RESUMO
Fucoxanthin is the most abundant carotenoid found in marine brown algae that exhibits several healthy properties. Dietary fucoxanthin is metabolized in the intestine, plasma, and other tissues to various metabolites, including fucoxanthinol. In this regard, the contribution of fucoxanthinol to the healthy properties of its precursor, fucoxanthin, against pathogenetic events associated with neurodegenerative diseases remains unexplored. Here, we evaluated and compared the antioxidant and neuroprotective effects of the carotenoids fucoxanthin and fucoxanthinol in in vitro models of Alzheimer's (AD) and Parkinson's (PD) disease. Neuronal SH-SY5Y cells were used to evaluate the antioxidant properties of the carotenoids against ABTS radical in the membrane and cytoplasm and oxidative stress elicited by tert-butyl hydroperoxide using the 2',7'-dichlorodihydrofluorescein diacetate probe. We also assessed the ability of the carotenoids to increase the glutathione (GSH) and activate the Nrf2/Keap1/ARE pathway using the monochlorobimane probe and western blotting method, respectively. The neuroprotective effects of the carotenoids against the neurotoxicity generated by oligomers of Beta-Amyloid (1-42) peptide (OAß) and 6-hydroxydopamine (6-OHDA), which are neurotoxins of AD and PD, respectively, were finally evaluated in the same neuronal cells using the thiazolyl blue tetrazolium bromide assay. Both carotenoids could reach the cytoplasm, which explains the mainly free radical scavenging activity at this level. Notably, fucoxanthinol had higher and lower antioxidant activity than fucoxanthin at extracellular and cellular levels. Although studied carotenoids exerted the ability to activate the Nrf2/Keap1/ARE pathway, leading to an increase of intracellular GSH, our results suggested that the antioxidant activity of the carotenoids could be mainly attributed to their radical scavenging activity in neuronal membrane and cytoplasm, where they accumulate. Fucoxanthinol also shared similar neuroprotective effects as fucoxanthin against the neurotoxicity generated by OAß and 6-OHDA, suggesting a potential neuroprotective contribution to the action of fucoxanthin administered as a food supplement in in vivo experimental models. These results encourage further research to evaluate the bioavailability of fucoxanthinol and other metabolites of fucoxanthin at the brain level to elucidate the dietary neuroprotective potential of fucoxanthin.
RESUMO
The production of reactive oxygen species (ROS) in the brain is homeostatically controlled and contributes to normal neural functions. Inefficiency of control mechanisms in brain aging or pathological conditions leads to ROS overproduction with oxidative neural cell damage and degeneration. Among the compounds showing therapeutic potential against neuro-dysfunctions induced by oxidative stress are the guanine-based purines (GBPs), of which the most characterized are the nucleoside guanosine (GUO) and the nucleobase guanine (GUA), which act differently. Indeed, the administration of GUO to in vitro or in vivo models of acute brain injury (ischemia/hypoxia or trauma) or chronic neurological/neurodegenerative disorders, exerts neuroprotective and anti-inflammatory effects, decreasing the production of reactive radicals and improving mitochondrial function via multiple molecular signals. However, GUO administration to rodents also causes an amnesic effect. In contrast, the metabolite, GUA, could be effective in memory-related disorders by transiently increasing ROS production and stimulating the nitric oxide/soluble guanylate cyclase/cGMP/protein kinase G cascade, which has long been recognized as beneficial for cognitive function. Thus, it is worth pursuing further studies to ascertain the therapeutic role of GUO and GUA and to evaluate the pathological brain conditions in which these compounds could be more usefully used.
RESUMO
AIMS: Acute heart failure (AHF) represents a frequent cause of hospitalization and is associated with significant mortality among elderly patients. Risk assessment models like the prognostic nutritional index (PNI) have been proposed to stratify the risk of death and identify patients requiring more intensive levels of care. We evaluated the predictive value of PNI for in-hospital and overall mortality in a cohort of consecutive elderly patients hospitalized for AHF. METHODS AND RESULTS: Prognostic nutritional index, laboratory, and clinical parameters were collected upon admission. PNI values were calculated from albumin concentration and lymphocyte count and reported on a continuous scale with lower values indicating worse prognosis. The primary outcome was overall all-cause mortality defined as death from any cause occurring during hospitalization up to 6 months after discharge. Cox proportional regression analysis was used to calculate hazard ratios (HRs) and the relative 95% confidence intervals (CIs). The study population included 344 patients (median age 84 years, range 65 to 101). During a median follow-up of 158 days (range 2 to 180 days), 75 patients (21.8%) died of whom 28 (8.1%) died during hospitalization. The median PNI was 34 (range 17 to 55). In univariable analysis, PNI was inversely associated with overall mortality (HR 0.90; 95% CI, 0.87 to 0.94) and in-hospital mortality (HR 0.91; 95% CI, 0.85 to 0.98). In multivariable analysis, PNI remained a significant predictor of overall mortality (HR 0.93; 95% CI, 0.89 to 0.98) after adjustment for age, anaemia, NT-proBNP values, and bedridden status. PNI values ≤34 were associated with a two-fold higher risk of overall mortality (HR 2.54; 95% CI, 1.52 to 4.24) and three-fold higher risk of in-hospital mortality (HR 3.37; 95% CI, 1.14 to 9.95). CONCLUSIONS: Low PNI values are associated with short-term and long-term mortality among elderly patients hospitalized for acute decompensated heart failure. Future studies are warranted to confirm these findings and evaluate the use of PNI to guide therapeutic decisions.