Oxidative Stress and Antioxidants in Experimental Metabolic Syndrome

  • Matilde Otero-LosadaEmail author
  • Gabriel Cao
  • Hernán Gómez Llambí
  • Mariana H. Nobile
  • Francisco Azzato
  • José Milei
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 16)


Metabolic syndrome is a prevalent condition in Western and developing countries (20 to 30 % of adults) that represents a serious public health threat. One of the defects in metabolic syndrome and in its associated diseases such as hypertension, dislipemia, insulin resistance and obesity (mainly visceral), is the increase in general oxidative metabolism with development of oxidative stress. This implies the overproduction (and/or reduced degradation) of reactive oxygen species that usually overrides the physiological antioxidative defense. Thus, there is an increase in the oxidant-to-antioxidant compounds’ ratio. In this chapter, we comment and revise some of our evidence on this topic obtained in an experimental model of metabolic syndrome. In particular, we have found that chronic consumption of cola beverages, either sucrose- or artificially-sweetened cola, leads to a condition that reproduces the typical features of human metabolic syndrome. Following the characterization of our model, we have succeeded in replicating this model as shown in our first studies. Here we share some of the most important findings in relation with oxidative metabolism both general and tisular, with particular emphasis on hypertriglyceridemia, pancreatic and renal changes. Oxidative alterations and inflammatory mechanisms are concurrent in otherwise healthy young adult rats following cola beverage drinking for long periods.


Metabolic syndrome Hypertriglyceridemia Insulin resistance Oxidative stress Pancreas Kidneys Inflammation Thioredoxins 


  1. 1.
    Bonomini F, Rodella LF, Rezzani R (2015) Metabolic syndrome, aging and involvement of oxidative stress. Aging Dis 6:109–120CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Robberecht H, Hermans N (2016) Biomarkers of metabolic syndrome: biochemical background and clinical significance. Metab Syndr Relat Disord 14:47–93CrossRefPubMedGoogle Scholar
  3. 3.
    Grundy SM (2008) Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 28:629–636CrossRefPubMedGoogle Scholar
  4. 4.
    Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428CrossRefPubMedGoogle Scholar
  5. 5.
    Bulteau AL, Szweda LI, Friguet B (2006) Mitochondrial protein oxidation and degradation in response to oxidative stress and aging. Exp Gerontol 41:653–657CrossRefPubMedGoogle Scholar
  6. 6.
    Roberts CK, Sindhu KK (2009) Oxidative stress and metabolic syndrome. Life Sci 84:705–712CrossRefPubMedGoogle Scholar
  7. 7.
    Otero-Losada M, Grana DR, Müller A et al (2011) Lipid profile and plasma antioxidant status in sweet carbonated beverage-induced metabolic syndrome in rat. Int J Cardiol 146:106–109CrossRefPubMedGoogle Scholar
  8. 8.
    Milei J, Otero-Losada M, Gómez Llambí H et al (2011) Chronic cola drinking induces metabolic and cardiac alterations in rats. World J Cardiol 3:111–116CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Otero-Losada M, Loughlin SM, Rodríguez-Granillo G et al (2013) Metabolic disturbances and worsening of atherosclerotic lesions in ApoE−/− mice after cola beverages drinking. Cardiovasc Diabetol 12:57. doi: 10.1186/1475-2840-12-57 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Otero-Losada M, Cao G, Mc Loughlin S et al (2014) Rate of atherosclerosis progression in ApoE−/− mice long after discontinuation of cola beverage drinking. PLoS One 9:e89838CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Otero-Losada M, Cao G, González J et al (2015) Morphological changes in endocrine pancreas following cola drink consumption in rats. PLoS One 10:e0118700CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Otero-Losada M, González J, Ottaviano G et al (2016) Cardiorenal involvement in the metabolic syndrome induced by cola drinking in rats. Proinflammatory cytokines and impaired antioxidative protection. Mediators Inflamm 2016: 0000000 (in press)Google Scholar
  13. 13.
    Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4:600–609CrossRefPubMedGoogle Scholar
  14. 14.
    Miyamae T, Seki M, Naga T et al (2013) Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation. Redox Rep 18:12–19CrossRefPubMedGoogle Scholar
  15. 15.
    Tian G, Sawashita J, Kubo H et al (2014) Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice. Antioxid Redox Signal 20:2606–2620CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Lenaz G (1998) Role of mitochondria in oxidative stress and ageing. Biochim Biophys Acta 1366:53–67CrossRefPubMedGoogle Scholar
  17. 17.
    Lenaz G, Fato R, Castelluccio C et al (1993) The function of coenzyme Q in mitochondria. Clin Investig 71:S66–S70CrossRefPubMedGoogle Scholar
  18. 18.
    Tomasetti M, Littarru GP, Stocker R, Alleva R (1999) Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes. Free Radic Biol Med 27:1027–1032CrossRefPubMedGoogle Scholar
  19. 19.
    Aberg F, Appelkvist EL, Dallner G, Ernster L (1992) Distribution and redox state of ubiquinones in rat and human tissues. Arch Biochem Biophys 295:230–234CrossRefPubMedGoogle Scholar
  20. 20.
    Rossi DJ, Jamieson CH, Weissman IL (2008) Stems cells and the pathways to aging and cancer. Cell 132:681–696CrossRefPubMedGoogle Scholar
  21. 21.
    Fridovich I (2004) Mitochondria: are they the seat of senescence? Aging Cell 3:13–16CrossRefPubMedGoogle Scholar
  22. 22.
    Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13CrossRefPubMedGoogle Scholar
  23. 23.
    Chabi B, Ljubicic V, Menzies KJ et al (2008) Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell 7:2–12CrossRefPubMedGoogle Scholar
  24. 24.
    Finkel T, Deng CX, Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460:587–591CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bonomini F, Tengattini S, Fabiano A, Bianchi R et al (2008) Atherosclerosis and oxidative stress. Histol Histopathol 23:381–390PubMedGoogle Scholar
  26. 26.
    Wild S, Roglic G, Green A et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053CrossRefPubMedGoogle Scholar
  27. 27.
    Rochette L, Zeller M, Cottin Y, Vergely C (2014) Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 1840:2709–2729CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Matilde Otero-Losada
    • 1
    Email author
  • Gabriel Cao
    • 1
  • Hernán Gómez Llambí
    • 1
  • Mariana H. Nobile
    • 1
  • Francisco Azzato
    • 1
  • José Milei
    • 1
  1. 1.Institute of Cardiological Research (ININCA, UBA-CONICET), School of MedicineUniversity of Buenos Aires and National Research CouncilBuenos AiresArgentina

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