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      Astaxanthin Supplementation Delays Physical Exhaustion and Prevents Redox Imbalances in Plasma and Soleus Muscles of Wistar Rats

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          Abstract

          Astaxanthin (ASTA) is a pinkish-orange carotenoid commonly found in marine organisms, especially salmon. ASTA is a powerful antioxidant and suggested to provide benefits for human health, including the inhibition of LDL oxidation, UV-photoprotection, and prophylaxis of bacterial stomach ulcers. Exercise is associated to overproduction of free radicals in muscles and plasma, with pivotal participation of iron ions and glutathione (GSH). Thus, ASTA was studied here as an auxiliary supplement to improve antioxidant defenses in soleus muscles and plasma against oxidative damage induced by exhaustive exercise. Long-term 1 mg ASTA/kg body weight (BW) supplementation in Wistar rats (for 45 days) significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP) and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion. We also provided significant discussion about a putative “mitochondrial-targeted” action of ASTA based on previous publications and on the positive results found in the highly mitochondrial populated (oxidative-type) soleus muscles here.

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          Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling.

          The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein-protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling.
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            Applicability of an improved Trolox equivalent antioxidant capacity (TEAC) assay for evaluation of antioxidant capacity measurements of mixtures

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              Cellular mechanisms of muscle fatigue.

              R Fitts (1993)
              Fatigue, defined as the failure to maintain the required or expected power output, is a complex problem, since multiple factors are clearly involved, with the relative importance of each dependent on the fiber type composition of the contracting muscles(s), and the intensity, type, and duration of the contractile activity. The primary sites of fatigue appear to be within the muscle cell itself and for the most part do not involve the central nervous system or the neuromuscular junction. The major hypotheses of fatigue center on disturbances in the surface membrane, E-C coupling, or metabolic events. The cell sites most frequently linked to the etiology of skeletal muscle fatigue are shown in Figure 1. Skeletal muscles are composed of at least four distinct fiber types (3 fast twitch and 1 slow twitch), with the slow type I and fast type IIa fibers containing the highest mitochondrial content and fatigue resistance. Despite fiber type differences in the degree of fatigability, the contractile properties undergo characteristic changes with the development of fatigue that can be observed in whole muscles, single motor units, and single fibers. The Po declines, and the contraction and relaxation times are prolonged. Additionally, there is a decrease in the peak rate of tension development and decline and a reduced Vo. Changes in Vo are more resistant to fatigue than Po and are not observed until Po has declined by at least 10% of its initial prefatigued value. However, the reduced peak power by which fatigue is defined results from both a reduction in Vo and Po. In the absence of muscle fiber damage, the prolonged relaxation time associated with fatigue causes the force-frequency curve to shift to the left, such that peak tensions are obtained at lower frequencies of stimulation. In a mechanism not clearly understood, the central nervous system senses this condition and reduces the alpha-motor nerve activation frequency as fatigue develops. In some cases, selective LFF develops that displaces the force-frequency curve to the right. Although not proven, it appears likely that this condition is associated with and likely caused by muscle injury, such that the SR releases less Ca2+ at low frequencies of activation. Alternatively, LFF could result from a reduced membrane excitability, such that the sarcolemma action potential frequency is considerably less than the stimulation frequency.(ABSTRACT TRUNCATED AT 400 WORDS)
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                12 December 2014
                December 2014
                : 6
                : 12
                : 5819-5838
                Affiliations
                [1 ]Institute of Physical Activity and Sports Sciences (ICAFE), Cruzeiro do Sul University, 01506-000 Sao Paulo, Brazil; E-Mails: tatianapolotow@ 123456hotmail.com (T.G.P.); crisvardaris@ 123456gmail.com (C.V.V.); andreamihaliuc@ 123456hotmail.com (A.R.M.); masg_je@ 123456yahoo.com.br (M.S.G.); douganini@ 123456uol.com.br (D.G.)
                [2 ]School of Physical Education and Sports (EEFE), University of Sao Paulo (USP), 05508-900 Sao Paulo, Brazil; E-Mail: benepe@ 123456usp.br
                [3 ]Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, NIEHS, Research Triangle Park, Durham, NC 27709, USA
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: marcelo.barros@ 123456cruzeirodosul.edu.br ; Tel.: +55-11-3385-3103; Fax: +55-11-2037-5700.
                Article
                nutrients-06-05819
                10.3390/nu6125819
                4277001
                25514562
                c1da0ab8-0f27-4b1b-982e-acb5d4b4dab1
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 August 2014
                : 06 November 2014
                : 13 November 2014
                Categories
                Article

                Nutrition & Dietetics
                carotenoid,exercise,iron,uric acid,oxidative stress,mitochondria
                Nutrition & Dietetics
                carotenoid, exercise, iron, uric acid, oxidative stress, mitochondria

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