• Elucidating cylindrospermopsin toxicity via synthetic analogues: An in vitro approach

      Evans, DM; Hughes, J; Jones, LF; Murphy, PJ; Falfushynska, H; Horyn, O; Sokolova, IM; Christensen, J; Coles, SJ; Rzymski, P; et al. (Elsevier, 2019-06-10)
      © 2019 Elsevier Ltd Cylindrospermopsin (CYN) is an alkaloid biosynthesized by selected cyanobacteria, the cyto- and genotoxic properties of which have been studied extensively by in vitro and in vivo experimental models. Various studies have separately established the role of uracil, guanidine and hydroxyl groups in CYN-induced toxicity. In the present study, we have prepared five synthetic analogues that all possess a uracil group but had variations in the other functionality found in CYN. We compared the in vitro toxicity of these analogues in common carp hepatocytes by assessing oxidative stress markers, DNA fragmentation and apoptosis. All the analogues tested induced generation of reactive oxygen species, lipid peroxidation (LPO) and DNA fragmentation. However, the greatest increase in LPO and increase in caspase-3 activity, an apoptosis marker, was demonstrated by an analogue containing guanidine, hydroxyl and uracil functionalities similar to those found in CYN but lacking the complex tricyclic structure of CYN. We also report a crystal structure of an analogue lacking the hydroxyl group found in CYN which does not show intramolecular H-bonding interactions between the guanidine and the uracil functionalities. The observations made in this work supports the hypothesis that CYN toxicity is a result of an interplay between both of the uracil, hydroxyl and guanidine functional groups.
    • Enhanced erythrocyte antioxidant status following an 8-week aerobic exercise training program in heavy drinkers

      Georgakouli, K; Manthou, E; Fatouros, IG; Georgoulias, P; Deli, CK; Koutedakis, Y; Theodorakis, Y; Jamurtas, AZ; Department of Physical Education and Sport Science, University of Thessaly, Karies, Trikala 42100, Greece; Institute of Human Performance and Rehabilitation, Centre for Research and Technology - Thessaly (CERETETH), Karies, Trikala 42100, Greece. Electronic address: kgeorgakouli@gmail.com. (Elsevier BV, 2017-12-02)
      © 2017 Elsevier Inc. Alcohol-induced oxidative stress is involved in the development and progression of various pathological conditions and diseases. On the other hand, exercise training has been shown to improve redox status, thus attenuating oxidative stress-associated disease processes. The purpose of the present study was to evaluate the effect of an exercise training program that has been previously reported to decrease alcohol consumption on blood redox status in heavy drinkers. In a non-randomized within-subject design, 11 sedentary, heavily drinking men (age: 30.3 ± 3.5 years; BMI: 28.4 ± 0.86 kg/m2) participated first in a control condition for 4 weeks, and then in an intervention where they completed an 8-week supervised aerobic training program of moderate intensity (50–60% of the heart rate reserve). Blood samples were collected in the control condition (pre-, post-control) as well as before, during (week 4 of the training program), and after intervention (week 8 of the training program). Samples were analyzed for total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), uric acid (UA), bilirubin, reduced glutathione (GSH), and catalase activity. No significant change in indices of redox status in the pre- and post-control was observed. Catalase activity increased (p < 0.05) after 8 weeks of intervention compared to week 4. GSH increased (p < 0.05) after 8 weeks of intervention compared to the control condition and to week 4 of intervention. TAC, UA, bilirubin, TBARS, and PC did not significantly change at any time point. Moreover, concentrations of GSH, TBARS, and catalase activity negatively correlated with alcohol consumption. In conclusion, an 8-week aerobic training program enhanced erythrocyte antioxidant status in heavy drinkers, indicating that aerobic training may attenuate pathological processes caused by alcohol-induced oxidative stress.
    • Ergogenic and Antioxidant Effects of Spirulina Supplementation in Humans

      Kalafati, Maria; Jamurtas, Athanasios Z.; Nikolaidis, Michalis G.; Paschalis, Vassilis; Theodorou, Anastasios A.; Sakellariou, G. K.; Koutedakis, Yiannis; Kouretas, Dimitris (American College of Sports Medicine, 2010)
      Purpose: Spirulina is a popular nutritional supplement that is accompanied by claiMSS for antioxidant and performance-enhancing effects. Therefore, the aim of the present study was to examine the effect of spirulina supplementation on (i) exercise performance, (ii) substrate metabolism, and (iii) blood redox status both at rest and after exercise. Methods: Nine moderately trained males took part in a double-blind, placebo-controlled, counterbalanced crossover study. Each subject received either spirulina (6 gd-1) or placebo for 4 wk. Each subject ran on a treadmill at an intensity corresponding to 70%–75% of their VO2max for 2 h and then at 95% VO2max to exhaustion. Exercise performance and respiratory quotient during exercise were measured after both placebo and spirulina supplementation. Blood samples were drawn before, immediately after, and at 1, 24, and 48 h after exercise. Reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, thiobarbituric acid-reactive substances (TBARS), protein carbonyls, catalase activity, and total antioxidant capacity (TAC) were determined. Results: Time to fatigue after the 2-h run was significantly longer after spirulina supplementation (2.05 ± 0.68 vs 2.70 ± 0.79 min). Ingestion of spirulina significantly decreased carbohydrate oxidation rate by 10.3% and increased fat oxidation rate by 10.9% during the 2-h run compared with the placebo trial. GSH levels were higher after the spirulina supplementation compared with placebo at rest and 24 h after exercise. TBARS levels increased after exercise after placebo but not after spirulina supplementation. Protein carbonyls, catalase, and TAC levels increased similarly immediately after and 1 h after exercise in both groups. Conclusions: Spirulina supplementation induced a significant increase in exercise performance, fat oxidation, and GSH concentration and attenuated the exercise-induced increase in lipid peroxidation.
    • Uremic myopathy: Is oxidative stress implicated in muscle dysfunction in uremia?

      Kaltsatou, A; Sakkas, GK; Poulianiti, KP; Koutedakis, Y; Tepetes, K; Christodoulidis, G; Stefanidis, I; Karatzaferi, C; Department of Physical Education and Sport Sciences (DPESS), School of Physical Education (PE), University of Thessaly Trikala, Greece. (Frontiers Media SA, 2015-03-30)
      Renal failure is accompanied by progressive muscle weakness and premature fatigue, in part linked to hypokinesis and in part to uremic toxicity. These changes are associated with various detrimental biochemical and morphological alterations. All of these pathological parameters are collectively termed uremic myopathy. Various interventions while helpful can't fully remedy the pathological phenotype. Complex mechanisms that stimulate muscle dysfunction in uremia have been proposed, and oxidative stress could be implicated. Skeletal muscles continuously produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) at rest and more so during contraction. The aim of this mini review is to provide an update on recent advances in our understanding of how ROS and RNS generation might contribute to muscle dysfunction in uremia. Thus, a systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. While few studies met our criteria their findings are discussed making reference to other available literature data. Oxidative stress can direct muscle cells into a catabolic state and chronic exposure to it leads to wasting. Moreover, redox disturbances can significantly affect force production per se. We conclude that oxidative stress can be in part responsible for some aspects of uremic myopathy. Further research is needed to discern clear mechanisms and to help efforts to counteract muscle weakness and exercise intolerance in uremic patients.