Study of molecular mechanisms in cardio- and neuroprotection and possibility of modulation by nutraceutical phytocomponents

Ischemic preconditioning is a complex cardioprotective phenomenon that involves adaptive changes in cells and molecules. This adaptation occurs in a biphasic pattern: an early phase which develops after 1-2 h, and a late phase that develops after 12-24 h. While it is widely accepted that reactive oxygen species (ROS) are strongly involved in triggering ischemic preconditiong, it is not clear if they play a major role in the early or late phase of preconditioning and which are the mechanisms involved. Methylglyoxal, a metabolic compound formed mainly from the glycolytic intermediate glyceraldehyde-3-phosphate., is a precursor of advanced glycation end product (AGEs) .It is more reactive than glucose and shows a stronger ability to cross-link with protein amino groups to form AGEs. Methylglyoxal induced cytotoxicity may be at least partially responsible for cardiovascular and Alzheimer diseases. Methylglyoxal omeostasis is controlled by the glyoxalase system that consists of two enzyme, glyoxalase 1 (GLO1) and glyoxalase 2. In a recent study it was demonstrated that the transcriptional levels of GLO1 are controlled by NF-E2-related factor 2 (Nrf2). The isothiocyanate sulforaphane, derived from the hydrolysis of glucoraphanin abundantly present in broccoli, represents one of the most potent inducers of phase II enzymes through the Keap1–Nrf2 pathway. The aim of this thesis was evaluated molecular mechanisms in cardio- and neuroprotection and the possibility of modulation by nutraceutical phytocomponents This thesis show to one side that the protection induced by H2O2 is mediated by detoxifying and antioxidant phase II enzymes induction, regulated, not only by transcriptional factor Nrf2, but also by Nrf1; on the other side our data represent an innovative result because for the first time it was demonstrated the possibility of inducing GLO1 by SF supplementation.

Genetic characterization, population history and evolutionary medicine perspective in two native south american populations: Yanesha and Wichi

Two Amerindian populations from the Peruvian Amazon (Yanesha) and from rural lowlands of the Argentinean Gran Chaco (Wichi) were analyzed. They represent two case study of the South American genetic variability. The Yanesha represent a model of population isolated for long-time in the Amazon rainforest, characterized by environmental and altitudinal stratifications. The Wichi represent a model of population living in an area recently colonized by European populations (the Criollos are the population of the admixed descendents), whose aim is to depict the native ancestral gene pool and the degree of admixture, in relation to the very high prevalence of Chagas disease. The methods used for the genotyping are common, concerning the Y chromosome markers (male lineage) and the mitochondrial markers (maternal lineage). The determination of the phylogeographic diagnostic polymorphisms was carried out by the classical techniques of PCR, restriction enzymes, sequencing and specific mini-sequencing. New method for the detection of the protozoa Trypanosoma cruzi was developed by means of the nested PCR. The main results show patterns of genetic stratification in Yanesha forest communities, referable to different migrations at different times, estimated by Bayesian analyses. In particular Yanesha were considered as a population of transition between the Amazon basin and the Andean Cordillera, evaluating the potential migration routes and the separation of clusters of community in relation to different genetic bio-ancestry. As the Wichi, the gene pool analyzed appears clearly differentiated by the admixed sympatric Criollos, due to strict social practices (deeply analyzed with the support of cultural anthropological tools) that have preserved the native identity at a diachronic level. A pattern of distribution of the seropositivity in relation to the different phylogenetic lineages (the adaptation in evolutionary terms) does not appear, neither Amerindian nor European, but in relation to environmental and living conditions of the two distinct subpopulations.