Free radical biology & medicine
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Free Radic. Biol. Med. · Jul 2012
Randomized Controlled TrialOne year of pomegranate juice intake decreases oxidative stress, inflammation, and incidence of infections in hemodialysis patients: a randomized placebo-controlled trial.
Increased systemic inflammation and oxidative stress are well established as nontraditional key players in the pathogenesis of atherosclerosis and are also involved in the innate immunity dysregulation in hemodialysis (HD) patients. The study aim was to investigate the effect of 1-year intake of pomegranate juice, an antioxidant source, on oxidative stress, inflammation, and long-term clinical outcomes. A randomized placebo controlled double-blind trial was designed, enrolling 101 chronic HD patients to receive during each dialysis 100 cc of pomegranate juice, or matching placebo, three times a week for 1 year. ⋯ Pomegranate juice intake resulted in a significantly lower incidence rate of the second hospitalization due to infections. Furthermore, 25% of the patients in the pomegranate juice group had improvement and only 5% progression in the atherosclerotic process, while more than 50% of patients in the placebo group showed progression and none showed any improvement. Prolonged pomegranate juice intake improves nontraditional CV risk factors, attenuates the progression of the atherosclerotic process, strengthens the innate immunity, and thus reduces morbidity among HD patients.
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Free Radic. Biol. Med. · Jul 2012
ReviewAldosterone, oxidative stress, and NF-κB activation in hypertension-related cardiovascular and renal diseases.
The mineralocorticoid aldosterone regulates electrolyte and fluid balance and is involved in blood pressure homoeostasis. Classically, it binds to its intracellular mineralocorticoid receptor to induce expression of proteins influencing the reabsorption of sodium and water in the distal nephron. Aldosterone gained special attention when large clinical studies showed that blocking its receptor in patients with cardiovascular diseases reduced their mortality. ⋯ Subsequent studies confirmed the increase of oxidative stress markers in patients with chronic heart failure and in animal models of hyperaldosteronism. The effects of reactive oxygen species have been related to the activation of transcription factors, such as NF-κB. This review summarizes the present-day knowledge of aldosterone-induced oxidative stress and NF-κB activation in humans and different experimental models.
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Free Radic. Biol. Med. · Apr 2012
Early memory deficits precede plaque deposition in APPswe/PS1dE9 mice: involvement of oxidative stress and cholinergic dysfunction.
A large body of evidence has shown that cognitive deficits occur early, before amyloid plaque deposition, suggesting that soluble amyloid-β protein (Aβ) contributes to the development of early cognitive dysfunction in Alzheimer disease (AD). However, the underlying mechanism(s) through which soluble Aβ exerts its neurotoxicity responsible for cognitive dysfunction in the early stage of AD remains unclear so far. In this study, we used preplaque APPswe/PS1dE9 mice ages 2.5 and 3.5 months to examine alterations in cognitive function, oxidative stress, and cholinergic function. ⋯ In 3.5-month-old preplaque APPswe/PS1dE9 mice, correlational analyses revealed that the performance of impaired spatial memory was inversely correlated with soluble Aβ, MDA, and protein carbonyls, as well as being positively correlated with ACh, ChAT, SOD, and GSH-px; soluble Aβ level was inversely correlated with ACh, ChAT, SOD, and GSH-px, as well as being positively correlated with MDA and protein carbonyls; ACh level showed a significant positive correlation with ChAT, SOD, and GSH-px, as well as a significant inverse correlation with MDA and protein carbonyls. Collectively, this study provides direct evidence that increased oxidative damage and cholinergic dysfunction may be early pathological responses to soluble Aβ and involved in early memory deficits in the preplaque stage of AD. These findings suggest that early antioxidant therapy and improving cholinergic function may be a promising strategy to prevent or delay the onset and progression of AD.
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Free Radic. Biol. Med. · Apr 2012
ReviewMechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury.
Endothelial cells are covered by a delicate meshwork of glycoproteins known as the glycocalyx. Under normophysiological conditions the glycocalyx plays an active role in maintaining vascular homeostasis by deterring primary and secondary hemostasis and leukocyte adhesion and by regulating vascular permeability and tone. During (micro)vascular oxidative and nitrosative stress, which prevails in numerous metabolic (diabetes), vascular (atherosclerosis, hypertension), and surgical (ischemia/reperfusion injury, trauma) disease states, the glycocalyx is oxidatively and nitrosatively modified and degraded, which culminates in an exacerbation of the underlying pathology. ⋯ Specifically, the review focuses on (i) the mechanisms of glycocalyx degradation during hepatic ischemia/reperfusion, (ii) the molecular and cellular players involved in the degradation process, and (iii) its implications for hepatic pathophysiology. These topics are projected against a background of liver anatomy, glycocalyx function and structure, and the biology/biochemistry and the sources/targets of reactive oxygen and nitrogen species. The majority of the glycocalyx-related mechanisms elucidated for hepatic ischemia/reperfusion are extrapolatable to the other aforementioned disease states.
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Free Radic. Biol. Med. · Mar 2012
The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice.
A number of recent studies suggest that mitochondrial oxidative damage may be associated with atherosclerosis and the metabolic syndrome. However, much of the evidence linking mitochondrial oxidative damage and excess reactive oxygen species (ROS) with these pathologies is circumstantial. Consequently the importance of mitochondrial ROS in the etiology of these disorders is unclear. ⋯ MitoQ also significantly reduced mtDNA oxidative damage in the liver. Our data suggest that MitoQ inhibits the development of multiple features of the metabolic syndrome in these mice by affecting redox signaling pathways that depend on mitochondrial ROS such as hydrogen peroxide. These findings strengthen the growing view that elevated mitochondrial ROS contributes to the etiology of the metabolic syndrome and suggest a potential therapeutic role for mitochondria-targeted antioxidants.