Browsing by Author "Pellegrino, Daniela"

Now showing 1 - 3 of 3

Chronic kidney disease as an age related disease: new study perspectives fron animal models to hospitalized patents
(2019-04-11) La Russa, Daniele; Cerra, Maria Carmela; Pellegrino, Daniela; Montesanto, Alberto
Chronic kidney disease (CKD) is a major public health problem worldwide and its main consequences include the loss of renal function leading to end-stage renal disease (ESRD), an increased risk of cardiovascular disease (CVD), a significant increase in morbidity and mortality, and a decrease in health related quality of life. The risk of CKD increases with age, though there seems to be a complex relationship between ageing and this disease: elderly patients are overrepresented in the dialysis population and geriatric complications are highly detectable in younger patients with ESRD. This has led to the hypothesis of a premature biological ageing process of different organ systems associated with CKD. The present research work was based on translational approach to study the role of many CKD risk factors such as hypertension, oxidative stress/inflammation, obesity, and hyperuricemia with the aim of identifying new molecular mechanisms of kidney damage to prevent it by successful behaviour modifications. For this purpose, both human and animal models were used. Human pathological models: in both ESRD and obese patients, the role of oxidative stress, inflammation and hyperuricemia in progression and complications of CKD was investigated. Human physiological models: in a consistent healthy population, the oxidative status and its correlation with traditional cardiovascular risk factors were examined. In addition, the health history data of centenarian subjects was utilized to study the clinical and prognostic value of traditional cardiovascular risk factors in relation to mortality. Animal models: the mechanisms renal damage, induced by hypertension (Spontaneously Hypertensive Rat) and obesity (Cafeteria diet rats), were verified. In this context, the antioxidant and cytoprotective effects of a nutraceutical (Bergamot extract) on obesity was also tested. This multilevel approach has allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanism of CKD, in order to clarify the role of the new amplifying risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and non-modifiable risk factors.
I nitriti come molecola segnale: effetti diretti e indiretti sulla regolazione dell'attività cardiaca
(2012-11-20) Montesanti, Gabriella; Cerra, Maria Carmela; Canonaco, Marcello; Pellegrino, Daniela
Nitrite anion is a physiological NO storage form and an alternative way for NO generation, recently emerged as a cardioprotective endogenous modulator. Using Langendorff perfused rat hearts, as paradigms of mammals heart, we explored nitrite influence on the Frank-Starling response. We demonstrated that, like NO, exogenous nitrite improves the Frank-Starling response in rat heart as indicated by Left Ventricular Pressure (LVP) and the maximal rate of LVP decline (LVdP/dtmax), used as indexes of inotropism. Noteworthy, the minimal negative derivative of intraventricular pressure, LVdP/dt min, used as indexes of lusitropism, was positively affected by nitrite, suggesting the anion involvement not only in the systolic but also in the diastolic phase. This positive influence of nitrite was unaffected by endocardial endothelium impairment and NOS inhibition. In addition, the effect resulted sensitive to NO scavengers, independent on nitroxyl anion, and mediated by a cGMP/PKG-dependent pathway. These results suggest that nitrite acts as a physiological source of NO modulating the stretch-induced intrinsic regulation of the mammals heart. Moreover, nitrite affects numerous biological processes through NO-independent pathways (Bryan et al., 2005), including the S-nitrosylation of thiol-containing proteins (Foster et al., 2003). The mechanisms underlying these phenomena, until now not fully understood, are of great interest because of their cardiovascular therapeutic potential. In the last part of this study we analysed in the rat heart whether nitrite affect S-nitrosylation of cardiac proteins and the potential targets for S-nitrosylation. Rat hearts, perfused according to Langendorff, were exposed to nitrite and then analysed by Biotin Switch Method. We showed that nitrite increased the degree of S-nitrosylation of a broad range of membrane proteins. Further analysis, conducted on subfractioned proteins, allowed us to identify a high level of nitrosylation in a small range of plasmalemmal proteins (45-50 kDa). The increment in S-nitrosylation at this location was characterized by using an anti-Kir2.1 rabbit polyclonal antibody. We also verified that this effect of nitrite is preserved in the presence of the NO scavenger P-TIO. Finally, we wanted to investigate the direct effects of nitrite using two specific inhibitors of the major nitrite reductase in the heart, xantine oxidoreductase and citocrome P450 (allopurinol and ketoconazole respectively). The effect of nitrite in the presence of these inibitors is a bit reduced compared to control. A further analysis of this result, we used nitrite in the presence of N-acetyl-L-cysteine (NAC), a specific inhibitor of the nitroxyl anion (HNO). In this case, unlike that observed with the P-TIO, the effect of nitrite is significantly reduced. Our results suggest, for the first time, that nitrite represents a direct S-nitrosylating agent in cardiac tissues and that Kir2.1 channels are one of the targets. These observations are of relevance since they support the growing evidence that nitrite is not only a NO reserve but also a direct modulator of important functional cardiac proteins
I nitriti nel cuore di mammiferi e non-mammiferi: risorsa fisiologica di ossido nitrico e importante molecola segnale
(2014-03-25) Parisella, Maria Laura; Canonaca, Marcello; Pellegrino, Daniela