Açai (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Because increased oxidative stress and impaired antioxidant defense mechanisms are important factors in the development of diabetic complications and many health claims have been reported for açai, the present study was undertaken to evaluate the possible protective effects of açai on the production of reactive oxygen species by neutrophils and on the liver antioxidant defense system in control and streptozotocin-induced diabetic rats. Diet supplementation with 2% açai was found to increase mRNA levels for gamma-glutamylcysteine synthetase and glutathione peroxidase in liver tissue and to decrease reactive oxygen species production by neutrophils. Compared to control animals, diabetic rats exhibited lower levels of mRNA coding for Zn-superoxide dismutase, glutathione peroxidase and gamma-glutamylcysteine synthetase and higher levels of reactive oxygen species production by neutrophils, thiobarbituric acid-reactive substances and carbonyl proteins in hepatic tissues. Although açai supplementation was not effective in restore gene expression of antioxidant enzymes in diabetic rats, it showed a protective effect, decreasing thiobarbituric acid-reactive substances levels and increasing reduced glutathione content in the liver. These findings suggest that açai can modulate reactive oxygen species production by neutrophils and that it has a significant favorable effect on the liver antioxidant defense system under fisiological conditions of oxidative stress and partially revert deleterious effects of diabetes in the liver.

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Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that has been shown to have antioxidant properties and to exhibit a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD. Moreover, TUDCA anti-inflammatory properties have been reported in glial cells, making it a prominent therapeutic agent in PD. Here, we used C57BL/6 mice injected with MPTP in a sub-acute paradigm aiming to investigate if the neurotoxic effects of MPTP could be extended to the cerebral cortex. In parallel, we evaluated the anti-oxidant, neuroprotective and anti-inflammatory effects of TUDCA. The anti-inflammatory mechanisms elicited by TUDCA were further dissected in microglia cells. Our results show that MPTP leads to a decrease of ATP and activated AMP-activated protein kinase levels in mice cortex, and to a transient increase in the expression of antioxidant downstream targets of nuclear factor erythroid 2 related factor 2 (Nrf-2), and parkin. Notably, MPTP increases pro-inflammatory markers, while down-regulating the expression of the anti-inflammatory protein Annexin-A1 (ANXA1). Importantly, we show that TUDCA treatment prevents the deleterious effects of MPTP, sustains increased levels of antioxidant enzymes and parkin, and most of all negatively modulates neuroinflammation and up-regulates ANXA1 expression. Additionally, results from cellular models using microglia corroborate TUDCA modulation of ANXA1 synthesis, linking inhibition of neuroinflammation and neuroprotection by TUDCA. 2014). PD is mainly a motor disorder, pathologically characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc), severe striatal dopamine depletion, and by the presence of intracellular inclusions containing aggregates of α-synuclein known as Lewy bodies (

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Background: It is generally agreed that elderly subjects undergo progressive deterioration of their immune responsiveness, which leads to an increased susceptibility to autoimmune processes, neoplasm and inflammation. Thus there is a general consensus that regulation of inflammation results from a balance between pro-inflammatory and anti-inflammatory pathways. Objective: The present study aimed to investigate the possible alterations of cyclic AMP/protein kinase A (cAMP/PKA) and p38 mitogen-activated protein kinase (p38 MAPK) pathway signaling (reactive oxygen species (ROS) generation) and inositol 1,4,5-triphosphate (InsP3) production by neutrophils during the aging process. Methods: Age-induced ROS generation and InsP3 production were studied in healthy subjects ranging in age from 20 to 80 years. The subjects were divided into six age groups: (I) 20–29, (II) 30–39, (III) 40–49, (IV) 50–59, (V) 60–69, and (VI) 70–80 years old. The effect of cAMP, H89 (inhibitor PKA), and PD169316 (inhibitor p38 MAPK) on ROS production was quantified in a luminol-dependent chemiluminescence assay (relative light units/min) and by InsP3 release (cpm). Results: Our results demonstrated a lack of dibutyryl cAMP inhibitory effects on ROS generation and InsP3 production by granulocytes from PKA-dependent 50-year-olds. However, the inhibitory effect of cAMP is restored in neutrophils after the age of 50 years when p38 MAPK signaling is inhibited. Conclusions: The present study may be important towards a better understanding of the high susceptibility to infections and age-related inflammatory and deregulation diseases. The alteration of cAMP/PKA and p38 MAPK signaling pathways enhances the inflammatory process.

Schistosomiasis represents a condition in which every aspect of the disease, starting from skin invasion of the cercariae to egg laying by adult worms, incites a tissue response from the vertebrate host. This response, whether acute or chronic, leads to the appearance of reporter molecules of tissue injury in bodily fluids that could be surveyed as markers for disease diagnosis, status and prognosis. In this scenario, the serum proteome associated with a schistosome infection remains poorly explored; particularly by the use of high-throughput mass spectrometric instrumentation. In this study, we aimed to comparatively examine the serum proteome of control versus infected BALB/c mice, spanning the interval between the onset of egg laying and the peak of the acute phase of infection. Compositional analysis of the sera, using one dimensional reversed-phase fractionation of tryptic peptides coupled to mass spectrometry, allowed identification of 453 constituents. Among these, over 30% (143 molecules) were differentially present comparing sera from infected and non-infected mice, as revealed by quantitative label-free shotgun approach. The majority of proteins exhibiting altered levels was categorised as belonging to immune response (acute phase-related proteins) followed by those linked to lipid transport and metabolism. Inspection of the lipid profile from control and infected individuals demonstrated more pronounced and significant alterations in triglycerides, VLDL and HDL fractions (p<0,001), attesting for a disturbance in circulating lipid molecules, and suggesting a key role in host-parasite interactions. Our findings provide a global view of the serum proteome in the context of experimental schistosomiasis during the acute phase of infection. It contributes by listing key molecules that could be monitored to inform on the associated inflammatory disease status. We hope it will shed light into uncovered aspects of the Schistosoma mansoni parasitism in the vertebrate host, particularly those related to modulation of the lipid metabolism mediating immune responses.

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