Manipolazione del metabolismo degli xenobiotici da frutta convenzionale ed attività chemiopreventiva

A reduced cancer risk associated with fruit and vegetable phytochemicals initially dictated chemopreventive approaches focused on specific green variety consumption or even single nutrient supplementations. However, these strategies not only failed to provide any health benefits but gave rise to detrimental effects. In parallel, public-health chemoprevention programmes were developed in the USA and Europe to increase whole vegetable consumption. Among these, the National Cancer Institute (NCI) sponsored plan “5 to 9 a day for a better health” was one of the most popular. This campaign promoted wide food choice through the consumption of at least 5 to 9 servings a day of colourful fruits and vegetables. In this study the effects of the diet suggested by NCI on transcription, translation and catalytic activity of both xenobiotic metabolizing (XME) and antioxidant enzymes were studied in the animal model. In fact, the boost of both antioxidant defences and “good” phase-II together with down-regulation of “bad” phase-I XMEs is still considered one of the most widely-used strategies of cancer control. Six male Sprague Dawley rats for each treatment group were used. According to the Italian Society of Human Nutrition, a serving of fruit, vegetables and leafy greens corresponds to 150, 250 and 50 g, respectively, in a 70 kg man. Proportionally, rats received one or five servings of lyophilized onion, tomato, peach, black grape or lettuce – for white, red, yellow, violet or green diet, respectively - or five servings of each green (“5 a day” diet) by oral gavage daily for 10 consecutive days. Liver subcellular fractions were tested for various cytochrome P450 (CYP) linked-monooxygenases, phase-II supported XMEs such as glutathione S-transferase (GST) and UDP-glucuronosyl transferase (UDPGT) as well as for some antioxidant enzymes. Hepatic transcriptional and translational effects were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. dROMs test was used to measure plasmatic oxidative stress. Routine haematochemical parameters were also monitored. While the five servings administration didn’t significantly vary XME catalytic activity, the lower dose caused a complex pattern of CYP inactivation with lettuce exerting particularly strong effects (a loss of up to 43% and 45% for CYP content and CYP2B1/2-linked XME, respectively; P<0.01). “5 a day” supplementation produced the most pronounced modulations (a loss of up to 60% for CYP2E1-linked XME and a reduction of CYP content of 54%; P<0.01). Testosterone hydroxylase activity confirmed these results. RT-PCR and Western blot analysis revealed that the “5 a day” diet XMEs inactivations were a result of both a transcriptional and a translational effect while lettuce didn’t exert such effects. All administrations brought out none or fewer modulation of phase-II supported XMEs. Apart from “5 a day” supplementation and the single serving of lettuce, which strongly induced DT- diaphorase (an increase of up to 141 and 171%, respectively; P<0.01), antioxidant enzymes were not significantly changed. RT-PCR analysis confirmed DT-diaphorase induction brought about by the administration of both “5 a day” diet and a single serving of lettuce. Furthermore, it unmasked a similar result for heme-oxygenase. dROMs test provided insight into a condition of high systemic oxidative stress as a consequence of animal diet supplementation with “5 a day” diet and a single serving of lettuce (an increase of up to 600% and 900%, respectively; P<0.01). Haematochemical parameters were mildly affected by such dietary manipulations. According to the classical chemopreventive theory, these results could be of particular relevance. In fact, even if antioxidant enzymes were only mildly affected, the phase-I inactivating ability of these vegetables would be a worthy strategy to cancer control. However, the recorded systemic considerable amount of reactive oxygen species and the complexity of these enzymes and their functions suggest caution in the widespread use of vegan/vegetarian diets as human chemopreventive strategies. In fact, recent literature rather suggests that only diets rich in fruits and vegetables and poor in certain types of fat, together with moderate caloric intake, could be associated with reduced cancer risk.

Well-being, distress and health status in a population of adolescent students

The present work explores the psychosocial issues emerging from a large cross-sectional study aimed to assess the prevalence, clinical manifestations, and psychosocial correlates of hyperandrogenism in a population of Italian high school students. Participants were 1804 adolescents, aged between 15 and 19 years, who volunteered to fill in a package of self-report questionnaires (including the Psychosocial Index, the Symptom Questionnaire and Ryff’s Psychological Well-Being scales for the assessment of psychological aspects) and undergo a comprehensive physical examination. Significant gender differences were found with regard to psychological distress, with females reporting higher scores compared with males, but not on well-being dimensions. The relationships of well-being to distress were found to be complex. Although inversely associated, well-being and ill-being appeared to be distinct domains of mental functioning. The evaluation of the moderating effects of well-being in the association between stress and psychological distress indicated that well-being may act as a protective factor, contributing to less pronounced psychological distress as stress levels increased. Higher rates of somatic complaints were found among current smokers. However, substance use (i.e., smoking and drug use) was also found to be positively associated with some well-being dimensions. A considerable number of participants were found to present with disordered eating symptoms, particularly females, and associated higher stress levels and lower quality of life. Sport activities were found to favourably affect psychological health. As to clinical signs of hyperandrogenism, a significant impairment in psychosocial functioning was found among females, whereas no effects on psychological measures could be detected among males. Subgroups of adolescents with distinct clinical and psychological characteristics could be identified by means of cluster analysis. The present study provides new insights into better understanding of the complex relationships between well-being, distress and health status in the adolescent population, with important clinical implications.