Effects of Different Doses of Antioxidant Intake on Exercise-Induced Oxidative Stress, Antioxidative Capacity and Inflammatory Responses

Abstract

Background

It is unknown whether an appropriate amount of exogenous antioxidant intake is present to maximize the exercise benefit on lifestyle-related diseases. The purpose of this study was to investigate the effects of two levels of exercise stress and exogenous antioxidant doses on exercise-induced oxidative stress, antioxidant capacity, and inflammatory response.

Methods

Wistar male rats were divided into two groups; sedentary (SED) and exercise (TR). The exercise was increased from 4 weeks of lower-load (90 min/week) to 4 weeks of higher-load (300 min/week). TR was subdivided into low (70 mg/kg: TR+N), medium (350 mg/kg: TR+VE-M), and high (700 mg/kg: TR+VE-H) according to the amount of vitamin E intake. Oxidative stress (d-ROMs), antioxidative capacity (BAP), and inflammatory response (hs-CRP: high sensitive C-reactive protein) were measured with blood samples before and after each exercise load PGC1-α was measured with muscle samples using real-time PCR.

Results

d-ROMs increased as exercise load was augmented in all TR and was higher in TR+N and TR+VE-M than in SED after higher-load exercise, while it was not different between SED and TR+VE-H. hs-CRP increased in TR+N and TR+VE-H after higher-load exercise as compared with before. PGC1-α increased only in TR+VE-M after higher-load exercise. CONCLUSIONSː Only medium doses of vitamin E intake may suppress the inflammatory response to oxidative stress during a large amount of exercise without inhibiting the expression of the transcription factor PGC1-α, suggesting the presence of an appropriate dose for exogenous antioxidant intake during exercise.

Keywords

Oxidative stress / Antioxidant capacity / Vitamin E supplementation / Exercise adaptations / Chronic inflammation / PGC-1α

References

[1] Alessio HM, Goldfarb AH. Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training. J Appl Physiol, 1988, 64(4): 1333-1336

[2] American Diabetes Association. Economic costs of diabetes in the U.S. in 2007. Diabetes Care. 2008;31(3):596–615. https://doi.org/10.2337/dc08-9017.

[3] Asbaghi O, Salehpour S, Rezaei Kelishadi M, Kashkooli S, Mansoori A, Nadery Dehuk ET, Nadery M, Mozaffari-Khosravi H. The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep., 2020, 10(1): 17499

[4] Barrera G, Pizzimenti S, Daga M, Dianzani C, Arcaro A, Cetrangolo GP, Giordano G, Cucci MA, Graf M, Gentile F. Lipid peroxidation-derived aldehydes, 4-hydroxynonenal and malondialdehyde in aging-related disorders. Antioxidants (Basel)., 2018, 78102

[5] Braun H, Koehler K, Geyer H, Kleiner J, Mester J, Schänzer W. Dietary supplement use among elite young German athletes. Int J Sport Nutr Exerc Metab., 2009, 19197-109

[6] Casuso RA, Al-Fazazi S, Hidalgo-Gutierrez A, López LC, Huertas JR. Hydroxytyrosol influences exercise-induced mitochondrial respiratory complex assembly into supercomplexes in rats. Free Radic Biol Med., 2019, 134: 304-310

[7] Casuso RA, Martínez-López EJ, Hita-Contreras F, Camiletti-Moirón D, Martínez-Amat A, Martínez-Romero E. Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats. Nutr Res., 2015, 35(7): 585-91

[8] Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem., 1987, 162(1): 156-9

[9] Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med., 2000, 29(8): 790-2

[10] Edgett BA, Foster WS, Hankinson PB, Simpson CA, Little JP, Graham RB, Gurd BJ. Dissociation of increases in PGC-1α and its regulators from exercise intensity and muscle activation following acute exercise. PLoS ONE., 2013, 8(8 e71623

[11] Fleige S, Pfaffl MW. RNA integrity and the effect on the real-time qRT-PCR performance. Mol Aspects Med., 2006, 272–3): 126-39

[12] Flockhart M, Nilsson LC, Tais S, Ekblom B, Apró W, Larsen FJ. Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers. Cell Metab., 2021, 33(5): 957-70

[13] Gomez-Cabrera MC, Salvador-Pascual A, Cabo H, Ferrando B, Vina J. Redox modulation of mitochondriogenesis in exercise. Does antioxidant supplementation blunt the benefits of exercise training?. Free Radic Biol Med, 2015, 86: 37-46

[14] Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Viña J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr., 2008, 87(1): 142-9

[15] Gonçalves NG, Cavaletti SH, Pasqualucci CA, Martins MA, Lin CJ. Fructose ingestion impairs expression of genes involved in skeletal muscle's adaptive response to aerobic exercise. Genes Nutr., 2017, 12: 33

[16] Gubler U, Hoffman BJ. A simple and very efficient method for generating cDNA libraries. Gene., 1983, 25(2–3): 263-9

[17] Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature., 2008, 454(7203): 463-9

[18] Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR. Genome Res., 1996, 6(10): 986-94

[19] Higashida K, Kim SH, Higuchi M, Holloszy JO, Han DH. Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab., 2011, 301(5): E779-84

[20] Ho SS, Dhaliwal SS, Hills AP, Pal S. The effect of 12 weeks of aerobic, resistance or combination exercise training on cardiovascular risk factors in the overweight and obese in a randomized trial. BMC Public Health., 2012, 12: 704

[21] Ito D, Cao P, Kakihana T, Sato E, Suda C, Muroya Y, Ogawa Y, Hu G, Ishii T, Ito O, Kohzuki M, Kiyomoto H. Chronic running exercise alleviates early progression of nephropathy with upregulation of nitric oxide synthases and suppression of glycation in Zucker diabetic rats. PLoS ONE., 2015, 10(9): e0138037

[22] Kim JC, Park GD, Kim SH. Inhibition of oxidative stress by antioxidant supplementation does not limit muscle mitochondrial biogenesis or endurance capacity in rats. J Nutr Sci Vitaminol (Tokyo)., 2017, 634277-83

[23] Kim K, Kim YH, Lee SH, Jeon MJ, Park SY, Doh KO. Effect of exercise intensity on unfolded protein response in skeletal muscle of rat. Korean J Physiol Pharmacol., 2014, 18(3): 211-6

[24] Kryściak K, Majerczak J, Kryściak J, Łochyński D, Kaczmarek D, Drzymała-Celichowska H, Krutki P, Gawedzka A, Guzik M, Korostynski M, Szkutnik Z, Pyza E, Jarmuszkiewicz W, Zoladz JA, Celichowski J. Adaptation of motor unit contractile properties in rat medial gastrocnemius to treadmill endurance training: Relationship to muscle mitochondrial biogenesis. PLoS ONE., 2018, 13(4 e0195704

[25] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods., 2001, 254): 402-8

[26] Luo M, Lu J, Li C, Wen B, Chu W, Dang X, He T, Meng X, Yang Y, Chen D. Hydrogen improves exercise endurance in rats by promoting mitochondrial biogenesis. Genomics., 2022, 114(6 110523

[27] Martin-Rubio AS, Sopelana P, Ibargoitia ML, Guillén MD. Prooxidant effect of α-tocopherol on soybean oil. Global monitoring of its oxidation process under accelerated storage conditions by 1H nuclear magnetic resonance. Food Chem., 2018, 245: 312-23

[28] McArdle A, Pattwell D, Vasilaki A, Griffiths RD, Jackson MJ. Contractile activity-induced oxidative stress: cellular origin and adaptive responses. Am J Physiol Cell Physiol., 2001, 2803): C621-7

[29] Merry TL, McConell GK. Do reactive oxygen species regulate skeletal muscle glucose uptake during contraction?. Exerc Sport Sci Rev., 2012, 40(2): 102-5

[30] Metin G, Atukeren P, Gümüştaş MK, Belce A, Kayserilioglu A. The effect of vitamin E treatment on oxidative stress generated in trained rats. Tohoku J Exp Med., 2002, 198(1): 47-53

[31] Michels AJ, Frei B. Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. Nutrients., 2013, 5(12): 5161-92

[32] Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res, 2003, 57: 861-868

[33] Mrakic-Sposta S, Gussoni M, Moretti S, Pratali L, Giardini G, Tacchini P, Dellanoce C, Tonacci A, Mastorci F, Borghini A, Montorsi M, Vezzoli A. Effects of mountain ultra-marathon running on ROS production and oxidative damage by micro-invasive analytic techniques. PLoS ONE., 2015, 10(11 e0141780

[34] Paulsen G, Hamarsland H, Cumming KT, Johansen RE, Hulmi JJ, Børsheim E, Wiig H, Garthe I, Raastad T. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol., 2014, 5928): 1887-901

[35] Petróczi A, Naughton DP, Pearce G, Bailey R, Bloodworth A, McNamee M. Nutritional supplement use by elite young UK athletes: fallacies of advice regarding efficacy. J Int Soc Sports Nutr., 2008, 5: 22

[36] Reichhold S, Neubauer O, Bulmer AC, Knasmüller S, Wagner KH. Endurance exercise and DNA stability: is there a link to duration and intensity?. Mutat Res, 2009, 682: 28-38

[37] Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA, 2009, 106(21): 8665-70

[38] Rius-Pérez S, Torres-Cuevas I, Millán I, Ortega ÁL, Pérez S. PGC-1 α, inflammation, and oxidative stress: an integrative view in metabolism. Oxid Med Cell Longev., 2020, 2020: 1452696

[39] Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, Barengo NC, Beaton AZ, Benjamin EJ, Benziger CP, Bonny A, Brauer M, Brodmann M, Cahill TJ, Carapetis J, Catapano AL, Chugh SS, Cooper LT, Coresh J, Criqui M, DeCleene N, Eagle KA, Emmons-Bell S, Feigin VL, Fernández-Solà J, Fowkes G, Gakidou E, Grundy SM, He FJ, Howard G, Hu F, Inker L, Karthikeyan G, Kassebaum N, Koroshetz W, Lavie C, Lloyd-Jones D, Lu HS, Mirijello A, Temesgen AM, Mokdad A, Moran AE, Muntner P, Narula J, Neal B, Ntsekhe M, Moraes de Oliveira G, Otto C, Owolabi M, Pratt M, Rajagopalan S, Reitsma M, Ribeiro ALP, Rigotti N, Rodgers A, Sable C, Shakil S, Sliwa-Hahnle K, Stark B, Sundström J, Timpel P, Tleyjeh IM, Valgimigli M, Vos T, Whelton PK, Yacoub M, Zuhlke L, Murray C, Fuster V. GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol., 2020, 76(25): 2982-3021

[40] Spanidis Y, Stagos D, Orfanou M, Goutzourelas N, Bar-Or D, Spandidos D, Kouretas D. Variations in oxidative stress levels in 3 days follow-up in ultramarathon mountain race athletes. J Strength Cond Res., 2017, 31(3): 582-94 https://www.nsca.com/

[41] Terada S, Tabata I. Effects of acute bouts of running and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle. Am J Physiol Endocrinol Metab., 2004, 286(2): E208-16

[42] Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med, 2011, 51: 1000-1013

[43] Trewin AJ, Lundell LS, Perry BD, Henríquez-Olguín C, Levinger I, McConell GK, Stepto NK. Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle. Am J Physiol Endocrinol Metab., 2015, 309(4): E388-97

[44] Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol., 2002, 3(7): research0034

[45] Venditti P, Napolitano G, Barone D, Di Meo S. Vitamin E supplementation modifies adaptive responses to training in rat skeletal muscle. Free Radic Res, 2014, 48: 1179-1189

[46] Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine V, Peppa M, Rayfield EJ. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci U S A., 2002, 99(24): 15596-601

[47] Warburton DER, Nicol CW, Bredin SSD. Health benefits of physical activity: the evidence. CMAJ, 2006, 174(6): 801-809

[48] Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 2004, 27: 1047-1053

[49] Wisløff U, Helgerud J, Kemi OJ, Ellingsen Ø. Intensity-controlled treadmill running in rats: VO₂max and cardiac hypertrophy. Am J Physiol Heart Circ Physiol., 2001, 280(3): H1301-10

[50] Wong ML, Medrano JF. Real-time PCR for mRNA quantitation. Biotechniques., 2005, 39: 75-85

[51] Yach D, Hawkes C, Gould CL, Hofman KJ. The global burden of chronic diseases: overcoming impediments to prevention and control. JAMA., 2004, 291: 2616-22

[52] Yang C, Jiao Y, Wei B, Yang Z, Wu JF, Jensen J, Jean WH, Huang CY, Kuo CH. Aged cells in human skeletal muscle after resistance exercise. Aging., 2018, 10: 1356-65

Funding

Japan Society for the Promotion of Science(22K11609)

RIGHTS & PERMISSIONS

Beijing Sport University