Wine and olive oil, essential components of the Mediterranean diet, are considered important factors for a healthy life style. Tyrosol (T) and caffeic acid (CA) are found in both extra virgin olive oil and in white wine. Three white wines from the northeast Italy and four white wines from Germany were analyzed for their content of T and CA. These compounds were tested for their antioxidant activity and their capacity to modulate three different cytokines: IL-1 beta, IL-6, and TNF-alpha, which are currently considered to be the major cytokines influencing the acute phase of the inflammatory response. Furthermore, the antioxidant activity of T and CA was analyzed by monitoring the oxidation of a redox-sensitive probe by using laser scanning confocal microscopy. T and CA, applied at nanomolar range, were found to significantly reduce the generation of oxidants induced by azobis-amidinopropanedihydrochloride. Peripheral blood mononuclear cells (PBMC) from healthy volunteers were incubated at 37 degrees C for 12 hours with 100 ng LPS (E. coli and P. maltofilia). Increasing doses of T and CA (150 nM to 300 microM) were added and cell-associated IL-1 beta and TNF-alpha were determined by immunoreactive tests after three freeze-thaw cycles. IL-6 release was also determined in cell surnatants. LPS-stimulated PBMC showed a significant increase in cytokine release, while T and CA, used at nanomolar concentrations, were able to modulate their expression. Taken together, these results suggest a remarkable effect of white wine non-alcoholic compounds on oxidative stress and inflammatory reaction.

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Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. The precise mechanism by which CsA causes renal injury is not known. Reactive oxygen species (ROS) have been shown to play a role, since CsA-induced renal lipid peroxidation is attenuated in vivo and in vitro by the concomitant administration of antioxidants such as vitamin E. We show here the effect of the antioxidant melatonin (MLT), a hormone produced by the pineal gland during the dark phase of the circadian cycle, in a model of CsA nephrotoxicity in the isolated and perfused rat kidney. Kidneys isolated from rats were divided into seven groups. At the end of perfusion, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), metabolites of nitric oxide NO2- + NO3- were measured and histopathological examination was performed. CsA treatment induced a significant increase in MDA + 4-HDA while not affecting the nitric oxide metabolite level. MLT remarkably prevented glomerular collapse and tubular damage as revealed by morphometric analysis. Our study suggests that lipid peroxidation is an early important event in the pathogenesis of CsA nephrotoxicity and that MLT is able to protect kidneys from CsA at a relatively low concentration.