BIOMARKERS OF OXIDATIVE STRESS, INFLAMMATION AND ENDOTHELIAL FUNCTION TO STUDY THE ROLE OF BLUEBERRY BIOACTIVE COMPOUNDS IN VITRO AND IN VIVO.

The objective of the PhD thesis was to study the effect of blueberry and its bioactives in the modulation of biomarkers of oxidative stress, inflammation and endothelial function through in vitro and in vivo approaches. In particular, acute and chronic interventions were exploited in subjects with risk factors for cardiovascular disease to investigate the role of blueberry consumption in the modulation of DNA damage, pro-inflammatory cytokines, reactive hyperemia index, arterial stiffness, nitric oxide. At the same time, anthocyanin and phenolic blueberry fractions were used to explore their ability to reduce lipid accumulation in THP-1 macrophages, and to counteract THP-1 attachment to endothelial cells (HUVEC cell line) following stimulation with pro-inflammatory cytokines. The main results obtained in vivo showed that blueberry intake increased cell resistance against DNA damage and improved endothelial function; on the contrary, no effect was observed on markers of inflammation. The in vitro studies showed the capacity of blueberry bioactives to affect lipid accumulation and THP-1 adhesion to endothelial cells. In conclusion, the studies developed documented the beneficial role of blueberry in the modulation of biomarkers of oxidative stress and endothelial function in subjects exposed to risk factors. In addition, the potential antiatherogenic and antiatherosclerotic effect of blueberry bioactives was supported by the exploited in vitro approach.