the contrary, in the heart, selenium supplementation caused an increase in the total antioxidant activity, glutathione concentration, and glutathione peroxidase and catalase activities leading to a decreased generation of reactive oxygen metabolites. These results clearly indicate that a moderate Se dietary supplementation counteracts adriamycin-induced cardiotoxicity by preservation of endogenous antioxidants.

Abstract: Dietary selenium, vitamin B6 and fatty acids modulate both tissue acyl composition by regulating polyunsaturated fatty acid metabolism and antioxidant defences by influencing glutathione peroxidase activity. Alteration in the intake of one of them could therefore lead to different results depending on the intake of the others. To clarify this complex relationship, in the present study we have evaluated the modifications occurring in fatty acid composition and glutathione peroxidase activity in total liver and liver microsomes of rats fed diets containing the same amount of selenium, but different vitamin B6 content and fatty acid composition. Our data indicate that both acyl composition and glutathione peroxidase activity are greatly influenced not only by vitamin B6 deficiency, but also by the diet unsaturation degree. This study underlines that not only selenium availability but also other nutrients can modulate glutathione peroxidase activity.

Abstract: Since in the aged heart an increased basal production of reactive oxygen species (ROS) has been demonstrated, and the resistance to ROS attack could be ameliorated by antioxidant supplementation, we verified the protective effect of selenium, as sodium selenite (SS) or seleno methionine (SM), in cultured rat cardiomyocytes aged in vitro. In normoxia, glutathione peroxidase (GPx) activity and total antioxidant activity were higher in old than in young cardiomyocytes, suggesting the existence of a compensatory increase of antioxidant defenses. When aged cells were submitted to hypoxia/reoxygenation, GPx activity was not modified; while total antioxidant activity decreased, conjugated diene level increased. Selenium supplementation, particularly as SM, was able to increase GPx, and consequently total antioxidant activity, and to decrease conjugated diene production. The observed ability of selenium supplementation to protect aged cardiomyocytes from hypoxia/reoxygenation damage underlines the importance of an optimal selenium dietary intake, particularly in the elderly.

Abstract: BACKGROUND AND AIMS: Peroxidation of membrane lipids, altering cell integrity and function, plays an important part in the onset and development of cardiac damage following ischemia and reperfusion. Cells maintain their membrane lipid homeostasis by substituting peroxidized lipids with new polyunsaturated fatty acids. The microsomal enzymatic system converting essential fatty acids to highly unsaturated fatty acids (HUFAs) contributes to this repairing mechanism. The membrane of the endoplasmic reticulum could be one of the potential targets of free radicals generated in ischemia/reperfusion, thus causing a reduced efficacy of the system required for HUFA biosynthesis. To verify this hypothesis, and the consequent modification in fatty acid composition, we exposed cultured rat cardiomyocytes to different periods of hypoxia (H), eventually followed by reoxygenation (R). Furthermore, the effectiveness of antioxidants like alpha-tocopherol and a green tea extract in counteracting H/R damage towards HUFA biosynthesis was tested. METHODS AND RESULTS: Linoleic (LA) and alpha-linolenic acid (ALA) conversion was measured by pre-labelling cells with [1-14C]LA or [1-14C]ALA for 1 h; total lipid fatty acid composition was determined by gas chromatographic analysis. H profoundly affected HUFA biosynthesis, and this effect was much more evident on LA than on ALA. Conversion of both substrates was partially restored during R due to the readmission of the final acceptor of the desaturating complex. Fatty acid composition data were in agreement with the modifications observed in essential fatty acid conversion. Antioxidant protection appeared to be related to the duration of H, and to be more effective during H than during R. CONCLUSION: This study points out the importance of possessing good antioxidant defenses not only after, but mainly prior to the onset of H.